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  • 1.
    Aniansson Zdolsek, Helena
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Holt, Patrick G.
    TVW Telethon Institute for Child Health Research, Perth, Australia.
    Nilsson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Expression of the T–cell markers CD3, CD4 and CD8 in healthy and atopic Children during the first 18 months of life1999In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 119, no 1, p. 6-12Article in journal (Refereed)
    Abstract [en]

    Background: There is little information available about the development of T–cell immunity in healthy and atopic children. We have studied prospectively the mean fluorescence intensity of the T–cell receptor complex–associated CD3, CD4 and CD8 in relation to atopic family history (AFH) and the development of atopic disease.

    Methods: Children with a defined AFH (n = 172) were followed from birth to 18 months and the cumulative history of atopic disease was recorded. Blood samples were obtained at birth and at 18 months, and in a subgroup of 78 children also at 3, 6 and 12 months. Multicolour flow cytometry was used to analyse pan T–cells (CD3+CD45+CD14–), T–helper–(CD3+CD4+) and T–cytotoxic–(CD3+CD8+) cells.

    Results: At 18 months, 31 children were atopic and 118 non–atopic. Children who developed atopic disease had a higher CD4 expression (mean fluorescence intensity, MFI) on CD4+CD3+ lymphocytes at birth and at 3 months, particularly as compared with non–atopic children without AFH. Furthermore, the CD3 expression on CD3+CD45+CD14– lymphocytes increased more slowly with age in children with double atopic heredity, as compared with children with no or only one atopic family member.

    Conclusions: The higher expression of the CD4 receptor in early infancy in children who developed atopic disease compared with non–atopics suggests a delayed expression in T–helper cells. Children with a strong AFH had a slower increase in the expression of CD3, indicating a delayed T–cell maturation.

  • 2.
    Backteman, K
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ledent, E
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Transfusion Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Berlin, Gösta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Transfusion Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    A rapid and reliable flow cytometric routine method for counting leucocytes in leucocyte-depleted platelet concentrates2002In: Vox Sanguinis, ISSN 0042-9007, E-ISSN 1423-0410, Vol. 83, no 1, p. 29-34Article in journal (Refereed)
    Abstract [en]

    Background and Objectives: To ensure a proper quality control it is important to use a reliable method to count low numbers of leucocytes in leucocyte-reduced platelet concentrates (PCs). Materials and Methods: A modified flow cytometric method for counting low numbers of leucocytes, based on a reference population contained in tubes with an exact number of fluorescent beads and staining with propidium iodide was used. To increase the number of events, the original sample volume was increased. Results: There was a good correlation in the number of leucocytes (r = 0.99) between the modified flow cytometric method and microscopy of samples from unfiltered and expected numbers from serially diluted PCs. Samples from leucocyte-reduced PCs obtained by apheresis or filtered buffy coats showed no correlation between results from the modified flow cytometric method and microscopy (Nageotte). Conclusion: Counting by microscopy gave a lower number of leucocytes than the modified flow cytometric method when counting a low number of cells. However, analysis of the serially diluted PCs proved that the modified flow cytometric method was reliable and rapid, making it suitable for clinical routine use.

  • 3.
    Backteman, Karin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Biological and methodological variation of lymphocyte subsets in blood of human adults2007In: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 322, no 1-2, p. 20-27Article in journal (Refereed)
    Abstract [en]

    Although lymphocyte populations are often monitored over time, information about the biological variation over time is limited. Three-colour-flow cytometry was used to investigate the biological and methodological variation of lymphocyte populations in blood. Fifteen healthy individuals (11 females and 4 males) were longitudinally monitored for 2-8 years. Blood samples were drawn monthly when possible. In total, 493 observations were included. Absolute counts and proportions were determined for T-cells (CD3+), T-helper cells (CD3+ CD4+), cytolytic T-cells (CD3+ CD8+), B-cells (CD3- CD19+) and NK-cells (CD3- CD16+/56+). As to variation over the year, ANOVA testing showed only a minor monthly variation for absolute counts of the CD8+ population (p < 0.05) for October compared with June and July, whereas no significant differences were found for the other populations or in the proportions of lymphocyte subsets. Although lower than the longitudinal variation, the methodological variation, expressed as coefficient of variation (CV %), was in a similar range as the variation over time, indicating that the normal biological variation should not be overestimated, while the methodological inter-assay should be taken into consideration in longitudinal studies or monitoring of patients. © 2007 Elsevier B.V. All rights reserved.

  • 4.
    Berg, Göran
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Ekerfelt, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Hammar, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Lindgren, R
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology.
    Matthiesen, Leif
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Cytokine changes in postmenopausal women treated with estrogens: A placebo-controlled study2002Article in journal (Refereed)
    Abstract [en]

    Problem: Hormone replacement therapy (HRT) is being increasingly used in postmenopausal women. Sex steroids are known to affect the immune system in several ways, although this is mainly based on clinical observations and experimental studies. Method of study: We studied the in vivo effects of transdermal estrogens (50 ╡g 17 ▀-Estradiol/24 hr) on cytokine production in postmenopausal women. A total of 17 women were randomized to either placebo (n = 7) or active estrogen therapy (n = 10) for 14 weeks, with addition of oral medoxyprogesterone acetate 10 mg daily during the last 2 weeks in both groups. Secretion of the cytokines IFN-?, IL-4, IL-10 and IL-6 in blood mononuclear cells was determined, spontaneously and after stimulation with common vaccination antigens and mitogen, using the cell ELISA technique. Results: IL-6 production after stimulation with purified protein derivate (PPD) decreased in the estrogen treated group (P < 0.01). Mitogen-induced IL-6 production was reduced in the estrogen treated group in contrast to an increase in the placebo group, leading to a significant difference (P < 0.01) between the groups after 12 weeks of treatment. This difference was eliminated after an addition of progestagens for 2 weeks. No significant changes were noted for IFN-?, IL-4 or IL-10 in relation to estrogen or placebo treatment. Conclusions: In the present controlled study, the main in vivo effect of estrogens was a decrease in IL-6 production, indicating a possible beneficial effect of estrogen therapy.

  • 5.
    Borch, Kurt
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Grodzinsky, Ewa
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Petersson, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery.
    Jönsson, Kjell-Åke
    Mårdh, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Valdimarsson, Trausti
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology.
    Prevalence of coeliac disease and relations to Helicobacter pylori infection and duodenitis in a Swedish adult population sample: A histomorphological and serological survey2000In: InflammoPharmacology, ISSN 0925-4692, E-ISSN 1568-5608, Vol. 8, no 4, p. 341-350Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to determine the prevalence of coeliac disease and its relation to duodenitis, H. pylori infection and gastritis in a sample of the adult general population. Methods: A Swedish population sample of 482 subjects (aged 35 to 85 years) were examined with gastro-duodenoscopy with multiple biopsies taken. Circulating antibodies to endomycium, gliadin, and H. pylori were also determined. Results: Based on histomorphological findings, coeliac disease was evident in 9 of 482 subjects giving a prevalence of 1.9 [1.0-4.0, 95% confidence interval] percent. The prevalence of gastritis with or without H. pylori infection did not differ between subjects with and without coeliac disease. Considering subjects without coeliac disease, there was no difference in the serum levels of gliadin antibodies between those with and without duodenitis. However, subjects with positive H. pylori status had significantly higher levels of gliadin antibodies than those with negative H. pylori status. Conclusions: This study confirms that there is a relatively high prevalence of undiagnosed coeliac disease in Swedish adults. There was no association between coeliac disease and H. pylori infection or gastritis, although serum gliadin antibody levels were slightly increased in subjects with positive H. pylori status.

  • 6.
    Dahle, Charlotte
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Kvarnström, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Samuelsson, Margareta
    Neurology Unit, Örebro University Hospital, Sweden.
    Ernerudh, Jan
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Elevated number of cells secreting transforming growth factor β in Guillain-Barré syndrome2003In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 111, no 12, p. 1095-1104Article in journal (Refereed)
    Abstract [en]

    We used ELISPOT and cell ELISA to study secretion of IL-4, IFN-γ, TGF-β, IL-6, and TNF-α by circulating mononuclear cells during the course of Guillain-Barré syndrome (GBS). Compared to healthy controls, patients with GBS had higher numbers of TGF-β-secreting cells and the number of individuals with myelin-peptide-induced IL-4 and TGF-β secretion was higher in the GBS group. No significant differences were seen concerning the predominantly pro-inflammatory cytokines IFN-γ, IL-6 or TNF-α. Our findings indicate a down-regulatory role for TGF-β and IL-4 in GBS.

  • 7.
    Dahle, Charlotte
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    Skogh, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Åberg, A K
    Örebro.
    Jalal, A
    Örebro.
    Olcén, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Methods of choice for diagnostic antinuclear antibody (ANA) screening: Benefit of adding antigen-specific assays to immunofluorescence microscopy2004In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 22, no 3, p. 241-248Article in journal (Refereed)
    Abstract [en]

    Objectives. To evaluate and compare the performances of three enzyme-immunoassays (EIAs) and a double radial immunodiffusion (DRID) test in addition to immunofluorescence (IF) microscopy for routine laboratory screening of patient sera sent for antinuclear antibody (ANA) analysis. Methods. 3079 consecutive patient sera sent for routine testing of ANA were analysed by IF microscopy on HEp-2 cells (IF-ANA), three different ANA-EIAs, and a DRID test for antibodies against extractable nuclear antigens. The IF-ANA and DRID tests were regarded as reference methods. Results. By IF-ANA and/or DRID, 375 sera (12%) turned out ANA-positive. A further 171 sera (6%) were positive by EIA, but could not be confirmed either by IF microscopy or DRID. 32 of the 375 ANA-positive (9%) sera were negative by IF microscopy, but had precipitating antibodies against Ro/SS-A (52 and/or 60 kD). Conclusions. Different assays for ANA analysis give overlapping results to a certain extent, but are by no means interchangeable. Thus, different ANA tests reflect different aspects of these autoantibodies. The diagnostic utility of ANA testing still mainly refers to IF-microscopy and precipitin tests. IF-ANA should not be abandoned as the golden standard in clinical routine, until diagnostic and classification criteria for systemic lupus erythematosus and other systemic inflammatory autoimmune diseases have been revised. However, in addition we strongly advocate that a specific test for anti-Ro/SS-A antibodies is always included.

  • 8.
    Ekerfelt, Christina
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Andersson, M.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Olausson, Anna
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Bergström, S.
    Department of Microbiology, University of Umeå, Umeå, Sweden.
    Hultman, Per
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Mercury exposure as a model for deviation of cytokine responses in experimental Lyme arthritis: HgCl2 treatment decreases T helper cell type 1-like responses and arthritis severity but delays eradication of Borrelia burgdorferi in C3H/HeN mice2007In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 150, no 1, p. 189-197Article in journal (Refereed)
    Abstract [en]

    Lyme borreliosis is a complex infection, where some individuals develop so-called ‘chronic borreliosis’. The pathogenetic mechanisms are unknown, but the type of immune response is probably important for healing. A strong T helper cell type 1 (Th1)-like response has been suggested as crucial for eradication of Borrelia and for avoiding development of chronic disease. Many studies aimed at altering the Th1/Th2 balance in Lyme arthritis employed mice deficient in cytokine genes, but the outcome has not been clear-cut, due possibly to the high redundancy of cytokines. This study aimed at studying the importance of the Th1/Th2 balance in murine Borrelia arthritis by using the Th2-deviating effect of subtoxic doses of inorganic mercury. Ninety-eight C3H/HeN mice were divided into four groups: Borrelia-infected (Bb), Borrelia-infected exposed to HgCl2 (BbHg), controls exposed to HgCl2 alone and normal controls. Mice were killed on days 3, 16, 44 and 65 post-Borrelia inoculation. Arthritis severity was evaluated by histology, spirochaetal load determined by Borrelia culture, IgG2a- and IgE-levels analysed by enzyme-linked immunosorbemt assay (ELISA) and cytokine-secreting cells detected by enzyme-linked immunospot (ELISPOT). BbHg mice showed less severe histological arthritis, but delayed eradication of spirochaetes compared to Bb mice, associated with increased levels of IgE (Th2-induced) and decreased levels of IgG2a (Th1-induced), consistent with a Th2-deviation. Both the numbers of Th1 and Th2 cytokine-secreting cells were reduced in BbHg mice, possibly explained by the fact that numbers of cytokine-secreting cells do not correlate with cytokine concentration. In conclusion, this study supports the hypothesis that a Th1-like response is required for optimal eradication of Borrelia.

  • 9.
    Ekerfelt, Christina
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Dahle, Charlotte
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Weissert, R.
    Department of Medicine, Division of Neuroimmunology, Karolinska Institute, Stockholm, Sweden.
    Kvarnström, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Olsson, T.
    Department of Medicine, Division of Neuroimmunology, Karolinska Institute, Stockholm, Sweden.
    Ernerudh, Jan
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Transfer of myelin-specific cells deviated in vitro towards IL-4 production ameliorates ongoing experimental allergic neuritis2001In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 123, no 1, p. 112-118Article in journal (Refereed)
    Abstract [en]

    A causal role of IL-4 (Th2) production for recovery in experimental allergic neuritis (EAN) was indicated by experiments where Th1-like autoreactive cell populations, taken from the induction phase of the disease, were deviated to extensive secretion of IL-4 in a selective fashion, by ex vivo stimulation with autoantigen in the presence of IL-4. The deviated cells were adoptively transferred to EAN rats at a time just prior to the onset of clinical signs. This treatment ameliorated EAN compared with sham treatment. This therapeutic approach, with generation of autoreactive IL-4-secreting cells ex vivo followed by subsequent adoptive transfer, may become a new selective treatment of organ-specific autoimmune diseases since, in contrast to previous attempts, it is done in a physiological and technically easy way.

  • 10.
    Ekerfelt, Christina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Jönsson, Anna-Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Vrethem, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ärlehag, L
    Forsum, Urban
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Lyme borreliosis in Sweden - Diagnostic performance of five commercial Borrelia serology kits using sera from well-defined patient groups2004In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 112, no 1, p. 74-78Article in journal (Refereed)
    Abstract [en]

    Five commercial Borrelia serology kits available in Sweden were evaluated and compared for their diagnostic performance in sera from clinically well-characterized patient groups. With the clinically defined groups as the gold standard, i.e. without knowledge of antibody status in serum and cerebrospinal fluid, the diagnostic performance of the kits was compared and important differences in diagnostic usefulness were found. The kits from Abbot and DAKO, that often predict clinically relevant Borrelia infection and do not detect antibodies in sera from patients without strong suspicion of Borrelia infection, were considered the most useful in the population studied. This kind of validation study is an important part of good laboratory practice and should be performed by laboratories serving patient populations with varying endemicity of Borrelia.

  • 11.
    Ekerfelt, Christina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Jenmalm, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Detection of spontaneous and antigen-induced human interleukin-4 responses in vitro: Comparison of ELISPOT, a novel ELISA and real-time RT-PCR2002In: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 260, no 1-2, p. 55-67Article in journal (Refereed)
    Abstract [en]

    Interleukin-4 (IL-4) is an important T-helper cell type 2 (Th2) cytokine in man, driving Th2 polarisation and exerting the most antagonistic effects to the Th1 cytokine interferon-? (IFN-?). Nevertheless, few data on spontaneous and antigen-specific secretion of IL-4 in man are available, mainly due to difficulties in the detection of IL-4. In this study, we compared three assays that can detect antigen-induced IL-4 responses, ELISPOT, ELISA after blocking the IL-4 receptor during cell culture, and real-time reverse transcription polymerase chain reaction (RT-PCR). Spontaneous, antigen- and allergen-induced responses were analysed in peripheral blood mononuclear cells from three groups with different secretion patterns for IL-4: atopic individuals, nonatopic individuals and pregnant women. ELISPOT displayed the highest sensitivity and was the only assay that could detect spontaneous secretion of IL-4 in all analysed samples. The IL-4 receptor blocking ELISA was considered best for the detection of in vitro antigen- and allergen-induced responses, since the results obtained from the ELISPOT and real-time RT-PCR displayed lower specificity, possibly because of seemingly aberrant IL-4 responses in the group of pregnant women. The real-time RT-PCR for detection of IL-4 mRNA proved to be sensitive, but expression of IL-4 mRNA was not correlated with the secretion of IL-4.

  • 12.
    Ekerfelt, Christina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Svenvik, Maria
    Roberg, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Bergström, S.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    A symptomatic Borrelia-seropositive individuals display the same incidence of Borrelia-specific interferon-gamma (IFN-gamma)-secreting cells in blood as patients with clinical Borrelia infection.1999In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 115, p. 498-502Article in journal (Refereed)
  • 13.
    Ekerfelt, Christina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Jarefors, Sara
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    Tynngard, N
    Hedlund, M
    Sander, B
    Bergström, S
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Phenotypes indicating cytolytic properties of Borrelia-specific interferon-? secreting cells in chronic Lyme neuroborreliosis2003In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 145, no 1-2, p. 115-126Article in journal (Refereed)
    Abstract [en]

    The immuno-pathogenetic mechanisms underlying chronic Lyme neuroborreliosis are mainly unknown. Human Borrelia burgdorferi (Bb) infection is associated with Bb-specific secretion of interferon-? (IFN-?), which may be important for the elimination of Bb, but this may also cause tissue injury. In order to increase the understanding of the pathogenic mechanisms in chronic neuroborreliosis, we investigated which cell types that secrete IFN-?. Blood mononuclear cells from 13 patients with neuroborreliosis and/or acrodermatitis chronicum atrophicans were stimulated with Bb antigen and the phenotypes of the induced IFN-?-secreting cells were analyzed with three different approaches. Cells expressing CD8 or TCR?d, which both have cytolytic properties, were the main phenotypes of IFN-?-secreting cells, indicating that tissue injury in chronic neuroborreliosis may be mediated by cytotoxic cells.

  • 14.
    Ekerfelt, Christina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion.
    Masreliez, C
    Svenvik, M
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Roberg, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Antibodies and T-cell reactivity to Borrelia burgdorferi in an asymptomatic population: A study of healthy blood donors in an Inland town district in the South-East of Sweden2001In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 33, no 11, p. 806-808Article in journal (Refereed)
    Abstract [en]

    To address the issue of whether Borrelia infection can be asymptomatic, blood donors with no history of borreliosis (n = 408) were screened for antibodies against Borrelia burgdorferi. Seropositive individuals (n = 17) were further investigated with respect to Borrelia-specific T-cell reactivity, using an interferon-? ELISPOT assay. Anti-Borrelia antibodies as well as Borrelia-specific T-cell responses were evident in 9 asymptomatic donors, strongly supporting a current or previous asymptomatic Borrelia infection.

  • 15.
    Ekerfelt, Christina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Mathiesen, Leif
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Berg, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Th2-deviation of fetus-specific T cells1999In: Immunology today (Amsterdam. Regular ed.), ISSN 0167-5699, E-ISSN 1355-8242, Vol. 20, p. 534-534Article in journal (Refereed)
  • 16. Elkarim, RA
    et al.
    Mustafa, M
    Link, H
    Bakhiet, M
    Ekerfelt, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Vrethem, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Induction of neutralizing autoantibodies to interferon-gamma in patients with polyneuropathy.1999In: Human Antibodies, ISSN 1093-2607, E-ISSN 1875-869X, Vol. 9, p. 55-60Article in journal (Refereed)
  • 17.
    Eriksson, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology.
    Andersson, Carina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology.
    Ekerfelt, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Skogh, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Relationship between serum levels of IL-18 and IgG1 in patients with primary Sjögren's syndrome, rheumatoid arthritis and healthy controls2004In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 137, no 3, p. 617-620Article in journal (Refereed)
    Abstract [en]

    Primary Sjögren's syndrome (SS) is characterized by inflammation in salivary and lachrymal glands, with a local predominance of Th1-like cytokines, as well as the pleiotropic cytokine interleukin (IL) 18. High serum levels of polyclonal IgG are common, with a subclass imbalance in which IgG1 is increased and IgG2 is normal or low. IL-18 is also of pathogenetic importance in rheumatoid arthritis. In the present study we looked for any relationship between serum IL-18 as well as transforming growth factor (TGF) β1 versus IgA, IgM, and IgG subclass levels in SS (n = 16), rheumatoid arthritis (RA) (n = 15), and healthy controls (n = 15). SS was defined by the revised American-European classification criteria. IL-18 and TGF-β1 were analyzed with enzyme immunoassays (EIA), and IgG1, IgG2 and IgG3 by single radial immunodiffusion. In the composite group of RA, SS and normal controls, IgG1 and IL-18 were related (R = 0.52, P = 0.0005). No relation was found neither between IL-18 versus IgG2, IgG3 or IgA, nor between serum TGF-β1 versus any of the immunoglobulins. Since serum levels of IL-18 are related to serum IgG1, IL-18 may be of importance for IgG1 switch and/or release.

  • 18.
    Eriksson, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology.
    Andersson, Carina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology.
    Ekerfelt, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Skogh, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Sjögren´s syndrome with myalgia is associated with subnormal secretion of cytokines by peripheral blood mononuclear cells.2004In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 31, p. 729-735Article in journal (Refereed)
  • 19.
    Ernerudh, Jan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Berlin, Gösta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Transfusion Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ekerfelt, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    The use of cell products for treatment of autoimmune neuroinflammatory diseases2002In: Current Medicinal Chemistry, ISSN 0929-8673, E-ISSN 1875-533X, Vol. 9, no 16, p. 1497-1505Article in journal (Refereed)
    Abstract [en]

    Cell products are live cells that are given to patients in order to replace or modify the function of missing or dysfunctional cells. Progress in technology and in the understanding of pathobiology may lead to the use of cell products in many areas. This review outlines the use of cell products in the treatment of autoimmune diseases, with focus on neuroinflammatory diseases like multiple sclerosis. Treatment of autoimmune diseases should be selective and specific in order to avoid serious side effects. To achieve this, T lymphocyte regulation has been in focus for several immunomodulatory regimens. One area of great interest is the use of T cell vaccination, when autologous attenuated auto-reactive T cells are given to patients in order to initiate a specific immune response to the pathogenic T cell populations. Phopheresis may be an immunomudulatory treatment related to T cell vaccination. Another promising area involves ex-vivo alteration of the cytokine profile of harmful auto-reactive T cells. This can be achieved by genetic manipulation or by certain cytokine stimulations. A subsequent adoptive cell transfer will, by homing mechanisms, lead to at site specific delivery of the cells, which will have a local down-regulatory effect on the inflammatory process. Although unsolved questions regarding doses, timing, optimal preparing conditions and mechanisms still remain, both T cell vaccination and adoptive transfer of ex-vivo manipulated cytokine secreting cells have proven successful for treatment of neuroinflammation in experimental models. T cell vaccination was shown to be feasible in patients with multiple sclerosis, however, otherwise the experience in humans so far is limited.

  • 20.
    Ernerudh, Jan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Berlin, Gösta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Transfusion Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Samuelsson, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Effect of photopheresis on lymphocyte population in children with newly diagnosed type 1 diabetes2004In: Clinical and Diagnostic Laboratory Immunology, ISSN 1071-412X, Vol. 11, no 5, p. 856-861Article in journal (Refereed)
    Abstract [en]

    In recent years photopheresis has been claimed to be an effective form of immunomodulation. It has also been shown to have an effect on the disease process at the onset of type 1 diabetes. In a double-blind, placebo-controlled randomized study, we analyzed if the effect of photopheresis in children with newly diagnosed diabetes is related to changes in the balance of lymhocyte populations. We also analyzed if lymphocyte subsets were related to recent infection, mild or aggressive disease manifestations, heredity, or gender. Nineteen children received active treatment with photopheresis, while 21 children received sham pheresis (placebo group). No influence of a history of previous infection, heredity, or certain clinical parameters on lymphocyte subsets was found. At the onset of type 1 diabetes, girls showed a higher proportion and a larger number of T cells (CD3+) and T-helper cells (CD4+) and a higher proportion of naïve CD4 +CD45RA+ cells. In the placebo group, an increase in the number of subsets with the activated phenotype in both the CD4 (CD29 +) and the CD8 (CD11a+) compartments was noted during the course of the study. These changes did not occur in the photopheresis group. No relation between lymphocyte subsets and clinical outcome was found 1 year after the treatment with photopheresis. In conclusion, we found no major effect of photopheresis on lymphocyte populations in a group of children with newly diagnosed type 1 diabetes. However, in the placebo group the proportions of activated CD4 and CD8 cells increased over time. Since these changes did not occur in the actively treated group, our findings suggest that photopheresis may have some suppressive effects.

  • 21.
    Esamai, Fabian
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Cerebral malaria in children in the highlands of Kenya: Aspects of pathogenesis and clinical presentation2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Malaria affects over 300 million persons in the world each year with a mortality of close to 2 million. In developing countries malaria has been endemic in the lowlands for centuries with no occurrence in the highlands above 2000 metres above sea level. This pattern has changed over the last decade whereby malaria is occurs in epidemics with a high morbidity and mortality among the inhabitants of the highlands especially children and pregnant women. Eldoret and its environs in Kenya is a highland area with an altitude of 2300 metres above sea level where malaria was rare up to the late 1980s. Since 1988 malaria occurs in epidemics in this region with a high prevalence of severe malaria especially cerebral malaria(CM). This led to the conduct of stndies that fonn the basis of this thesis with the aim of delineating aspects of pathogenesis and the clinical presentation of CM in the Western highlands of Kenya.

    Materials and Methods: Cross sectional, retrospective and prospective studies were conducted to study the prevalence of malaria among inpatients at the Moi Teaching and Referral Hospital (MTRH); to describe the clinical presentation of CM in the highlands; to compare temperatures in CM and uncomplicated malaria(UM) cases and to assay the serum tumour necrosis factor alpha (TNFa) and transforming growth factor beta (TGF-13)1 levels in these patients.

    A total of 4 720 children were retrospectively and prospectively studied over an 18 month period (1991-1993) to establish the top 20 diseases at the MTRH. This was followed by a prospective study of 23 CM and 12 UM cases in 1997. All the presenting features of the cases with CM were tabulated on admission and analysed so as to establish the clinical presentation of CM in this region and compare this to the standard as described by the World Health Organisation (WHO). A comparison was made between the brain, core and skin temperatures of the CM and UM cases with normal children acting as controls.

    This was a follow up of a similar stndy in 1993 that compared core and skin temperatures between measles, CM and UM with normal children as controls. Serum TNF-a and TGF-131 levels were assayed and compared among the CM and UM patients in the 1997 study and included the assay of cerebrospinal (CSF) TNF-α and TGF-β1 in CM.

    Results and conclusions: Malaria accounted for 3 3% of all admissions over the study period with a case fatality rate of 2.2% and a mortality rate of 10.7%. Most children with CM were aged 3-10 years and were of good nutritional status. They presented in coma, with fever, headache, convulsions and hyperparasitaemia and with a short duration of illness of less than 3 days. Severe anaemia and hypoglycaemia were not common features. Malaria is the leading cause of morbidity in the children stndied. CM in the highlands presents as that seen among non-immunes. There were no differences in brain, core and skin temperatures between the CM and UM patients. The brain temperature was however always lower than core temperature even in normal controls with brain temperature having a positive correlation with core temperature as the body temperature rises. Thus, the role of fever in the pathogenesis of CM is still unclear The serum TNF-α and TGF-β1 levels were the same in UM and CM cases with TNF-α and TGF-β1 having an inverse relationship to each other. Patients with deeper levels of coma had higher levels of TNF-α and lower levels of TGF-β1.

    List of papers
    1. Paediatric morbidity and mortality at the Eldoret District Hospital, Kenya
    Open this publication in new window or tab >>Paediatric morbidity and mortality at the Eldoret District Hospital, Kenya
    1995 (English)In: East African Medical Journal, ISSN 0012-835X, Vol. 72, no 3, p. 165-169Article in journal (Refereed) Published
    Abstract [en]

    Over an 18 month period, there were 4,720 paediatric admissions at the Eldoret District Hospital in Western Kenya. The most frequent 20 diseases were identified and their respective case fatality rates calculated. Malaria was the most common cause for admission (33.0%) but the fourth most common cause of death with a case fatality rate of 2.2%. The overall mortality rate on the paediatric wards was 8.2% with 64.9% of the deaths occurring within the first 24 hours of hospitalization. Three-fourth of all admissions were due to four diseases: malaria, pneumonia, gastroenteritis and measles. Targeted interventional programmes aimed at these 4 diseases, coupled with a comprehensive primary health care system, would most likely result in much less morbidity and mortality for the children in the district. The systems for routinely collecting and storing medical records were found to be substandard, making it very difficult to accurately monitor morbidity and mortality.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-81403 (URN)7796768 (PubMedID)
    Available from: 2012-09-13 Created: 2012-09-13 Last updated: 2017-12-07Bibliographically approved
    2. Clinical presentation and diagnosis of cerebral malaria in children in the highlands of western Kenya
    Open this publication in new window or tab >>Clinical presentation and diagnosis of cerebral malaria in children in the highlands of western Kenya
    Show others...
    1999 (English)In: East African Medical Journal, ISSN 0012-835X, Vol. 76, no 2, p. 89-92Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND:

    The clinical presentation of cerebral malaria in children in the highlands has not been documented.

    OBJECTIVE:

    To describe the presentation of cerebral malaria in the age group one to twelve years.

    DESIGN:

    Prospective study conducted from May to September 1997, the rainy season during which malaria occurs in epidemics in the highlands of Kenya.

    SETTING:

    Paediatric wards of the Moi Teaching and Referral Hospital, Eldoret which is the Teaching Hospital for Moi University and the referral centre for surrounding districts of Western Kenya, with an altitude of over 2000 metres above sea level.

    PATIENTS:

    Twenty three consecutive children aged one to twelve years with cerebral malaria as defined by the WHO were studied. All children were treated with the standard quinine regimen for cerebral malaria.

    RESULTS:

    Majority of the children were six to ten years of age with 95.7% having a normal weight for age. 91.3%, 89.5% and 72.2% had fever, headache and convulsions respectively. 68.1% had a short duration of illness (less than three days) with only 9.5% presenting with hypoglycaemia. Severe anaemia was not observed but 72% had mild to moderate anaemia. Hyperparasitaemia (parasite counts greater than 100,000 per microlitre) was found in majority of the cases.

    CONCLUSION:

    Cerebral malaria presentation in the highlands is similar to that among non-immune populations and is an acute fulminant illness presenting with coma, hyperparasitaemia, fever and convulsions in children with normal nutritional status.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-81404 (URN)10442129 (PubMedID)
    Available from: 2012-09-13 Created: 2012-09-13 Last updated: 2017-12-07Bibliographically approved
    3. A comparison of core and skin temperature among normal and febrile children with cerebral malaria, uncomplicated malaria, and measles
    Open this publication in new window or tab >>A comparison of core and skin temperature among normal and febrile children with cerebral malaria, uncomplicated malaria, and measles
    Show others...
    1995 (English)In: Pathophysiology, ISSN 0928-4680, Vol. 2, no 1, p. 55-59Article in journal (Refereed) Published
    Abstract [en]

    Forty-four children were studied to compare the pathogenesis of fever in cerebral malaria, uncomplicated malaria and measles at the Eldoret District Hospital (EDH). A control group of normal children was used. The three patient groups were studied for three consecutive days measuring skin and core temperature three-times a day using the Liquid Crystal Device (LCD) thermometer. A statistical analysis of the results within and between the groups was carried out for core and skin temperature over the study period. No statistical differences were found between the groups for either the skin or the core temperature, but a significant statistical difference was demonstrated between the core and the skin temperature for all of the groups for each of the three days. No statistical difference was found when the differences between the core and skin temperature were compared between cerebral malaria and uncomplicated malaria. The possible roles of fever in morbidity and mortality are discussed, with special reference to cerebral malaria.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-81407 (URN)10.1016/0928-4680(94)00034-K (DOI)
    Available from: 2012-09-13 Created: 2012-09-13 Last updated: 2012-09-13Bibliographically approved
    4. A comparison of brain, core and skin temperature in children with complicated and uncomplicated malaria
    Open this publication in new window or tab >>A comparison of brain, core and skin temperature in children with complicated and uncomplicated malaria
    2001 (English)In: Journal of Tropical Pediatrics, ISSN 0142-6338, E-ISSN 1465-3664, Vol. 47, no 3, p. 170-175Article in journal (Refereed) Published
    Abstract [en]

    A prospective study was carried out in which brain, core and skin temperatures were studied in children with cerebral malaria (n = 23), uncomplicated malaria (n = 12) and normal children (n = 9) using the zero heat flow method. Patients with cerebral or uncomplicated malaria were admitted to the paediatric wards (mean age, 6 years 8 months ± 2 years 8 months). Normal children, children of the investigators, of the same age group, served as controls. Parasitaemia levels were similar in the cerebral and uncomplicated malaria cases. Higher brain than core temperatures would have been expected in cerebral malaria but not in uncomplicated malaria but this was not the case in this study. There was no statistical difference in brain, core and skin temperature between cerebral and uncomplicated malaria patients. However, there was a highly significant difference between normal children and cerebral and uncomplicated malaria patients. Brain temperature was 0.02–0.2°C below core temperature in all the groups with larger differences during the febrile period. Mean differences of brain minus core, brain minus skin and core minus skin between the two groups of patients were not statistically significant. There was no correlation between temperature and the level of coma or parasitaemia for cerebral and uncomplicated malaria patients. There was a positive correlation between brain and core temperature in both groups of patients during the febrile phase. Brain temperature remained lower than core temperature in cerebral and uncomplicated malaria as in normal children. Normal thermoregulation appears to be maintained in cerebral malaria.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25899 (URN)10.1093/tropej/47.3.170 (DOI)10340 (Local ID)10340 (Archive number)10340 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    5. Cerebral malaria in children: Serum and cerebrospinal fluid TNF-α and TGF-ß levels and their relationship to clinical outcome
    Open this publication in new window or tab >>Cerebral malaria in children: Serum and cerebrospinal fluid TNF-α and TGF-ß levels and their relationship to clinical outcome
    Show others...
    2003 (English)In: Journal of Tropical Pediatrics, ISSN 0142-6338, E-ISSN 1465-3664, Vol. 49, no 4, p. 216-223Article in journal (Refereed) Published
    Abstract [en]

    This was a prospective study conducted at the Moi Teaching and Referral Hospital, Eldoret, Kenya. Twenty‐three children admitted to the hospital with cerebral (CM) and 10 children with noncerebral malaria (NCM) were studied. The aim of the study was to establish and compare levels of tumour necrosis factor (TNF‐α) and transforming growth factor (TGF‐β1) in these children. Serum and cerebrospinal fluid (CSF) cytokine levels were assayed using ELISA kits. In serum, TGF‐β1 and TNF‐α decreased over 5 days after admission to the hospital in both groups of patients with CM and NCM. In the CSF of cerebral cases the levels of TNF‐α and TGF‐β1 were low and inversely related. Children in deeper coma had lower levels in serum of TGF‐β and higher levels of TNF‐α than those in lighter levels of coma. The serum TNF‐α levels in CM children were the same irrespective of the duration of illness before admission, but children with NCM who had been sick for a shorter duration before admission tended to have higher serum levels of TNF‐α and higher levels of TGF‐β than those with a longer duration of illness before admission. In conclusion, this study shows that TNF‐α and TGF‐β1 may not be useful in predicting the outcome for CM. They may, however, be useful in detecting children at risk of developing deep coma. TNF‐α and TGF‐β levels were inversely related both in serum and CSF.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-46358 (URN)10.1093/tropej/49.4.216 (DOI)
    Note

    On the day of the defence day the status of this article was submitted.

    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13Bibliographically approved
  • 22.
    Faresjö, Maria
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Berlin, Gösta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Transfusion Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Garcia, Jorge
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    The immunological effect of photopheresis in children with newly diagnosed type 1 diabetes2005In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 58, no 3, p. 459-466Article in journal (Refereed)
    Abstract [en]

    Photopheresis has been claimed to have immune-modulating effects, but the mechanisms of action are unknown. This study investigated the immune effect of photopheresis in children with type 1 diabetes, with a focus on the balance of Th1- and Th2-like cytokines. Ten children with newly diagnosed type 1 diabetes (10-17 y) were treated with five double treatments of photopheresis and 10 children matched for disease, age, and gender were given placebo tablets and sham pheresis. Expression of IFN-γ and IL-4 mRNA was determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and secretion of IFN-γ, IL-10, and IL-13 in cell-culture supernatants by ELISA after stimulation with glutamic acid decarboxylase (GAD65) (a.a. 247-279), the ABBOS peptide (a.a. 152-169), insulin, phytohemagglutinin (PHA), and keyhole limpet hemocyanin (KLH). Photopheresis changed antigen-stimulated immune balance in line with a Th2-like shift. Thus, the ratio of IFN-γ/IL-4 mRNA expression after in vitro stimulation with a peptide of the autoantigen GAD 65 was reduced after treatment in the photopheresis group. The IFN-γ/IL-4 mRNA expression ratio after in vitro stimulation with insulin was also lower in children treated with photopheresis compared with the placebo group. Photopheresis has an immune-modulating effect in children with type 1 diabetes, causing a Th2-like deviation. Copyright © 2005 International Pediatric Research Foundation, Inc.

  • 23.
    Faresjö, Maria
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Cytokine profile in children during the first 3 months after the diagnosis of type 1 diabetes2004In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 59, no 5, p. 517-526Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes is an autoimmune disease with an inflammatory process directed against the β cells in pancreas. This investigation aimed at studying the immune response during the first 3 months after the diagnosis of type 1 diabetes, with focus on the balance of T-helper 1 (Th1)- and Th2-like cytokines, produced spontaneously and in response to relevant autoantigens. Peripheral blood mononuclear cells (PBMCs) were collected from type 1 diabetic children (10-17 years) at 5, 20, 35 and 90 days after diagnosis. Expression of interferon-γ (IFN-γ) and interleukin-4 (IL-4) mRNA were detected by real-time reverse transcriptase polymerase chain reaction and IFN-γ, IL-10 and IL-13 by enzyme-linked immunosorbent assay in cell supernatant after stimulation with a glutamic acid decarboxylase 65 (GAD65)-peptide [amino acid (a.a.) 247-279], insulin, the ABBOS-peptide (a.a. 152-169), phytohaemagglutinin and keyhole limpet haemocyanin. Spontaneous and antigen-induced expression and secretion of cytokines were low at the diagnosis of type 1 diabetes. During the first month, after diagnosis, the GAD 65-peptide caused an increased ratio of IFN-γ/IL-4 mRNA expression (P < 0.05) and increased secretion of IFN-γ (P = 0.07). Expression of IFN-γ mRNA did also increase from stimulation with insulin (P < 0.05), even though cytokine secretion remained low. Thus, duration after diagnosis as well as metabolic state should be carefully considered both in studies of the pathogenesis of type 1 diabetes and in immune intervention studies at onset.

  • 24. Forsey, RJ
    et al.
    Thompson, JM
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Hurst, TL
    Strindhall, J
    Johansson, B
    Nilsson, B-O
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases.
    Wikby, A
    Plasma cytokine profile in elderly humans.2003In: Mechanisms of Ageing and Development, ISSN 0047-6374, E-ISSN 1872-6216, Vol. 124, p. 487-493Article in journal (Refereed)
  • 25.
    Garvin, Peter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Division of Preventive and Social Medicine and Public Health Science.
    Jonasson, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Carstensen, John
    Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Department of Health and Society, Tema Health and Society.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Kristenson, Margareta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Division of Preventive and Social Medicine and Public Health Science. Östergötlands Läns Landsting, Centre for Public Health Sciences, Centre for Public Health Sciences.
    Levels of circulating matrix metallo proteinase-9 is associated to psychosocial factors and lifestyle2006In: XIV International Symposium on Atherosclerosis,2006, 2006Conference paper (Other academic)
  • 26.
    Gati, Istvan
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Danielsson, Olof
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Betmark, T
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Öllinger, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Dizdar Segrell, Nil
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurology. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Effects of inhibitors of the arachidonic acid cascade on primary muscle culture from a Duchenne muscular dystrophy patient2007In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 77, no 3-4, p. 217-223Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to elucidate the mechanisms of action for potential targets of therapeutic intervention related to the arachidonic acid cascade in muscular dystrophy. Primary cultures from a Duchenne patient were used to study the expression of dystrophin-1, utrophin, desmin, neonatal myosin heavy chain (MHCn) and Bcl-2 during inhibition of phospholipase A2 (PLA2), cyclooxygenase (COX) and lipoxygenase (LOX). Hypo-osmotic treatment was applied in order to trigger Ca2+ influx and PLA2 activity. Inhibition of PLA2 and LOX with prednisolone and nordihydroguaiaretic acid (NDGA) caused a semi-quantitative increase of utrophin and Bcl-2-, and a dose-dependent, quantitative increase of desmin expression, an effect that was augmented by hypo-osmotic treatment. Our results indicate that LOX inhibitors, similarly to corticosteroids, can be beneficial in the treatment of muscular dystrophies. © 2007 Elsevier Ltd. All rights reserved.

  • 27.
    Gredmark, Sara
    et al.
    Karolinska Institutet.
    Jonasson, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Van Gosliga, Djoke
    Karilinska Institutet.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Söderberg-Nauclér, Cecilia
    Karolinska Institutet.
    Active cytomegalovirus replication in patients with coronary disease2007In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 41, no 4, p. 230-234Article in journal (Refereed)
    Abstract [en]

    Objectives. To study the prevalence of active cytomegalovirus (CMV) infection in patients with stable and unstable conditions of coronary artery disease (CAD). Design. Forty patients with acute coronary syndrome (ACS), 50 patients with stable angina and angiographically verified CAD (SA) and 50 clinically healthy controls were included. Monocytes were isolated from peripheral blood and CMV-RNA expression was determined by a nested RT-PCR assay. CMV IgM and IgG antibodies, interleukin-(IL)-6, IL-10 and CRP were measured in serum. Results. The prevalence of active CMV infection was significantly higher in patients with ACS (15%) and in patients with SA (10%) compared with controls (2%) (p < 0.001). The presence of an active CMV infection was associated with increased serum concentrations of IL-6. Conclusions. Active CMV infection was found to a larger extent in CAD patients than in healthy controls. The data indicate that CAD patients are more susceptible to reactivation of CMV and put new focus on the role of CMV in atherosclerosis.

  • 28.
    Grodzinsky, Ewa
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Andersson, C
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Comparative evaluation of serological tests for celiac disease: A European initiative toward standardization.2000In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 31, p. 513-519Article in journal (Refereed)
  • 29.
    Grodzinsky, Ewa
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ivarsson, A
    Juto, P
    Olcén, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment.
    Fälth-Magnusson, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Persson, L.Å.
    Hernell, O
    New automated immunoassay measuring immunoglobulin A antigliadin antibodies for prediction of celiac disease in childhood.2001In: Clinical and Diagnostic Laboratory Immunology, ISSN 1071-412X, Vol. 8, p. 564-570Article in journal (Refereed)
  • 30.
    Grusell, Mattias
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases.
    Widhe, Mona
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Increased expression of the Th1-inducing cytokines interleukin-12 and interleukin-18 in cerebrospinal fluid but not in sera from patients with Lyme neuroborreliosis2002In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 131, no 1-2, p. 173-178Article in journal (Refereed)
    Abstract [en]

    Lyme neuroborreliosis is a complex disease with different clinical outcomes and where immunopathological mechanisms are probably involved. In this study, sera and cerebrospinal fluid (CSF) from 21 neuroborreliosis patients and 26 control patients were analyzed for the Th1-inducing cytokines, interleukin (IL)-12 and IL-18, and the Th2 associated, soluble CD30 (sCD30) by ELISA. The results showed an increased number of neuroborreliosis patients expressing IL-12 (p<0.05) and IL-18 (p<0.05) in the CSF when compared with the controls, but no indication of increased levels in the sera. Nor were there any differences regarding levels of sCD30 in the sera or the CSF, indicating a local Th1-generating milieu in the target organ of neuroborreliosis.

  • 31.
    Hallin, Elisabeth
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    Mellergård, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurology. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Vrethem, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurology. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ekerfelt, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    In vitro Th2 deviation of myelin-specific peripheral blood lymphocytes from patients with multiple sclerosis2006In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 171, no 1-2, p. 156-162Article in journal (Refereed)
    Abstract [en]

    This study aimed at investigating if selective ex vivo immune deviation of myelin-specific cytokine secretion towards Th2 is possible in blood cells from patients with multiple sclerosis (MS). Interleukin (IL)-4 (Th2) and interferon-γ (Th1) secreting cells were recorded by ELISPOT in 13 MS patients. Deviation was successful in 10 patients. Interleukin-4 alone was most effective in inducing myelin-specific immune deviation in MS patients whereas IL-1 or IL-15 in combination with IL-4 did not improve the results. Further studies and improvements are needed before ex vivo immune deviation can be considered a potential treatment in patients with MS. © 2005 Elsevier B.V. All rights reserved.

  • 32.
    Håkansson, L.
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Adell, Gunnar
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Boeryd, B.
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Sjögren, F.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Sjödahl, R.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis1997In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 75, no 3, p. 374-380Article in journal (Refereed)
    Abstract [en]

    Local immunoregulation mediated by mononuclear tumour-infiltrating cells is considered of importance for tumour progression of colorectal cancer, although the balance between immunosuppressor and cytotoxic activities is unclear. Colorectal cancers from 26 patients were investigated using a panel of monoclonal antibodies in order to identify subsets of mononuclear inflammatory cells and to study their pattern of distribution in relation to tumour stage and cytotoxic immune reactivity against the tumour. In all but five tumours, mononuclear cells, lymphocytes or monocytes were present in fairly large numbers, particularly in the stroma. The infiltration of CD4+ mononuclear cells predominated over the CD8+ subset. Infiltration near the tumour cells was found in four cancers only. Stromal infiltration of CD11c+ macrophages was found in all but eight tumours. Small regressive areas, in which the histological architecture of the tumours was broken down, were found in 17 tumours with intense or moderate infiltration by CD4+ lymphocytes or CD11c+ macrophages. Probably this destruction of tumour tissue was caused by cytotoxic activity of the tumour-infiltrating mononuclear cells. In Dukes' class A and B tumours, CD4+ lymphocytes predominated over CD4+ cells with macrophage morphology, but the latter were increasingly found in Dukes' class C and D disease. The occurrence of MHC II-positive macrophages and lymphocytes in different Dukes' classes was similar to that of CD4+ cells. In contrast to this, CD11c+ and CD11a+ cells were more frequent in Dukes' A and B class tumours compared with Dukes' C and D. Four out of nine tumours of the latter stages showed a poor inflammatory reaction. The interpretation of our results is that the subsets of tumour-infiltrating mononuclear cells change with advancing Dukes' class and that the local immune control is gradually broken down in progressive tumour growth, even if some cytotoxic activity is still present.

  • 33.
    Jablonowska, Barbara
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Recurrent spontaneous abortion: a clinical, immunological and genetic study2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Recurrent spontaneous abortion (RSA) is defined as the loss of three or more consecutive pregnancies before 20 completed gestational weeks. The condition affects 0.5-1% of all women. In the majority of women with RSA, the cause remains unexplained after genetic, endocrine, immunological and anatomical investigations of the couple. However, there is increasing evidence that immunological mechanisms might contribute in the pathogenesis of RSA. Therefore high doses of intravenous immunoglobulin (IVIG), known to modulate immune responses, has been suggested as a treatment of RSA. The aim of this study was to evaluate IVIG in the treatment of RSA, and to elucidate immunological and genetic mechanisms behind this condition. In a prospective, double blind, placebo-controlled IVIG study we investigated 41 women with a history of unexplained RSA. They received 20g IVIG or placebo-saline every 3 weeks on five occasions from 6-7 gestational weeks. The overall success rate was 77% in the IVIG group compared with 79% in the placebo group, indicating that IVIG was not better than placebo and that both groups had better results than the predicted outcome.

    We also investigated the presence of blocking effect of maternal serum in a mixed leukocyte culture (MLC). Blood samples were obtained before and after pregnancy in the IVIG/placebo groups. As RSA controls we used 31 RSA women who did not achieve pregnancy during this study and were not enrolled in the IVIG study. As normal controls we used 10 non-pregnant women without a history of spontaneous abortions. Blocking antibodies were present in 20% of women with unexplained RSA and in 30% of the control group. The blocking effect before pregnancy was the same for IVIG-, placebo-, and untreated RSA controls as well as in the normal controls. We found no significant differences in blocking effect before compared with after IVIG or placebo treatment.

    We measured lymphocyte subset distributions in blood samples obtained in the first trimester and after pregnancy in 39 RSA women in the IVIG study and compared them with previous results from pregnant and non-pregnant controls. In the first trimester of pregnancy, the RSA women had significantly increased proportions ofB-cells (CD19), T cells subsets including activated HLA-DR expressing T cells (CD3+HLA-DR+), and T killer/effector cells (CD+S6F1+). The proportion of T suppressor/inducer cells (CD4+CD45RA+) was significantly decreased. Thus, in early pregnancy the immune system seems to be activated in RSA patients in contrast to the suppression noted in normal pregnancy. These changes in subpopulations do, however, not correlate to the outcome of pregnancy.

    We studied the compatibility of HLA-DRB1 alleles in the couples with unexplained RSA and the frequency of HLA-DRB1 and HLA-G alleles in these couples compared with fertile controls. We did not find significantly increased sharing of HLA-DRB1 alleles between partners. We found no significant differences for HLA-DRB1 and HLA-G allele frequencies in RSA couples compared with fertile controls.

    In conclusion, RSA patients have no genetic differences, their immune reaction during pregnancy is altered, their levels of blocking antibodies is of no use to predict pregnancy outcome and intravenously given high dose IVIG does not effect their pregnancy outcome.

    List of papers
    1. Prevention of recurrent spontaneous abortion by intravenous immunoglobulin: a double-blind placebo-controlled study
    Open this publication in new window or tab >>Prevention of recurrent spontaneous abortion by intravenous immunoglobulin: a double-blind placebo-controlled study
    Show others...
    1999 (English)In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 14, no 3, p. 838-841Article in journal (Refereed) Published
    Abstract [en]

    The aim of this study was to evaluate the therapeutic efficacy of intravenous immunoglobulin (IVIG) in the prevention of recurrent spontaneous abortion (RSA). In a double-blind, randomized, placebo-controlled study, 41 women with a history of unexplained recurrent spontaneous abortion were treated with IVIG or saline infusions during pregnancy. The birth of a child was considered a successful outcome. The overall success rate was 77% in the IVIG group compared with 79% in the placebo group. For women with primary RSA the success rates were 82 (IVIG) and 89% (placebo), and for women with secondary RSA the rates were 73 (IVIG) and 70% (placebo). We found no statistically significant difference in treatment results between IVIG and placebo.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25896 (URN)10.1093/humrep/14.3.838 (DOI)10337 (Local ID)10337 (Archive number)10337 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    2. Blocking antibodies in blood from patients with recurrent spontaneous abortion in relation to pregnancy outcome and intravenous immunoglobulin treatment
    Open this publication in new window or tab >>Blocking antibodies in blood from patients with recurrent spontaneous abortion in relation to pregnancy outcome and intravenous immunoglobulin treatment
    Show others...
    2001 (English)In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 45, no 4, p. 226-231Article in journal (Refereed) Published
    Abstract [en]

    PROBLEM: To study whether the occurrence of mixed lymphocyte culture (MLC) blocking antibodies is associated with pregnancy outcome in women with unexplained recurrent spontaneous abortion (RSA) and the in vivo effect of intravenous immunoglobulin (IVIG) treatment on MLC blocking effect.

    METHOD OF STUDY: Blood samples from 41 RSA patients were obtained before and after pregnancy, and blocking antibodies were estimated by one-way MLC assay. The patients received IVIG or placebo (saline) during pregnancy. Additionally, pre-pregnancy blood samples from 31 RSA women and 10 controls were obtained.

    RESULTS: We found no correlation between blocking antibodies before pregnancy and the pregnancy outcome. The occurrence of blocking antibodies was not affected by pregnancy or IVIG treatment.

    CONCLUSIONS: Blocking antibodies have no predictive value for the pregnancy outcome in RSA patients, and their production seems not to be affected by IVIG.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25897 (URN)10.1111/j.8755-8920.2001.450405.x (DOI)10338 (Local ID)10338 (Archive number)10338 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    3. T and B lymphocyte subsets in patients with unexplained recurrent spontaneous abortion: IVIG versus placebo treatment
    Open this publication in new window or tab >>T and B lymphocyte subsets in patients with unexplained recurrent spontaneous abortion: IVIG versus placebo treatment
    Show others...
    2002 (English)In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 48, no 5, p. 312-318Article in journal (Refereed) Published
    Abstract [en]

    Jablonowska B, Palfi M, Matthiesen L, Selbing A, Kjellberg S, Ernerudh J. T and B Lymphocyte subsets in patients with unexplained recurrent spontaneous abortion: IVIG versus placebo treatment. AJRI 2002; 48:312–318 © Blackwell Munksgaard, 2002

    PROBLEM: To investigate circulating lymphocyte subsets in women with recurrent spontaneous abortion (RSA) in relation to pregnancy outcome and to treatment with intravenous immunoglobulin (IVIG).

    METHOD OF STUDY: Forty-one women with a history of unexplained RSA were examined during first trimester of pregnancy before IVIG or placebo treatment and after pregnancy. The results were compared with five healthy, non-pregnant women and five women in the first trimester of normal pregnancy. Circulating lymphocyte subsets with focus on T-cell subpopulations were determined by flow cytometry.

    RESULTS:  The proportions of human leukocyte antigen (HLA)-DR positive T cells (CD3+ HLA-DR+), T-killer/effector cells (CD8+ S6F1+) and B cells (CD19+) were increased, whereas the proportion of T-suppressor/inducer cells (CD4+ CD45RA+) was decreased during first trimester pregnancy of RSA women compared with pregnant normal controls. T and B lymphocyte subsets did not correlate with pregnancy outcome on either IVIG or placebo group.

    CONCLUSIONS: In RSA patients, the immune system seems to be activated in contrast to the suppression noted in normal pregnancy.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26434 (URN)10.1034/j.1600-0897.2002.01010.x (DOI)10977 (Local ID)10977 (Archive number)10977 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    4. Analyses of human leukocyte antigen (HLA-DRB1 and HLA-G alleles in couples with unexplained recurrent spontaneous abortion: typing by using the Polymerase Chain Reaction method
    Open this publication in new window or tab >>Analyses of human leukocyte antigen (HLA-DRB1 and HLA-G alleles in couples with unexplained recurrent spontaneous abortion: typing by using the Polymerase Chain Reaction method
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Increased parental Human Leukocyte Antigen (HLA) sharing has been repmted in couples witb history of unexplained recurrent spontaneous abmtion (RSA). Parental HLA sharing increases the risk of feto-matemal histo-compatibility and potentially affects maternal alia-recognition of the fetus. HLA-G is expressed on trophoblast and is expected to play an important role during placental and fetal development. The aim of the present study was to investigate the compatibility of HLA-DRB1 alleles in the couples with unexplained RSA and to investigate the frequency of HLA-DRB1 alleles and HLA-G alleles in these couples compared with fertile controls.

    Methods: The frequency of HLA-DRB1 alleles in 36 couples with unexplained recurrent spontaneous abmtion, and the compatibility of HLA-DRB1 alleles between patient couples were studied using a polymerase chain reaction-sequence specific primers (PCR- SSP) method. The frequency of HLA-G alleles in 35 couples were studied using a polymerase chain reaction - single nuclotide polymorphism (PCR-SNP). As controls we used 40 fertile couples who were typed for HLA-DRB1 and HLA-G alleles.

    Results: There were no significant differences for HLA-DRB1 and HLA-G allele frequencies in RSA couples compared with fertile controls. There was no significant HLA-DRB1 allele sharing between the RSA couples and fertile controls.

    Conclusions: There is no higher HLA-DRB1 allele sharing in couples with unexplained RSA than in fettile couples. The association on allelic level between RSA and HLA-G gene was not supported by our data.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84516 (URN)
    Available from: 2012-10-11 Created: 2012-10-11 Last updated: 2012-10-11Bibliographically approved
  • 34.
    Jablonowska, Barbara
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Palfi, Miodrag
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Kjellberg, Svante
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Selbing, Anders
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Blocking antibodies in blood from patients with recurrent spontaneous abortion in relation to pregnancy outcome and intravenous immunoglobulin treatment2001In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 45, no 4, p. 226-231Article in journal (Refereed)
    Abstract [en]

    PROBLEM: To study whether the occurrence of mixed lymphocyte culture (MLC) blocking antibodies is associated with pregnancy outcome in women with unexplained recurrent spontaneous abortion (RSA) and the in vivo effect of intravenous immunoglobulin (IVIG) treatment on MLC blocking effect.

    METHOD OF STUDY: Blood samples from 41 RSA patients were obtained before and after pregnancy, and blocking antibodies were estimated by one-way MLC assay. The patients received IVIG or placebo (saline) during pregnancy. Additionally, pre-pregnancy blood samples from 31 RSA women and 10 controls were obtained.

    RESULTS: We found no correlation between blocking antibodies before pregnancy and the pregnancy outcome. The occurrence of blocking antibodies was not affected by pregnancy or IVIG treatment.

    CONCLUSIONS: Blocking antibodies have no predictive value for the pregnancy outcome in RSA patients, and their production seems not to be affected by IVIG.

  • 35.
    Jablonowska, Barbara
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Palfi, Miodrag
    Linköping University, Department of Molecular and Clinical Medicine, Transfusion Medicine. Linköping University, Faculty of Health Sciences.
    Matthiesen, Leif
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Selbing, Anders
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Kjellberg, Svante
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    T and B lymphocyte subsets in patients with unexplained recurrent spontaneous abortion: IVIG versus placebo treatment2002In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 48, no 5, p. 312-318Article in journal (Refereed)
    Abstract [en]

    Jablonowska B, Palfi M, Matthiesen L, Selbing A, Kjellberg S, Ernerudh J. T and B Lymphocyte subsets in patients with unexplained recurrent spontaneous abortion: IVIG versus placebo treatment. AJRI 2002; 48:312–318 © Blackwell Munksgaard, 2002

    PROBLEM: To investigate circulating lymphocyte subsets in women with recurrent spontaneous abortion (RSA) in relation to pregnancy outcome and to treatment with intravenous immunoglobulin (IVIG).

    METHOD OF STUDY: Forty-one women with a history of unexplained RSA were examined during first trimester of pregnancy before IVIG or placebo treatment and after pregnancy. The results were compared with five healthy, non-pregnant women and five women in the first trimester of normal pregnancy. Circulating lymphocyte subsets with focus on T-cell subpopulations were determined by flow cytometry.

    RESULTS:  The proportions of human leukocyte antigen (HLA)-DR positive T cells (CD3+ HLA-DR+), T-killer/effector cells (CD8+ S6F1+) and B cells (CD19+) were increased, whereas the proportion of T-suppressor/inducer cells (CD4+ CD45RA+) was decreased during first trimester pregnancy of RSA women compared with pregnant normal controls. T and B lymphocyte subsets did not correlate with pregnancy outcome on either IVIG or placebo group.

    CONCLUSIONS: In RSA patients, the immune system seems to be activated in contrast to the suppression noted in normal pregnancy.

  • 36.
    Jansson, A.
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Kvarnström, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Vrethem, Magnus
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Department of Neuroscience and Locomotion, Neurophysiology.
    Elispot assay detection of cytokine secretion in multiple sclerosis patients treated with interferon-β1a or glatiramer acetate compared with untreated patients2003In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 9, no 5, p. 440-445Article in journal (Refereed)
    Abstract [en]

    The mechanisms behind the beneficial effects of interferon-β1a (IFN-β1a) and glatiramer acetate (GA) in the treatment of multiple sclerosis (MS) are still uncertain. Altered cytokine patterns have been suggested including inhibition of proinflammatory cytokines like interferon-γ (IFN-γ) and enhancement of anti-inflammatory cytokines such as interleukin-4 (IL-4). Twenty-nine patients with MS (10 untreated, nine treated with IFN-β1a and 10 with GA) were investigated with elispot of peripheral blood mononuclear cells. Spontaneous and myelin induced (myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG)-14-39 and MOG 63-87) IFN-γ, IL-4, IL-5 and IL-10 secretion was studied. We found a significant reduction of spontaneous IFN-γ, IL-4 and IL-5, but no difference in IL-10 secreting cells in both groups of treated patients compared with the untreated patients. Myelin-specific responses showed a significant decrease of IFN-γ and an increase of IL-5, but no change in IL-4 and IL-10 secreting cells in treated compared with untreated patients. Both treatment groups revealed similar cytokine secretion patterns except for a more pronounced decrease of both spontaneous and MOG 14-39 induced IL-4 secretion in the IFN-β1a treated group. Thus, immunological effects of IFN-β1a and GA were similar showing that disease promoting Th1 (IFN-γ) cells were reduced while the potentially beneficial Th2 response (IL-4) was maintained.

  • 37.
    Jonasson, Lena
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Backteman, Karin
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Loss of natural killer cell activity in patients with coronary artery disease2005In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 183, no 2, p. 316-321Article in journal (Refereed)
    Abstract [en]

    Background:: Natural killer (NK) cells are important components of the innate immune system and have a potential role in the regulation of autoimmunity. In the present study, we evaluated the NK cells in patients with coronary artery disease (CAD) and related the findings to clinical and laboratory parameters of the disease. Methods and results:: We studied 45 patients with acute coronary syndrome (ACS), 50 patients with stable angina and angiographically verified CAD (SA) and 50 healthy controls. The distribution of NK cell subsets was determined by flow cytometry and NK cell-mediated cytotoxicity was quantified ex vivo. Both ACS and SA patients had significantly reduced numbers of CD56dim NK cells compared with controls. The patients also exhibited a significant decrease in NK cell activity. The loss in NK cell function was not related to inflammatory activity or metabolic status. Conclusion:: Both stable and unstable conditions of CAD were associated with a redistribution of circulating lymphocytes, comprising a significant reduction of CD56dim NK cells and a concomitant loss of NK cell function. The findings suggest the presence of a persistent immune aberration in CAD patients independent of their clinical setting or systemic inflammatory state. © 2005 Elsevier Ireland Ltd. All rights reserved.

  • 38.
    Jonasson, Lena
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Natural killer cells in coronary artery disease2004In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 4, p. 312-312Article in journal (Refereed)
  • 39.
    Kvarnström, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Mechanisms in inflammatory demyelinating diseases of the nervous system: immunological and methodological aspects2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The diseases studied in this thesis, Guillain-Barré Syndrome (GBS), Multiple Sclerosis (MS) and Polyneuropathy associated with monoclonal gammopathy of uncertain significance (PNMGUS), are of autoimmune origin with myelin components as putative auto antigens. T cells are important for the pathogenesis, as well as the cytokine network and autoantibodies. For all of these diseases, the immunopathogenisis is not fully understood and even if there are treatments available, none of them are curative and there are side effects. Thus there is a need for further clues in the immune mechanisms. Contrary to PNMGUS and MS, GBS is generally self-limiting. The mechanisms of the beneficial effect of interferon-beta (IFN-ß) treatment in MS are not fully understood, (although alterations in the cytokine levels are subject to many reports). In PNMGUS, the proliferation of a monoclonal B cell clone and its antibody production are of great significance, however additional immune mechanisms are also of interest like the role of T cells and the role of B cells as antigen presenting cells.

    In studies of cytokines, frozen cells are often used, sometimes for practical reasons, so also in this thesis. Therefore effects of cryopreservation on cellular expression/secretion of cytokines were studied. The expression before compared to after cryopreservation of IFN-γ, IL-4, IL-5, IL-9, IL-10 and IL-13 was analysed with ELISA, ELISPOT and/or real time RT-PCR We found that the process of cryopreservation and thawing does affect the expression of cytokines, both at the protein and the mRNA level. The most consistent fmding was that expression of IL-4 was generally decreased in spontaneous and auto-antigen/allergen induced expression in cryopreserved cells. Thus, this study points out the importance of investigation of the effects of freezing for each cytokine, stimuli and patient group before using frozen cells in studies of in vitro cytokine secretion.

    The secretion of IL-4, IFN-γ, TGF-ß, IL-6, and TNF-α during the course of GBS was analysed with ELISPOT and cell-ELISA. Our findings indicate a down-regulatory role for TGF-ß and IL-4 in GBS.

    The longitudinal effects over one year of IFN-ß treatment on secretion of IL-4, IFN-γ and IL-10 was analysed with the ELISPOT technique and IL-13 and IL-17 was analysed in cell supernatants with ELISA. A general finding was that surprisingly few changes occurred, and that most changes occurred early (6 weeks - 3 months). However, we found a shift in the cytokine balance towards more IL-4 and IL-10 secretion and/or less IFN-γ secretion during the treatment as the ratios of IL-4/IFN-γ as well as of IL-10/IFN-γ were increased. The interesting pro-inflammatory cytokine IL-17, associated with T cell mediated autoimmunity, has not been previously investigated during IFN-ß treatment in MS and our findings of decreased IL-17 levels after one year of treatment could be a beneficial result of the IFN-ß treatment.

    B cell clones from a patient with PNMGUS were successfully established by isolating B cells with myelin protein zero (P0) coated magnetic beads and subsequently transforming with Epstein-Barr virus (EBV). The clones were characterised and for instance they strongly expressed HLA-DR and CD80, compatible with antigen-presenting properties. The cell lines may provide useful tools in studies of PNMGUS.

    List of papers
    1. Effect of cryopreservation on expression of Th1 and Th2 cytokines in blood mononuclear cells from patients with different cytokine profiles, analysed with three common assays: an overall decrease of interleukin-4: An overall decrease of interleukin-4
    Open this publication in new window or tab >>Effect of cryopreservation on expression of Th1 and Th2 cytokines in blood mononuclear cells from patients with different cytokine profiles, analysed with three common assays: an overall decrease of interleukin-4: An overall decrease of interleukin-4
    2004 (English)In: Cryobiology, ISSN 0011-2240, E-ISSN 1090-2392, Vol. 49, no 2, p. 157-168Article in journal (Refereed) Published
    Abstract [en]

    Studies on cytokine expression in blood cells are commonly performed on cryopreserved cells. Previous studies show that cryopreservation affects cytokine expression, but the findings are not consistent. This may be due to divergent effects of freezing on different cytokines, different stimuli, and different patient groups or to the use of different assays in the studies. This study was designed to investigate the effect of freezing on spontaneous, auto-antigen, allergen, and mitogen induced cytokine secretion from peripheral blood mononuclear cells from several groups of patients expressing different cytokine profiles; multiple sclerosis, atopic children, non-atopic children, and pregnant women. The expression of IFN-γ, IL-4, IL-5, IL-9, IL-10, and IL-13 was analysed with ELISA, ELISPOT and/or real time RT-PCR. Our data provide evidence that the process of cryopreservation and thawing does affect the expression of cytokines, both at the protein and the mRNA level. Moreover, the effect varied among different cytokines, different stimuli, and different patient groups, which partly may be explained by differences in optimal freezing conditions for non-activated and activated cells. An increase of allergen and PHA stimulated IFN-γ secretion in atopic children was found following cryopreservation, but no such increase in auto-antigen induced IFN-γ was seen in MS-patients. The most consistent finding was that expression of IL-4 was generally decreased in spontaneous and auto-antigen/allergen induced expression in cryopreserved cells. In conclusion, this study points out the importance of investigation of the effects of freezing for each cytokine, stimuli and patient group before using frozen cells in studies of in vitro cytokine secretion.

    Keywords
    Cryopreservation, cytokine, IL-4, ELISA, ELISPOT, Real time RT-PCR
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-22345 (URN)10.1016/j.cryobiol.2004.06.003 (DOI)1546 (Local ID)1546 (Archive number)1546 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    2. Elevated number of cells secreting transforming growth factor β in Guillain-Barré syndrome
    Open this publication in new window or tab >>Elevated number of cells secreting transforming growth factor β in Guillain-Barré syndrome
    Show others...
    2003 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 111, no 12, p. 1095-1104Article in journal (Refereed) Published
    Abstract [en]

    We used ELISPOT and cell ELISA to study secretion of IL-4, IFN-γ, TGF-β, IL-6, and TNF-α by circulating mononuclear cells during the course of Guillain-Barré syndrome (GBS). Compared to healthy controls, patients with GBS had higher numbers of TGF-β-secreting cells and the number of individuals with myelin-peptide-induced IL-4 and TGF-β secretion was higher in the GBS group. No significant differences were seen concerning the predominantly pro-inflammatory cytokines IFN-γ, IL-6 or TNF-α. Our findings indicate a down-regulatory role for TGF-β and IL-4 in GBS.

    Keywords
    Cytokines, ELISPOT, Guillain-Barré, IL-4, Syndrome, TGF-ß
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-46369 (URN)10.1111/j.1600-0463.2003.apm1111204.x (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13Bibliographically approved
    3. IFN-ß treatment in multiple sclerosis: Longitudinal effects on secretion of IFN-γ, IL-4, IL-10, IL-13 and IL-17
    Open this publication in new window or tab >>IFN-ß treatment in multiple sclerosis: Longitudinal effects on secretion of IFN-γ, IL-4, IL-10, IL-13 and IL-17
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Proinflammatory cytokines like IFN-γ and TNF-α seem to have disease-promoting roles in multiple sclerosis (MS) whereas anti-inflammatory cytokines like IL-10 and TGF-ß may downregulate the disease. IFN-ß treatment reduces the frequency and severity of relapses, however, the mechanisms of action for IFN-ß are only partly understood and modulation of cytokine secretion could be one possible explanation for the therapeutic effects. The IFN-ß products approved for the treatment of MS differ in their composition and effects, and recently differences in effects on cytokine secretion were reported. Peripheral blood was collected from 25 patients with MS, both IFN-ß1a and IFN-ß1b treated, before onset of treatment and after 6 weeks, 3 months, 6 months and one year. Spontaneous as well as myelin specific secretion of IL-4, IFN-γ and IL-10 was analysed with the ELISPOT technique. PHA stimulated secretion of IL-13 and IL-17 was analysed in cell supernatants with ELISA. A general finding was that surprisingly few changes occurred, and that most changes occurred early (6 weeks - 3 months). We found a shift in the cytokine balance towards more IL-4 and IL-10 secretion and/or less IFN-γ secretion during the treatment as the ratios of IL-4!IFN-y as well as of IL-10/IFN-γ were increased. The interesting pro-inflammatory cytokine IL-17, that has been associated with T-cell mediated autoimmunity, has not been previously investigated during IFN-ß treatment in MS. Our findings of decreased IL-17 levels after one year of treatment, following an increase in early treatment, could be a beneficial result of the IFN-ß treatment. Further we noticed differences in effects on cytokines of IFN-ß1a and IFN-ß1b respectively; the latter seemed to have more effects on cytokine secretion.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84278 (URN)
    Available from: 2012-10-03 Created: 2012-10-03 Last updated: 2013-08-29Bibliographically approved
    4. Myelin protein P0-specific IgM producing monoclonal B cell lines were established from polyneuropathy patients with monoclonal gammopathy of undetermined significance (MGUS)
    Open this publication in new window or tab >>Myelin protein P0-specific IgM producing monoclonal B cell lines were established from polyneuropathy patients with monoclonal gammopathy of undetermined significance (MGUS)
    Show others...
    2002 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 127, no 2, p. 255-262Article in journal (Refereed) Published
    Abstract [en]

    Monoclonal expansion of B cells and plasma cells, producing antibodies against ‘self’ molecules, can be found not only in different autoimmune diseases, such as peripheral neuropathy (PN), but also in malignancies, such as Waldenström’s macroglobulinaemia and B-type of chronic lymphocytic leukaemia (B-CLL), as well as in precancerous conditions including monoclonal gammopathy of undetermined significance (MGUS). About 50% of patients with PN-MGUS have serum antibodies against peripheral nerve myelin, but the specific role of these antibodies remains uncertain. The aims of the study were to establish, and characterize, myelin-specific B cell clones from peripheral blood of patients with PN-MGUS, by selection of cells bearing specific membrane Ig-receptors for myelin protein P0, using beads coated with P0. P0-coated magnetic beads were used for selection of cells, which subsequently were transformed by Epstein–Barr virus. The specificity of secreted antibodies was tested by ELISA. Two of the clones producing anti-P0 antibodies were selected and expanded. The magnetic selection procedure was repeated and new clones established. The cells were CD5+ positive, although the expression declined in vitro over time. The anti-P0 antibodies were of IgM-λ type. The antibodies belonged to the VH3 gene family with presence of somatic mutations. The IgM reacted with P0 and myelin-associated glycoprotein (MAG), and showed no evidence for polyreactivity, in contrast to other IgM CD5+ clones included in the study as controls. The expanded clones expressed CD80 and HLA-DR, which is compatible with properties of antigen-presenting cells. The immunomagnetic selection technique was successfully used for isolation of antimyelin protein P0-specific clones. The cell lines may provide useful tools in studies of monoclonal gammopathies, leukaemia, and autoimmune diseases, including aspects of antigen-presentation by these cells followed by T cell activation.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25117 (URN)10.1046/j.1365-2249.2002.01739.x (DOI)9550 (Local ID)9550 (Archive number)9550 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
  • 40.
    Kvarnström, Maria
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Vrethem, Magnus
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Department of Neuroscience and Locomotion, Neurophysiology. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    IFN-ß treatment in multiple sclerosis: Longitudinal effects on secretion of IFN-γ, IL-4, IL-10, IL-13 and IL-17Manuscript (preprint) (Other academic)
    Abstract [en]

    Proinflammatory cytokines like IFN-γ and TNF-α seem to have disease-promoting roles in multiple sclerosis (MS) whereas anti-inflammatory cytokines like IL-10 and TGF-ß may downregulate the disease. IFN-ß treatment reduces the frequency and severity of relapses, however, the mechanisms of action for IFN-ß are only partly understood and modulation of cytokine secretion could be one possible explanation for the therapeutic effects. The IFN-ß products approved for the treatment of MS differ in their composition and effects, and recently differences in effects on cytokine secretion were reported. Peripheral blood was collected from 25 patients with MS, both IFN-ß1a and IFN-ß1b treated, before onset of treatment and after 6 weeks, 3 months, 6 months and one year. Spontaneous as well as myelin specific secretion of IL-4, IFN-γ and IL-10 was analysed with the ELISPOT technique. PHA stimulated secretion of IL-13 and IL-17 was analysed in cell supernatants with ELISA. A general finding was that surprisingly few changes occurred, and that most changes occurred early (6 weeks - 3 months). We found a shift in the cytokine balance towards more IL-4 and IL-10 secretion and/or less IFN-γ secretion during the treatment as the ratios of IL-4!IFN-y as well as of IL-10/IFN-γ were increased. The interesting pro-inflammatory cytokine IL-17, that has been associated with T-cell mediated autoimmunity, has not been previously investigated during IFN-ß treatment in MS. Our findings of decreased IL-17 levels after one year of treatment, following an increase in early treatment, could be a beneficial result of the IFN-ß treatment. Further we noticed differences in effects on cytokines of IFN-ß1a and IFN-ß1b respectively; the latter seemed to have more effects on cytokine secretion.

  • 41.
    Kvarnström, Maria
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Effect of cryopreservation on expression of Th1 and Th2 cytokines in blood mononuclear cells from patients with different cytokine profiles, analysed with three common assays: an overall decrease of interleukin-4: An overall decrease of interleukin-42004In: Cryobiology, ISSN 0011-2240, E-ISSN 1090-2392, Vol. 49, no 2, p. 157-168Article in journal (Refereed)
    Abstract [en]

    Studies on cytokine expression in blood cells are commonly performed on cryopreserved cells. Previous studies show that cryopreservation affects cytokine expression, but the findings are not consistent. This may be due to divergent effects of freezing on different cytokines, different stimuli, and different patient groups or to the use of different assays in the studies. This study was designed to investigate the effect of freezing on spontaneous, auto-antigen, allergen, and mitogen induced cytokine secretion from peripheral blood mononuclear cells from several groups of patients expressing different cytokine profiles; multiple sclerosis, atopic children, non-atopic children, and pregnant women. The expression of IFN-γ, IL-4, IL-5, IL-9, IL-10, and IL-13 was analysed with ELISA, ELISPOT and/or real time RT-PCR. Our data provide evidence that the process of cryopreservation and thawing does affect the expression of cytokines, both at the protein and the mRNA level. Moreover, the effect varied among different cytokines, different stimuli, and different patient groups, which partly may be explained by differences in optimal freezing conditions for non-activated and activated cells. An increase of allergen and PHA stimulated IFN-γ secretion in atopic children was found following cryopreservation, but no such increase in auto-antigen induced IFN-γ was seen in MS-patients. The most consistent finding was that expression of IL-4 was generally decreased in spontaneous and auto-antigen/allergen induced expression in cryopreserved cells. In conclusion, this study points out the importance of investigation of the effects of freezing for each cytokine, stimuli and patient group before using frozen cells in studies of in vitro cytokine secretion.

  • 42.
    Kvarnström, Maria
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Sidorova, E.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Nilsson, Joakim
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Vrethem, Magnus
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Söderberg, O.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Johansson, Malin
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Rosén, Anders
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Myelin protein P0-specific IgM producing monoclonal B cell lines were established from polyneuropathy patients with monoclonal gammopathy of undetermined significance (MGUS)2002In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 127, no 2, p. 255-262Article in journal (Refereed)
    Abstract [en]

    Monoclonal expansion of B cells and plasma cells, producing antibodies against ‘self’ molecules, can be found not only in different autoimmune diseases, such as peripheral neuropathy (PN), but also in malignancies, such as Waldenström’s macroglobulinaemia and B-type of chronic lymphocytic leukaemia (B-CLL), as well as in precancerous conditions including monoclonal gammopathy of undetermined significance (MGUS). About 50% of patients with PN-MGUS have serum antibodies against peripheral nerve myelin, but the specific role of these antibodies remains uncertain. The aims of the study were to establish, and characterize, myelin-specific B cell clones from peripheral blood of patients with PN-MGUS, by selection of cells bearing specific membrane Ig-receptors for myelin protein P0, using beads coated with P0. P0-coated magnetic beads were used for selection of cells, which subsequently were transformed by Epstein–Barr virus. The specificity of secreted antibodies was tested by ELISA. Two of the clones producing anti-P0 antibodies were selected and expanded. The magnetic selection procedure was repeated and new clones established. The cells were CD5+ positive, although the expression declined in vitro over time. The anti-P0 antibodies were of IgM-λ type. The antibodies belonged to the VH3 gene family with presence of somatic mutations. The IgM reacted with P0 and myelin-associated glycoprotein (MAG), and showed no evidence for polyreactivity, in contrast to other IgM CD5+ clones included in the study as controls. The expanded clones expressed CD80 and HLA-DR, which is compatible with properties of antigen-presenting cells. The immunomagnetic selection technique was successfully used for isolation of antimyelin protein P0-specific clones. The cell lines may provide useful tools in studies of monoclonal gammopathies, leukaemia, and autoimmune diseases, including aspects of antigen-presentation by these cells followed by T cell activation.

  • 43.
    Lidebjer, Caroline
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Leanderson, Per
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Ernerudh, Jan
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Jonasson, Lena
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Low plasma levels of oxygenated carotenoids in patients with coronary artery disease2007In: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 17, no 6, p. 448-456Article in journal (Refereed)
    Abstract [en]

    Background and aims: Low circulating levels of carotenoids have been associated with cardiovascular disease. The distribution of different carotenoids in blood may have an impact on the cardioprotective capacity. The aim of the present study was to determine the plasma levels of 6 major carotenoids in patients with coronary artery disease (CAD) and relate the findings to clinical, metabolic and immune parameters. Methods and results: Plasma levels of oxygenated carotenoids (lutein, zeaxanthin, β-cryptoxanthin) and hydrocarbon carotenoids (α-carotene, β-carotene, lycopene) were determined in 39 patients with acute coronary syndrome, 50 patients with stable CAD and 50 controls. Serological assays for inflammatory activity and flow cytometrical analysis of lymphocyte subsets were performed. Both patient groups had significantly lower plasma levels of oxygenated carotenoids, in particular lutein + zeaxanthin, compared to controls. Low levels of oxygenated carotenoids were associated with smoking, high body mass index (BMI), low high density lipoprotein (HDL) cholesterol and, to a minor degree, inflammatory activity. Plasma levels of lutein + zeaxanthin were independently associated with the proportions of natural killer (NK) cells, but not with other lymphocytes, in blood. Conclusion: Among carotenoids, lutein + zeaxanthin and β-cryptoxanthin were significantly reduced in CAD patients independent of clinical setting. The levels were correlated to a number of established cardiovascular risk factors. In addition, the relationship between NK cells and lutein + zeaxanthin may indicate a particular role for certain carotenoids in the immunological scenario of CAD. © 2006 Elsevier B.V. All rights reserved.

  • 44.
    Lindvall, Björn
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Immunohistological studies on muscle biopsies: clinical and pathogenetic aspects on inflammatory myopathies2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Inflammatory myopathies constitute a heterogeneous group of disorders comprising polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM), as well as overlap syndromes where inflammatory myopathy is associated with different inflammatory systemic diseases, e.g, Sjögren's syndrome. Immunohistochemical methods are increasingly used in the diagnostic evaluation of muscle biopsies, as well as in the search for pathogenetic mechanisms in neuromuscular diseases. The aim of the present thesis was to evaluate immunological markers in the context of diagnostic use and pathogenetic mechanisms in patients with inflammatory myopathies (IM).

    In the first paper, the expression of inflammatory markers was investigated in muscle biopsies from 58 healthy subjects, since no large studies on normal expression have been reported previously. MHC class I stained capillaries but not muscle fibres. No capillary or muscle fibre staining was found of MHC class II, complement activation marker MAC, or the regeneration marker neonatal myosin heavy chain, whereas the adhesion molecule ICAM-I was constitutively expressed on capillary endothelial cells. The expression was similar in morphologically completely normal muscle biopsies obtained from clinical routine, justifying the use of such biopsies as normal reference, although some caution is warranted because of individuals with higher expression of inflammatory markers.

    Adhesion molecules regulate cell to cell interactions, e.g. they are involved in recruiting cells into inflammatory lesions in muscles. In a group of consecutive patients (n=22) with inflammatory infiltrates pairs of adhesion molecules were examined on infiltrating cells and vascular endothelial cells. VLA-4, known to be important in chronic inflammation, was found to be expressed mostly on infiltrating cells in definite PM, whereas LFA-1 was expressed in all types of IM. These findings suggest a diagnostic potential of the LFA-1/VLA-4 ratio, and a role for VLA-4/VCAM-1 in the pathogenesis of PM.

    In a large study of patients (n=48) with primary Sjögren's syndrome (pSS), we described muscle histology and immunohistochemical findings in relation to muscle pain (n=36), a common complaint of patients with pSS. Morphological changes, as perivascular inflammation was common in pSS. A surprisingly high proportion of patients displayed IBM-Iike changes, such as rimmed vacuoles, inflammation and atrophic fibres. Immunohistochemically, MHC class I and MAC showed increased expression, but no single finding showed any relation to muscle pain. MAC expression indicates a role for complement activation in pSS associated myositis.

    The finding of IBM-Iike changes in pSS, resulted in a subsequent comparative study of cytoplasmic and vacuolar proteins in classical IBM and pSS. Although more frequently found in IBM, the same vacuolar proteins were found in muscle biopsies from patients with pSS. Clinical symptoms differed between IBM and pSS associated myositis, indicating that these diseases represent different entities. The similarity in histological findings suggests that non-specific mechanisms may operate and lead to the same end result. We therefore propose that vacuolar myositis in pSS should be regarded as a separate entity, different from classical IBM and suggest the term aIBM (autoimmune associated) for patients with IBM-Iike changes and associated autoimmune disease.

    List of papers
    1. Immunohistochemical markers MHC class I, MHC class II, ICAM-1, MAC and neonatal myosin heavy chain in muscle biopsies: Expression in healthy subjects, normal muscle biopsies and inflammatory myopathies
    Open this publication in new window or tab >>Immunohistochemical markers MHC class I, MHC class II, ICAM-1, MAC and neonatal myosin heavy chain in muscle biopsies: Expression in healthy subjects, normal muscle biopsies and inflammatory myopathies
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Although immunohistochemistry on muscle biopsies is widely used scientifically and clinically, information is limited regarding the expression in normal healthy subjects. In the present study we investigated the expression of relevant immune markers in a large material (n=58) of healthy subjects and compared with the expression in morphologically normal muscle biopsies (n=46) obtained from clinical routine. As a reference of inflammation, muscle biopsies from idiopathic inflammatmy myopathies (IIM) were used (n=22).

    We found that the expression in healthy subjects was not significantly different from that in morphologically normal biopsies, although a few individuals with minimal morphological aberrations also showed higher expression of immune markers. The IIM group showed significantly higher expression of all markers. In brief, major histocompatibility complex (MHC) class I was nmmally not, or very weakly, expressed on muscle fibres, MHC class II was not expressed on capillary endothelial cells, whereas intercellular adhesion molecule (ICAM)-1 was constitutively expressed to a ce1tain degree on capillmy endothelial cells. The complement activation marker membrane attack complex (MAC) was merely absent in nonnal biopsies. Neonatal myosin heavy chain was normally present only in a very few regenerating fibres. A constructed grading scale was found useful, based on normal occun·ence as well as intensity and distribution of expression.

    In conclusion we demonstrate the nmmal expression of MHC class I, MHC class II, ICAM-1, MAC and neonatal myosin as found in healthy subjects. The expression was similar in morphologically completely normal muscle biopsies obtained from clinical routine, justifyhtg the use of such biopsies as normal reference. Some caution is warranted for using biopsies with minimal morphological changes, since these showed increased expression of some inflammatory markers.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-81622 (URN)
    Available from: 2012-09-19 Created: 2012-09-19 Last updated: 2012-09-19Bibliographically approved
    2. The expression of adhesion molecules in muscle biopsies: the LFA-1/VLA-4 ratio in polymyositis
    Open this publication in new window or tab >>The expression of adhesion molecules in muscle biopsies: the LFA-1/VLA-4 ratio in polymyositis
    Show others...
    2003 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 107, no 2, p. 134-141Article in journal (Refereed) Published
    Abstract [en]

    Objectives– The expression of three pairs of adhesion receptors and ligands was examined in 22 consecutive muscle biopsies showing morphological signs of inflammation.

    Material and methods– The following groups were studied: patients with polymyositis (PM) (n=7), patients with myositis that did not fulfil criteria for PM, i.e. suspected PM (n=5), patients with other diseases, with no clinical signs of inflammatory myopathy (n=6), and a small group of non-PM inflammatory myopathies (n=4). The endothelial expression of ICAM-1, VCAM-1 and E-selectin was evaluated, as was the cellular expression of LFA-1, VLA-4 and SLex. In addition, the expression of MHC class I and II was studied.

    Results– The ratio between the number of cells expressing LFA-1 and VLA-4 showed significant differences between the groups, with the lowest values in PM.

    Conclusion– The LFA-1/VLA-4 ratio should be suitable for diagnostic purposes. Our findings also indicate that the VLA-4/VCAM-1 system is important for chronic T cell inflammation in muscle, in line with findings in other “hidden” organs like joints and the central nervous system.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26433 (URN)10.1034/j.1600-0404.2003.02062.x (DOI)10976 (Local ID)10976 (Archive number)10976 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    3. Subclinical myositis is common in primary Sjögren's syndrome and is not related to muscle pain
    Open this publication in new window or tab >>Subclinical myositis is common in primary Sjögren's syndrome and is not related to muscle pain
    2002 (English)In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 29, no 4, p. 717-725Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE: Although muscle pain is common in primary Sjögren's syndrome (SS), the underlying mechanisms are mainly unknown. We studied all patients with SS at our rheumatology unit with respect to muscle pain in general and to fibromyalgia (FM), and correlated clinical data to muscle biopsy findings.

    METHODS: We investigated 48 patients with SS according to the modified European diagnostic criteria. The ACR criteria for FM were used to subgroup the patients. Muscle biopsy was performed in 36 patients. Light microscope morphology and immunohistochemical expression of MHC class I, MHC class II, and membrane attack complex (MAC) were studied.

    RESULTS: We found 44% of patients complained of muscle pain; 27% fulfilled the ACR criteria for FM, whereas 17% had other forms of myalgia. Muscle pain could not be related to histopathological findings. Signs of inflammation were found in 26 of 36 biopsies (72%), and inflammation combined with degeneration/regeneration (i.e., histological signs of polymyositis) in 17 biopsies (47%). However, only 5 patients (14%) had clinical as well as histological signs of polymyositis. Eight muscle biopsies (22%) showed histological features of inclusion body myositis (IBM). However, no patient had clinical symptoms suggestive of this disease. Abnormal expression of MHC class I, MHC class II, and MAC was found in 18 (50%), 16 (44%), and 27 (75%) patients, respectively.

    CONCLUSION: Muscle pain, especially FM, is common in SS. Histopathological signs of myositis are very common in SS. However, muscle symptoms are not related to histological signs of muscle inflammation. IBM-like findings may represent vacuolar myopathic degeneration due to previous subclinical muscle inflammation rather than a specific clinical entity.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26377 (URN)10911 (Local ID)10911 (Archive number)10911 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    4. Inclusion body myopathy in Primary Sjögren's syndrome: clinical and histopathological features in relation to sporadic inclusion body myositis
    Open this publication in new window or tab >>Inclusion body myopathy in Primary Sjögren's syndrome: clinical and histopathological features in relation to sporadic inclusion body myositis
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Inclusion body myositis (IBM) is a chronic, acquired inflammatory myopathy with typical clinical symptoms and characteristic histopathological features in muscle biopsy. However, there are still uncertainties in diagnostic criteria, implying that disorders of potentially different origin may be classified as IBM. In particular, muscle biopsy findings of vacuolar myopathy in Sjögren's syndrome have indicated an association with IBM, and so far vacuolar Sjögren myopathy is included in the IBM entity.

    We therefore compared clinical and histopathological features in a group of patients with sporadic-IBM (s-IBM, n=11) with a group of patients with primary Sjögren's syndrome (pSS) with IBM-like findings in their muscle biopsies (n=10). Biopsies from s-IBM but not from Sjögren patients stained for Congo-red, whereas no other obvious differences were fonnd concerning morphological or biochemical fmdings of vacuolar content (hyperphosphorylated tau-protein: SMI 31 and SMI 310, ubiquitin, tau-protein, ß-amyloid, ß-amyloid precursor protein). Striking differences were fonnd in the clinical picture, age of onset and gender preponderance (females in pSS and males in s-IBM).

    Based on the different clinical features and the difference in Congo-red staining, we suggest that vacuolar myopathy in pSS should be regarded as a separate entity, not to be included in the classical s-IBM group. IBM-like fmdings in muscle biopsy are observed in different types of systemic inflammatory diseases, and could preferably be designated as autoimmune associated IBM (a-IBM).

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-81623 (URN)
    Available from: 2012-09-19 Created: 2012-09-19 Last updated: 2013-10-25Bibliographically approved
  • 45.
    Lindvall, Björn
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Bengtsson, Ann
    Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Eriksson, Per
    Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Subclinical myositis is common in primary Sjögren's syndrome and is not related to muscle pain2002In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 29, no 4, p. 717-725Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Although muscle pain is common in primary Sjögren's syndrome (SS), the underlying mechanisms are mainly unknown. We studied all patients with SS at our rheumatology unit with respect to muscle pain in general and to fibromyalgia (FM), and correlated clinical data to muscle biopsy findings.

    METHODS: We investigated 48 patients with SS according to the modified European diagnostic criteria. The ACR criteria for FM were used to subgroup the patients. Muscle biopsy was performed in 36 patients. Light microscope morphology and immunohistochemical expression of MHC class I, MHC class II, and membrane attack complex (MAC) were studied.

    RESULTS: We found 44% of patients complained of muscle pain; 27% fulfilled the ACR criteria for FM, whereas 17% had other forms of myalgia. Muscle pain could not be related to histopathological findings. Signs of inflammation were found in 26 of 36 biopsies (72%), and inflammation combined with degeneration/regeneration (i.e., histological signs of polymyositis) in 17 biopsies (47%). However, only 5 patients (14%) had clinical as well as histological signs of polymyositis. Eight muscle biopsies (22%) showed histological features of inclusion body myositis (IBM). However, no patient had clinical symptoms suggestive of this disease. Abnormal expression of MHC class I, MHC class II, and MAC was found in 18 (50%), 16 (44%), and 27 (75%) patients, respectively.

    CONCLUSION: Muscle pain, especially FM, is common in SS. Histopathological signs of myositis are very common in SS. However, muscle symptoms are not related to histological signs of muscle inflammation. IBM-like findings may represent vacuolar myopathic degeneration due to previous subclinical muscle inflammation rather than a specific clinical entity.

  • 46.
    Lindvall, Björn
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Eriksson, Per
    Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Inclusion body myopathy in Primary Sjögren's syndrome: clinical and histopathological features in relation to sporadic inclusion body myositisManuscript (preprint) (Other academic)
    Abstract [en]

    Inclusion body myositis (IBM) is a chronic, acquired inflammatory myopathy with typical clinical symptoms and characteristic histopathological features in muscle biopsy. However, there are still uncertainties in diagnostic criteria, implying that disorders of potentially different origin may be classified as IBM. In particular, muscle biopsy findings of vacuolar myopathy in Sjögren's syndrome have indicated an association with IBM, and so far vacuolar Sjögren myopathy is included in the IBM entity.

    We therefore compared clinical and histopathological features in a group of patients with sporadic-IBM (s-IBM, n=11) with a group of patients with primary Sjögren's syndrome (pSS) with IBM-like findings in their muscle biopsies (n=10). Biopsies from s-IBM but not from Sjögren patients stained for Congo-red, whereas no other obvious differences were fonnd concerning morphological or biochemical fmdings of vacuolar content (hyperphosphorylated tau-protein: SMI 31 and SMI 310, ubiquitin, tau-protein, ß-amyloid, ß-amyloid precursor protein). Striking differences were fonnd in the clinical picture, age of onset and gender preponderance (females in pSS and males in s-IBM).

    Based on the different clinical features and the difference in Congo-red staining, we suggest that vacuolar myopathy in pSS should be regarded as a separate entity, not to be included in the classical s-IBM group. IBM-like fmdings in muscle biopsy are observed in different types of systemic inflammatory diseases, and could preferably be designated as autoimmune associated IBM (a-IBM).

  • 47.
    Lindvall, Björn
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Immunohistochemical markers MHC class I, MHC class II, ICAM-1, MAC and neonatal myosin heavy chain in muscle biopsies: Expression in healthy subjects, normal muscle biopsies and inflammatory myopathiesManuscript (preprint) (Other academic)
    Abstract [en]

    Although immunohistochemistry on muscle biopsies is widely used scientifically and clinically, information is limited regarding the expression in normal healthy subjects. In the present study we investigated the expression of relevant immune markers in a large material (n=58) of healthy subjects and compared with the expression in morphologically normal muscle biopsies (n=46) obtained from clinical routine. As a reference of inflammation, muscle biopsies from idiopathic inflammatmy myopathies (IIM) were used (n=22).

    We found that the expression in healthy subjects was not significantly different from that in morphologically normal biopsies, although a few individuals with minimal morphological aberrations also showed higher expression of immune markers. The IIM group showed significantly higher expression of all markers. In brief, major histocompatibility complex (MHC) class I was nmmally not, or very weakly, expressed on muscle fibres, MHC class II was not expressed on capillary endothelial cells, whereas intercellular adhesion molecule (ICAM)-1 was constitutively expressed to a ce1tain degree on capillmy endothelial cells. The complement activation marker membrane attack complex (MAC) was merely absent in nonnal biopsies. Neonatal myosin heavy chain was normally present only in a very few regenerating fibres. A constructed grading scale was found useful, based on normal occun·ence as well as intensity and distribution of expression.

    In conclusion we demonstrate the nmmal expression of MHC class I, MHC class II, ICAM-1, MAC and neonatal myosin as found in healthy subjects. The expression was similar in morphologically completely normal muscle biopsies obtained from clinical routine, justifyhtg the use of such biopsies as normal reference. Some caution is warranted for using biopsies with minimal morphological changes, since these showed increased expression of some inflammatory markers.

  • 48.
    Ludvigsson, Johnny
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Samuelsson, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Johansson, C
    Stenhammar, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Berlin, Gösta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Transfusion Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Photopheresis at onset of type 1 diabetes: A randomised, double blind, placebo controlled trial2001In: Archives of Disease in Childhood, ISSN 0003-9888, E-ISSN 1468-2044, Vol. 85, no 2, p. 149-154Article in journal (Refereed)
    Abstract [en]

    Background - In recent years photopheresis, an extracorporeal form of photochemotherapy using psoralen and ultraviolet A irradiation of leucocytes, has been claimed to be an effective form of immunomodulation. Aim - To evaluate its effect in type 1 diabetes we performed a double blind, controlled study using placebo tablets and sham pheresis in the control group. Methods - A total of 49 children, aged 10-18 years of age at diagnosis of type 1 diabetes were included, 40 fulfilled the study and were followed for three years (19 received active treatment with photopheresis and 21 placebo treatment). Results - The actively treated children secreted significantly more C peptide in urine during follow up than control children. C peptide values in serum showed corresponding differences between the two groups. The insulin dose/kg body weight needed to achieve satisfactory HbA1c values was always lower in the photopheresis group, there was no difference between the groups regarding HbAlc values during follow up. The treatment was well accepted except for nausea (n = 3) and urticaria (n = 1) in the actively treated group. There were no differences regarding weight or height, or episodes of infection between the two groups during follow up. Conclusion - Photopheresis does have an effect in addition to its possible placebo effect, shown as a weak but significant effect on the disease process at the onset of type 1 diabetes, an effect still noted after three years of follow up.