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  • 101.
    Skogh, Thomas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Letter: Comment on: Clinical utility of ANA measured by ELISA compared with ANA measured by immunofluorescence2010In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 49, no 2, p. 396-397Article in journal (Other academic)
    Abstract [en]

    n/a

  • 102.
    Skogman, Barbro H
    et al.
    Falun General Hospital.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Seroprevalence of Borrelia IgG antibodies among young Swedish children in relation to reported tick bites, symptoms and previous treatment for Lyme borreliosis: a population-based survey2010In: ARCHIVES OF DISEASE IN CHILDHOOD, ISSN 0003-9888, Vol. 95, no 12, p. 1013-1016Article in journal (Refereed)
    Abstract [en]

    Background Lyme borreliosis (LB) is the most common tickborne infection in Sweden and the seroprevalence of Borrelia immunoglobulin G (IgG) antibodies varies between 2% and 26%. The seroprevalence in young Swedish children is unknown and the relation to clinical data has not been previously studied. Objective To determine the seroprevalence of Borrelia IgG antibodies in serum of young Swedish children and to relate it to gender, geographical location, reported tick bites, symptoms and previous treatment for LB. Methods 2000 healthy 5-year-old children (n=2000) were randomly selected from among participants of a larger prospective population-based study, the ABIS (All Babies in Southeast Sweden) study. Serum samples were collected and a Borrelia specific ELISA test (Dako) were performed for IgG antibody detection. Clinical data were collected from questionnaires completed by the parents. Results The seroprevalence of Borrelia IgG antibodies was 3.2% (64/2000). Previous tick bite had been noted in 66% of these seropositive children but the majority (94%) had not previously been treated for LB. In addition, another 55 children reported a history of LB but were negative to Borrelia IgG antibodies in serum. Many of these seronegative children had received treatment for erythema migrans (n=24), which is a clinical diagnosis. Whether children were correctly treated or overtreated for LB is however unknown. No differences in gender, geographical location or reported tick bites were found when comparing Borrelia-seropositive children (n=64) and seronegative children with previous LB (n=55). Conclusion This population-based study demonstrates a Borrelia IgG antibody seroprevalence of 3.2% in young Swedish children. Very few of these seropositive children report previous symptoms or treatment for LB. Thus the findings suggest that exposure to the Borrelia spirochaete (with subsequent antibody response in serum) does occur in young children, mostly without giving rise to clinical LB. Future studies on cell-mediated immune responses are needed to investigate explanatory immunological mechanisms.

  • 103.
    Skogman, Barbro H
    et al.
    Falun General Hospital.
    Hellberg, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Bergström, Sven
    Umeå University.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Adaptive and Innate Immune Responsiveness to Borrelia burgdorferi sensu lato in Exposed Asymptomatic Children and Children with Previous Clinical Lyme Borreliosis2012In: Clinical & Developmental Immunology, ISSN 1740-2522, E-ISSN 1740-2530, Vol. 2012, no 294587Article in journal (Refereed)
    Abstract [en]

    Why some individuals develop clinical manifestations in Lyme borreliosis (LB) while others remain asymptomatic is largely unknown. Therefore, we wanted to investigate adaptive and innate immune responsiveness to Borrelia burgdorferi sensu lato in exposed Borrelia-antibody-positive asymptomatic children (n = 20), children with previous clinical LB (n = 24), and controls (n = 20). Blood samples were analyzed for Borrelia-specific interferon (IFN)-gamma, interleukin (IL)-4, and IL-17 secretion by ELISPOT and Borrelia-induced IL-1 beta, IL-6, IL-10, IL-12(p70), and tumor necrosis factor (TNF) secretion by Luminex. We found no significant differences in cytokine secretion between groups, but a tendency towards an increased spontaneous secretion of IL-6 was found among children with previous clinical LB. In conclusion, the adaptive or innate immune responsiveness to Borrelia burgdorferi sensu lato was similar in Borrelia-exposed asymptomatic children and children with previous clinical LB. Thus, the immunological mechanisms of importance for eradicating the spirochete effectively without developing clinical manifestations of LB remain unknown.

  • 104.
    Stenberg, Reidun
    et al.
    Örebro University Hospital.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences, Engelska: Faculty of Health Sciences, Medical Programme. Östergötlands Läns Landsting, Centre for Laboratory Medicine.
    Lindberg, Eva
    Örebro University Hospital.
    Schollin, Jens
    Örebro University Hospital.
    Increased Prevalence of Anti-gliadin Antibodies and Anti-tissue Transglutaminase Antibodies in Children With Cerebral Palsy2009In: JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, ISSN 0277-2116, Vol. 49, no 4, p. 424-429Article in journal (Refereed)
    Abstract [en]

    Aim and Objective: The aim of the study was to investigate whether there is any association between cerebral palsy (CP) and celiac disease(CD) in children. Patients and Methods: Ninety children between 18 months and 18 years of age (median 9 years) with CP were included. Antibodies (IgA and IgG) against gliadin (AGA), endomysium (EMA), and tissue transglutaminase (tTG) were measured. Children with elevated levels of these antibodies were offered a small-bowel biopsy. Results: Thirty-nine children showed an elevated level of 1 or more of the tested antibodies (43%). None had raised EMA antibodies. Presence of tetraplegia or dyskinesia was associated with increased antibody levels (P=0.045), as was a more severe functional type of CP (P=0.008). Children with elevated antibodies had a lower body weight (P=0.049), height (P=0.041), and body mass index (BMI) (P=0.014). Small-bowel biopsies were performed in 27 out of 39 children; 1 had CD and 2 had intraepithelial lymphocytosis. Conclusions: A large number of children with CP had elevated AGA and/or anti-tTG. Because these elevations were associated with lower weight, height, and BMI, it seemed of interest to speculate on how these findings correlated to CP and CD. However, we found no correlation between CP and CD.

  • 105.
    Stenberg, Reidun
    et al.
    Örebro University Hospital, Sweden .
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Magnuson, Anders
    Örebro University Hospital, Sweden .
    Hellberg, Dan
    Clin Research Centre, Sweden .
    Tysk, Curt
    Örebro University Hospital, Sweden .
    Increased Prevalence of Antibodies Against Dietary Proteins in Children and Young Adults With Cerebral Palsy2013In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 56, no 2, p. 233-238Article in journal (Refereed)
    Abstract [en]

    Objectives: Undernourishment is common in children with cerebral palsy (CP), but the reasons are unknown. We previously reported elevated levels of immunoglobulin (Ig) A and IgG antibodies against gliadin (AGA) and tissue transglutaminase (tTG) in 99 children and young adults with CP without characteristic findings of gluten enteropathy in small bowel biopsies. Our aim was to perform a case-control study of IgG antibodies against other dietary antigens, AGA, anti-tTG, and IgE antibodies against wheat and gluten. less thanbrgreater than less thanbrgreater thanMethods: Sera from 99 cases with CP and 99 healthy, age-and sex-matched controls were analysed with fluorescence enzyme-linked immunosorbent assay for detection of IgG antibodies against beta-lactoglobulin, casein, egg white, IgG-and IgA-AGA, IgA-anti-tTG, and IgE antibodies against gluten and wheat. less thanbrgreater than less thanbrgreater thanResults: Compared with controls, the odds ratio in cases with CP for having elevated levels of IgG antibodies against beta-lactoglobulin was 17.0 (95% confidence interval [CI] 2.3-128), against casein 11.0 (95% CI 2.6-46.8), and against egg white 7.0 (95% CI 1.6-30.8). The IgE responses for wheat/gluten were generally low. The tetraplegic and dyskinetic CP subtypes had significantly higher frequencies of elevated levels for all of the tested antibodies except IgG against egg white, and IgA-anti-tTG. A significantly lower weight was seen in cases with CP with positive versus negative serology. less thanbrgreater than less thanbrgreater thanConclusions: Elevated levels of IgG against dietary antigens were more frequent in the CP group compared with controls, and particularly in the tetraplegic and dyskinetic CP subtypes with the most severe neurologic handicap and undernourishment. Hypothetically, malnourishment may cause increased intestinal permeability and thus immunization against dietary antigens.

  • 106.
    Stenberg, Reidun
    et al.
    Department of Paediatrics, Örebro University Hospital,.
    Kaukinen, Katri
    Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, University of Tampere.
    Bengtsson, Mats
    Department of Clinical Immunology, University Hospital, Uppsala University.
    Lindberg, Eva
    Department of Paediatrics, Örebro University Hospital,.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Early developing celiac disease in children with cerebral palsy2011In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 53, no 6, p. 674-678Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: We have reported on increased levels of antibodies against gliadin and/or transglutaminase 2 (TG2) in children with cerebral palsy (CP) but without having increased prevalence of celiac disease (CD). The aim of the present study was to evaluate whether these children have mucosal signs of early developing CD, human leukocyte antigen (HLA)-DQ2/DQ8, and antibodies against deamidated gliadin peptides (DGP).

    PATIENTS AND METHODS: Stored blood samples from 16 children with CP were analyzed regarding HLA-DQ2/DQ8 and anti-DGP antibodies. HLA-DQ2/DQ8 were analyzed by polymerase chain reaction sequence-specific oligonucleotide probes. Anti-DGP antibodies were analyzed with enzyme-linked immunosorbent assay. Small-bowel biopsies from 15 of these children were available for immunohistochemistry regarding IgA colocalized with TG2, densities of α/β+ and γ/δ+ intraepithelial lymphocytes.

    RESULTS: Mucosal immunoglobulin A (IgA) deposits colocalized with TG2 were found in the small-bowel biopsy from 1 patient with serum IgA-class anti-TG2 antibodies, HLA-DQ2, and gastrointestinal complaints. Another 2 children had slightly increased numbers of mucosal α/β+ and/or γ/δ+ intraepithelial lymphocytes. In total, 10 of 16 children were HLA-DQ2 and/or DQ8-positive. Anti-DGP antibodies were detected in sera from 4 of 16 children.

    CONCLUSIONS: In the present study, 1 child with CP had IgA colocalizing with TG2 in the small-bowel mucosa, suggesting CD at an early stage. Although the majority of children with CP and elevated levels of CD-related seromarkers are HLA-DQ2 and/or DQ8-positive, they have neither classical nor early developing CD.

  • 107.
    Strindhall, J.
    et al.
    Department of Natural Science and Biomedicine, School of Health Sciences, Jönköping University, Box 1026, 551 11 Jönköping, Sweden.
    Nilsson, B.-O.
    Department of Infectious Diseases, Ryhov Hospital, 551 85 Jönköping, Sweden.
    Lofgren, S.
    Löfgren, S., Department of Microbiology, Ryhov Hospital, Jönköping, Sweden.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Pawelec, G.
    University of Tubingen Medical School, Center for Medical Research, ZMF, Waldhörnlestr. 22, D-72072 Tubingen, Germany.
    Johansson, B.
    Institute of Gerontology, School of Health Sciences, Jönköping University, Box 1026, 551 11 Jönköping, Sweden, Department of Psychology, Göteborg University, Box 500, 405 30 Göteborg, Sweden.
    Wikby, A.
    Department of Natural Science and Biomedicine, School of Health Sciences, Jönköping University, Box 1026, 551 11 Jönköping, Sweden.
    No Immune Risk Profile among individuals who reach 100 years of age: Findings from the Swedish NONA immune longitudinal study2007In: Experimental Gerontology, ISSN 0531-5565, E-ISSN 1873-6815, Vol. 42, no 8, p. 753-761Article in journal (Refereed)
    Abstract [en]

    In the present NONA immune longitudinal study, we investigate the previously identified Immune Risk Profile (IRP), defined by an inverted CD4/CD8 ratio and associated with persistent cytomegalovirus infection and increased numbers of CD8+CD28- cells, relative 6-year survival and age in NONA individuals. These subjects have now reached age 92, 96, and for the first time in this study, 100 years at follow-up. A 55 year old middle-aged group was used for comparison. Immunological monitoring included the analysis of numbers of lymphocytes and neutrophils, the T-cell subsets CD3+CD4+, CD3+CD8+, CD8+CD28+, CD8+CD28-, and the CD4/CD8 ratio. Longitudinal data were analysed by multivariate analyses of variance (MANOVA) from four measurement occasions at 2-year inter-intervals. One-way ANOVA was used for cross-sectional comparisons at baseline and the 6-year follow-up. The results confirmed the importance of the IRP as a major predictor of mortality in this population of very old. Moreover, the results suggested that survival to the age of 100 years is associated with selection of individuals with an "inverted" IRP that was stable across time, i.e., maintenance of a high CD4/CD8 ratio and low numbers of CD8+CD28- cells. The results underlines the importance of a longitudinal study design in dissecting immune parameters predictive of survival and show for the first time that centenarian status is associated with avoidance of the IRP over at least the previous 6 years and probably throughout life. © 2007 Elsevier Inc. All rights reserved.

  • 108.
    Strindhall, Jan
    et al.
    Jönköping University, Sweden.
    Skog, Mårten
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Bengner, M
    Ryhov Hospital, Sweden.
    Lofgren, S
    Ryhov County Hospital, Sweden.
    Matussek, A
    Ryhov County Hospital, Sweden.
    Nilsson, B O.
    Ryhov Hospital, Sweden.
    Wikby, A
    Jönköping University, Sweden.
    The inverted CD4/CD8 ratio and associated parameters in 66-year-old individuals: the Swedish HEXA immune study2013In: Age (Omaha), ISSN 0161-9152, E-ISSN 1574-4647, Vol. 35, no 3, p. 985-991Article in journal (Refereed)
    Abstract [en]

    The Swedish OCTO and NONA immune longitudinal studies were able to identify and confirm an immune risk profile (IRP) predictive of an increased 2-year mortality in very old individuals, 86–94 years of age. The IRP, was associated with persistent cytomegalovirus infection and characterized by inverted CD4/CD8 ratio and related to expansion of terminally differentiated effector memory T cells (TEMRA phenotype). In the present HEXA immune longitudinal study, we have examined a younger group of elderly individuals (n = 424, 66 years of age) in a population-based sample in the community of Jönköping, Sweden, to examine the relevance of findings previously demonstrated in the very old. Immunological monitoring that was conducted included T cell subsets and CMV-IgG and CMV-IgM serology. The result showed a prevalence of 15 % of individuals with an inverted CD4/CD8 ratio, which was associated with seropositivity to cytomegalovirus and increases in the level of TEMRA cells. The proportion of individuals with an inverted CD4/CD8 ratio was significantly higher in men whereas the numbers of CD3+CD4+ cells were significantly higher in women. In conclusion, these findings are very similar to those previously found by us in the Swedish longitudinal studies, suggesting that an immune profile previously identified in the very old also exists in the present sample of hexagenerians. Therefore, it will be important to examine clinical parameters, including morbidity and mortality, to assess whether the immune profile also is a risk profile associated with higher mortality in this sample of hexagenerians.

  • 109.
    Svensson, J
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    CD14(+) decidual macrophages from early human pregnancy: expression of markers associated with alternatively activated macrophages and requirements for their polarization2009In: in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 81, issue 2, 2009, Vol. 81, no 2, p. 147-148Conference paper (Refereed)
    Abstract [en]

    n/a

  • 110.
    Svensson, J
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Mirrasekhian, E
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Freland, Sofia
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    M-CSF produced by trophoblasts induces CD163, a marker of immune regulatory decidual macrophages in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 94, issue 1, pp 92-922012In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Elsevier , 2012, Vol. 94, no 1, p. 92-92Conference paper (Refereed)
    Abstract [en]

    n/a

  • 111.
    Svensson, Judit
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Matussek, Andreas
    Department of Clinical Microbiology, County Hospital Ryhov, Jönköping.
    Geffers, Robert
    Mucosal Immunity, Helmholtz Centre for Infection Research (HCI), Braunschweig, Germany.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Gene expression and protein secretion patterns in decidual macrophages and different M1 and M2 macrophage populations with focus on M-CSF and IL-10 as polarising factors in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 151-1512011In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Elsevier , 2011, Vol. 90, no 2, p. 151-151Conference paper (Refereed)
    Abstract [en]

    Introduction: We have recently observed (Svensson et al., data to be published) that M-CSF and IL-10, among several factors tested, are able to induce macrophages (MΦ) with phenotypic characteristics of decidual MΦ with expression of typical M2, or immune regulatory, cell surface markers (scavenger receptor, mannose receptor, DC-SIGN). The aim of this study was to investigate in a comprehensive manner whether this finding could be shown by an extended mapping of secreted molecules and also at the gene expression level.

    Materials and methods: CD14+ blood monocytes and decidual MΦ from healthy first trimester pregnant women (n = 11) were isolated by immunomagnetic cell sorting (MACS). MΦ were also generated in vitro from MACS-sorted CD14+ blood monocytes from non-pregnant women. RNA was isolated from blood monocytes and MΦ and the expression of 100 decidual MΦ-associated genes (Gustafsson et al., PlosOne 2008) was analysed with a custom microarray. RT-PCR was used to analyse the gene expression of IRF5, which was recently associated with classically activated (M1) MΦ. A multiplex bead assay was used to quantify the levels of cytokines and chemokines in conditioned media.

    Results: To estimate the similarity of the in vitro differentiated MΦ with decidual MΦ, we performed hierarchical clustering of differentially regulated genes. M1 MΦ and MΦ treated with GM-CSF and IL-4/13 formed their own branches, indicating transcriptional profiles clearly differing from all other MΦ types analysed. MΦ differentiated with M-CSF alone or with IL-10, regardless of the growth factor used, clustered together with decidual MΦ, supporting their close relationship. Genes similarly regulated in these macrophages were not restricted to immune modulating genes. This group included the M2-associated chemokines CCL2 and CCL18, the immune modulating B7 family-related VSIG4, the angiogenic insulin-like growth factor-1 and the M2-associated folate receptor β-encoding FOLR2 and selenoprotein-encoding SEPP1. The M2 polarisation status of decidual MΦ was confirmed by low expression of the M1-associated transcription factor IRF5, and comparable levels were detected in M-CSF- and IL-10-stimulated MΦ. IRF5 expression was higher in M1 MΦ and, surprisingly, also in IL-4/13-stimulated MΦ. As to protein secretion, decidual and M-CSF/IL-10-stimulated MΦ were found to produce comparable levels of IL-10 and the pro-inflammatory cytokines IL-6 and TNF, while M1 MΦ produced significantly higher levels of TNF and did not produce IL-10. Decidual and M-CSF/IL-10-stimulated MΦ also produced high levels of the monocyte- and granulocyte-recruiting chemokines CCL2, CCL4 and CXCL1, while the Th1 cell-recruiting CXCL10 and the Th2 cell-recruiting CCL22 were only produced at low levels. CXCL10 was highest in M1 MΦ, while CCL22 levels were highest in GM-CSF and/or IL-4/13-stimulated MΦ.

    Conclusions: Our data consistently shows a central role for M-CSF and IL-10 as polarising agents for decidual MΦ, while Th2 and pro-inflammatory agents induce MΦ with clearly differing characteristics. We hypothesise that decidual MΦ have a predominant homeostatic function. This is supported by their low production of both Th1 and Th2 cell-recruiting chemokines. It is thus likely that M-CSF and IL-10 shape the polarisation of decidual MΦ contributing to the homeostatic and tolerant immune environment required for successful fetal development.

  • 112.
    Svensson, Judit
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Matussek, Andreas
    County Hospital Ryhov.
    Geffers, Robert
    Helmholtz Centre Infect Research.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Macrophages at the fetal-maternal interface express markers of alternative activation and are induced by M-CSF and IL-102011In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 187, no 7, p. 3671-3682Article in journal (Refereed)
    Abstract [en]

    During pregnancy, the maternal immune system is challenged by the presence of the fetus, which must be tolerated despite being semiallogeneic. Uterine mucosal (or decidual) macrophages (Mϕ), one of the major leukocyte populations at the fetal–maternal interface, have been implicated in fetal tolerance, but information regarding their regulation is scarce. In this study, we investigated the role of several factors potentially involved in the differentiation and polarization of decidual Mϕ with an in vitro Mϕ differentiation model. By using flow cytometry, we showed that M-CSF and IL-10 were potent inducers of M2 (immunoregulatory) Mϕ markers expressed on human decidual Mϕ (CD14, CD163, CD206, CD209). In contrast, proinflammatory stimuli, and unexpectedly also the Th2-associated IL-4 and IL-13, induced different patterns of expression, indicating that a Th2-dominated environment is not required for decidual Mϕ polarization. M-CSF/IL-10–stimulated and decidual Mϕ also showed similar cytokine secretion patterns, with production of IL-10 as well as IL-6, TNF, and CCL4. Conversely, the proinflammatory, LPS/IFN-γ–stimulated Mϕ produced significantly higher levels of TNF and no IL-10. We also used a gene array with 420 Mϕ-related genes, of which 100 were previously reported to be regulated in a global gene expression profiling of decidual Mϕ, confirming that M-CSF/IL-10–induced Mϕ are closely related to decidual Mϕ. Taken together, our results consistently point to a central role for M-CSF and in particular IL-10 in the shaping of decidual Mϕ with regulatory properties. These cytokines may therefore play an important role in supporting the homeostatic and tolerant immune milieu required for a successful pregnancy.

  • 113.
    Szymanowski, Aleksander
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Backteman, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental 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 Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    T CELL ACTIVATION AND APOPTOSIS IN CORONARY ARTERY DISEASE2009In: ATHEROSCLEROSIS SUPPLEMENTS, Elsevier, 2009, Vol. 10, no 2, p. e931-e931Conference paper (Other academic)
  • 114.
    Szymanowski, Alexander
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Backteman, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental 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 Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    T cell activitation and apoptosis in coronary artery disease.2009Conference paper (Refereed)
  • 115.
    Tedeholm, H
    et al.
    Sahlgrens University Hospital, Sweden .
    Lycke, J
    Sahlgrens University Hospital, Sweden .
    Skoog, B
    Sahlgrens University Hospital, Sweden .
    Lisovskaja, V
    Chalmers, Sweden .
    Hillert, J
    Karolinska University Hospital, Sweden .
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Fagius, J
    Karolinska University Hospital, Sweden .
    Fredrikson, S
    Karolinska University Hospital, Sweden .
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Malmestrom, C
    Sahlgrens University Hospital, Sweden .
    Martin, C
    University Hospital, Sweden .
    Piehl, F
    Karolinska University Hospital, Sweden .
    Runmarker, B
    Sahlgrens University Hospital, Sweden .
    Stawiarz, L
    Karolinska University Hospital, Sweden .
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Nerman, O
    Chalmers, Sweden .
    Andersen, O
    Sahlgrens University Hospital, Sweden .
    Time to secondary progression in patients with multiple sclerosis who were treated with first generation immunomodulating drugs2013In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 6, p. 765-774Article in journal (Refereed)
    Abstract [en]

    Background: It is currently unknown whether early immunomodulatory treatment in relapsing-remitting MS (RRMS) can delay the transition to secondary progression (SP). less thanbrgreater than less thanbrgreater thanObjective: To compare the time interval from onset to SP in patients with RRMS between a contemporary cohort, treated with first generation disease modifying drugs (DMDs), and a historical control cohort. less thanbrgreater than less thanbrgreater thanMethods: We included a cohort of contemporary RRMS patients treated with DMDs, obtained from the Swedish National MS Registry (disease onset between 1995-2004, n = 730) and a historical population-based incidence cohort (onset 1950-64, n = 186). We retrospectively analyzed the difference in time to SP, termed the "period effect" within a 12-year survival analysis, using Kaplan-Meier and Cox regression analysis. less thanbrgreater than less thanbrgreater thanResults: We found that the "period" affected the entire severity spectrum. After adjusting for onset features, which were weaker in the contemporary material, as well as the therapy initiation time, the DMD-treated patients still exhibited a longer time to SP than the controls (hazard ratios: men, 0.32; women, 0.53). less thanbrgreater than less thanbrgreater thanConclusion: Our results showed there was a longer time to SP in the contemporary subjects given DMD. Our analyses suggested that this effect was not solely driven by the inclusion of benign cases, and it was at least partly due to the long-term immunomodulating therapy given.

  • 116.
    Thegerström, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Mycobacterium avium infections in children2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Mycobacterium avium belongs to a group of over 130 species of non-tuberculous mycobacteria (NTM) or environmental mycobacteria. The subspecies Mycobacterium avium avium was originally described as the causative agent of bird tuberculosis, but was later found to cause disease also in humans. Small children display a special form of infection that is seldom detected in other age groups. It manifests as a chronic lymphadenitis usually in the head and neck region. The incidence rate is approximately 1-5/100,000 children/year. However, exposure to this bacterium is high as judged by sensitin skin test studies. Even if a lot of persons are infected with M. avium, a majority of them do not develop disease and the bacterium is therefore considered to be of low virulence, causing disease mainly in immunocompromised persons. Children with M. avium lymphadenitis, however, usually do not have any known deficiencies in the immune system.

    This thesis elucidates why small children are prone to develop disease by M. avium. Investigation of a possible zoonotic spread of this bacterium to children involved analysis and comparison of different strains isolated from birds and other animals and from children, using the restriction fragment length polymorphism (RFLP) method on insertion sequence IS1245, resulting in the finding that the children were infected exclusively with the new proposed subspecies M. avium hominissuis. Animals in general and birds in particular were infected with the subspecies M. avium avium (using the more narrow definition). Moreover, when investigating the immunological response of human peripheral blood mononuclear cells (PBMCs) to stimulation with M. avium hominissuis and M. avium avium, respectively, it was found that the former subspecies induced lower IFN-γ and IL-17 than the latter, but higher levels of Il-10, which might contribute to explain the higher pathogenicity of M. avium hominissuis in humans.

    Through studies of the geographical distribution of cases of M. avium infection in children in Sweden and the seasonal variation of the disease, a fluctuation of the incidence over the year was detected, with higher numbers of cases in the autumn months and lower numbers in the late spring. There was a higher incidence rate in children living close to water than in those living in the inland or in the urban areas. Therefore, outdoor natural water is the most probable source of infection in children with M. avium lymphadenitis. Through a descriptive clinical retrospective study, complete surgical removal of the affected lymph node was found to lead to better results than treatment by incision and drainage of abscess or expectation only.

    Finally there might be several explanations as to why an individual develops disease after infection with M. avium, such as, exposure, bacterial virulence factors or possible specific deficiencies of the immune system of the host or a combination of these factors. Which are the more important factors regarding children with M. avium lymphadenitis is still an open question.

    List of papers
    1. Mycobacterium avium with the bird type IS1245 RFLP profile is commonly found in wild and domestic animals, but rarely in humans
    Open this publication in new window or tab >>Mycobacterium avium with the bird type IS1245 RFLP profile is commonly found in wild and domestic animals, but rarely in humans
    Show others...
    2005 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 37, no 1, p. 15-20Article in journal (Refereed) Published
    Abstract [en]

    Cervical lymphadenitis is the main manifestation of Mycobacterium avium infection in immunocompetent children. Exposure to birds has been discussed as a source of infection. To clarify from where children acquire the infection, M. avium isolates from different origins were analysed with restriction fragment length polymorphism (RFLP) on insertion sequence IS1245, and compared by computer cluster correlation analysis. This molecular epidemiological tool has previously revealed a distinction between multiband profiles found mainly in strains from humans, and a 3-band/bird type profile in strains isolated mainly from birds. 32 isolates from children were compared with 28 isolates from adults and 45 isolates from animals. We found that 67% of the animal isolates had the bird type profile, also found in 1 sputum isolate from an adult. Strains from children showed only multiband profiles that did not differ significantly from profiles of isolates from adults. All but 2 bird isolates showed the bird type profile. Neither of the remaining 2, which had multiband profiles, clustered with the isolates from children. Our results indicate that the true reservoir of M. avium. is unknown. Thus the question of whether or not M. avium can be incriminated as a zoonotic disease remains unanswered. © 2005 Taylor & Francis.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-37021 (URN)10.1080/00365540510026850 (DOI)33487 (Local ID)33487 (Archive number)33487 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
    2. Mycobacterium avium lymphadenopathy among children, Sweden
    Open this publication in new window or tab >>Mycobacterium avium lymphadenopathy among children, Sweden
    Show others...
    2008 (English)In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 14, no 4, p. 661-663Article in journal (Refereed) Published
    Abstract [en]

    We studied Mycobacterium avium lymphadenopathy in 183 Swedish children (<7 years of age) from 1998 through 2003. Seasonal variation in the frequency of the disease, with a peak in October and a low point in April, suggests cyclic environmental factors. We also found a higher incidence of the disease in children who live close to water.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-44944 (URN)10.3201/eid1404.060570 (DOI)78351 (Local ID)78351 (Archive number)78351 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
    3. Clinical features and incidence of Mycobacterium avium infections in children
    Open this publication in new window or tab >>Clinical features and incidence of Mycobacterium avium infections in children
    Show others...
    2008 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 40, no 6-7, p. 481-486Article in journal (Refereed) Published
    Abstract [en]

    Mycobacterium avium is the most common pathogen in children presenting as non-tuberculous mycobacterial lymphadenitis. In Sweden non-tuberculous mycobacterial infection is a notifiable disease. The goal of our study was to determine the annual incidence of M. avium infection in Swedish children, 1998-2003, and describe clinical features related to age and treatment of children with M. avium lymphadenitis. To do this, we retrospectively analysed patient records of 162 children less than 7 y of age from the entire country with culture-verified M. avium disease. The incidence of M. avium infection in Sweden was lower in 2000-2003 than in 1998-1999. Young children (≤24 months old) had more constitutional symptoms at onset of disease than older children. One-third of the children had received 2 or more antibiotic courses before diagnosis. Disfiguring scars after healing were more common in children who were not treated with surgical extirpation of the affected lymph nodes. The decreasing incidence of M. avium infection among Swedish children in recent y is in contrast to reports of increasing non-tuberculous mycobacterial disease from other countries. Our results support the view that M. avium lymphadenitis should be treated by surgical removal of the affected tissue.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-44945 (URN)10.1080/00365540701840088 (DOI)78352 (Local ID)78352 (Archive number)78352 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
    4. Mycobacterium avium avium and Mycobacterium avium hominissuis give different cytokine responses after in vitro stimulation of human blood mononuclear cells
    Open this publication in new window or tab >>Mycobacterium avium avium and Mycobacterium avium hominissuis give different cytokine responses after in vitro stimulation of human blood mononuclear cells
    Show others...
    2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 4, p. e34391-Article in journal (Refereed) Published
    Abstract [en]

    Background: Mycobacterium avium is the principal etiologic agent of non-tuberculous lymphadenitis in children. It is also a known pathogen for birds and other animals. Molecular epidemiologic evidence indicates that humans and animals are infected with different M. avium subspecies, namely, M. avium subsp. avium and M. avium subsp. hominissuis, respectively.

    Aim: To investigate the effect on the human immune system of 10 isolates of M. avium subsp. avium mainly isolated from animals and of 11 isolates of M. avium subsp. hominissuis isolated from children with lymphadenitis.

    Method: Peripheral blood mononuclear cells (PBMC) from six healthy blood donors were stimulated in vitro with the inactivated mycobacteria followed by quantification of IL-10, IL-12p70, TNF, IFN-γ and IL-17 in supernatants by multiplex bead array analysis (Luminex).

    Results: M. avium subsp. hominissuis induced significantly more IL-10 and significantly less IL-12p70, TNF, IFN-γ and IL-17 compared to M. avium subsp. avium. All strains induced high levels of IL-17, but very little IL-12.

    Conclusion: The lower T helper (Th) 1 and Th17 responses induced by M. avium subsp. hominissuis compared to M. avium subsp. avium after in vitro stimulation of PBMC might contribute to its higher pathogenicity in humans.

    Place, publisher, year, edition, pages
    PloS, 2012
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-53785 (URN)10.1371/journal.pone.0034391 (DOI)000305297500026 ()
    Available from: 2010-02-03 Created: 2010-02-03 Last updated: 2017-12-12
  • 117.
    Thegerström, Johanna
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology .
    Friman, V
    Nylen, O
    Romanus, V
    Olsen, B
    Clinical features and incidence of Mycobacterium avium infections in children2008In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 40, no 6-7, p. 481-486Article in journal (Refereed)
    Abstract [en]

    Mycobacterium avium is the most common pathogen in children presenting as non-tuberculous mycobacterial lymphadenitis. In Sweden non-tuberculous mycobacterial infection is a notifiable disease. The goal of our study was to determine the annual incidence of M. avium infection in Swedish children, 1998-2003, and describe clinical features related to age and treatment of children with M. avium lymphadenitis. To do this, we retrospectively analysed patient records of 162 children less than 7 y of age from the entire country with culture-verified M. avium disease. The incidence of M. avium infection in Sweden was lower in 2000-2003 than in 1998-1999. Young children (≤24 months old) had more constitutional symptoms at onset of disease than older children. One-third of the children had received 2 or more antibiotic courses before diagnosis. Disfiguring scars after healing were more common in children who were not treated with surgical extirpation of the affected lymph nodes. The decreasing incidence of M. avium infection among Swedish children in recent y is in contrast to reports of increasing non-tuberculous mycobacterial disease from other countries. Our results support the view that M. avium lymphadenitis should be treated by surgical removal of the affected tissue.

  • 118.
    Thegerström, Johanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Jönsson, B.
    Department of Infectious Medicine, Institute of Biomedicine, University of Gothenburg, Sweden.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Olsen, B.
    Infectious Diseases, Department of Medical Sciences, Uppsala University and Academic Hospital, Uppsala, Sweden.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Friman, V.
    Department of Infectious Diseases, Sahlgrenska University Hospital/Östra, University of Gothenburg, Sweden.
    Mycobacterium avium avium and Mycobacterium avium hominissuis give different cytokine responses after in vitro stimulation of human blood mononuclear cells2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 4, p. e34391-Article in journal (Refereed)
    Abstract [en]

    Background: Mycobacterium avium is the principal etiologic agent of non-tuberculous lymphadenitis in children. It is also a known pathogen for birds and other animals. Molecular epidemiologic evidence indicates that humans and animals are infected with different M. avium subspecies, namely, M. avium subsp. avium and M. avium subsp. hominissuis, respectively.

    Aim: To investigate the effect on the human immune system of 10 isolates of M. avium subsp. avium mainly isolated from animals and of 11 isolates of M. avium subsp. hominissuis isolated from children with lymphadenitis.

    Method: Peripheral blood mononuclear cells (PBMC) from six healthy blood donors were stimulated in vitro with the inactivated mycobacteria followed by quantification of IL-10, IL-12p70, TNF, IFN-γ and IL-17 in supernatants by multiplex bead array analysis (Luminex).

    Results: M. avium subsp. hominissuis induced significantly more IL-10 and significantly less IL-12p70, TNF, IFN-γ and IL-17 compared to M. avium subsp. avium. All strains induced high levels of IL-17, but very little IL-12.

    Conclusion: The lower T helper (Th) 1 and Th17 responses induced by M. avium subsp. hominissuis compared to M. avium subsp. avium after in vitro stimulation of PBMC might contribute to its higher pathogenicity in humans.

  • 119.
    Thegerström, Johanna
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology.
    Romanus, V
    Friman, V
    Brudin, L
    Haemig, P D
    Olsen, B
    Mycobacterium avium lymphadenopathy among children, Sweden2008In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 14, no 4, p. 661-663Article in journal (Refereed)
    Abstract [en]

    We studied Mycobacterium avium lymphadenopathy in 183 Swedish children (<7 years of age) from 1998 through 2003. Seasonal variation in the frequency of the disease, with a peak in October and a low point in April, suggests cyclic environmental factors. We also found a higher incidence of the disease in children who live close to water.

  • 120.
    Tisell, Anders
    et al.
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL.
    Mellergård, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL.
    Brain Atrophy in MS Patients Correlates with Creatine Concentrations2012Conference paper (Other academic)
  • 121.
    Tisell, Anders
    et al.
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL.
    Mellergård, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Department of Medical Specialist.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Radiology in Linköping.
    Increased Glia in Multiple Sclerosis Patients Correlates with Intrathecal Inflammation2011Conference paper (Refereed)
  • 122.
    Tisell, Anders
    et al.
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiation Physics. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL. Linköping University, Faculty of Health Sciences.
    Mellergård, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Department of Medical Specialist.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Radiology in Linköping.
    Multiple Sclerosis Severity Score (MSSS) Correlates With Changes in NAWM Metabolism During Treatment2011Conference paper (Refereed)
  • 123.
    Tjernberg, Ivar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Carlsson, Martin
    Kalmar County Hospital.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Eliasson, Ingvar
    NAL, Trollhattan, Sweden .
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Mapping of hormones and cortisol responses in patients after Lyme neuroborreliosis2010In: BMC INFECTIOUS DISEASES, ISSN 1471-2334, Vol. 10, no 20Article in journal (Refereed)
    Abstract [en]

    Background: Persistent symptoms after treatment for neuroborreliosis are common for reasons mainly unknown. These symptoms are often unspecific and could be caused by dysfunctions in endocrine systems, an issue that has not been previously addressed systematically. We therefore mapped hormone levels in patients with previous confirmed Lyme neuroborreliosis of different outcomes and compared them with a healthy control group. Methods: Twenty patients of a retrospective cohort of patients treated for definite Lyme neuroborreliosis were recruited 2.3 to 3.7 years (median 2.7) after diagnosis, together with 23 healthy controls. Lyme neuroborreliosis patients were stratified into two groups according to a symptom/sign score. All participants underwent anthropometric and physiological investigation as well as an extensive biochemical endocrine investigation including a short high-dose adrenocorticotropic hormone stimulation (Synacthen (R)) test. In addition to hormonal status, we also examined electrolytes, 25-hydroxy-vitamin D and interleukin-6. Results: Eight patients (40%) had pronounced symptoms 2-3 years after treatment. This group had a higher cortisol response to synacthen as compared with both controls and the Lyme neuroborreliosis patients without remaining symptoms (p andlt; 0.001 for both comparisons). No other significant differences in the various baseline biochemical parameters, anthropometric or physiological data could be detected across groups. Conclusions: Apart from a positive association between the occurrence of long-lasting complaints after Lyme neuroborreliosis and cortisol response to synacthen, no corticotropic insufficiency or other serious hormonal dysfunction was found to be associated with remaining symptoms after treatment for Lyme neuroborreliosis.

  • 124.
    Tjernberg, Ivar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Henningsson, Anna J
    Ryhov County Hospital.
    Eliasson, Ingvar
    Norra Älvsborgs Länssjukhus.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Diagnostic performance of cerebrospinal fluid chemokine CXCL13 and antibodies to the C6-peptide in Lyme neuroborreliosis.2011In: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 62, no 2, p. 149-158Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The aim of this study was to evaluate the chemokine CXCL13 and C6 antibodies separately and in combination in paired serum/cerebrospinal fluid (CSF) samples in the laboratory diagnosis of Lyme neuroborreliosis (LNB).

    METHODS: A large retrospective material with paired serum/CSF samples from 261 patients with clinically suspected LNB was investigated. Patients were divided into three main diagnostic groups based on original results of CSF pleocytosis and intrathecal anti-borrelia antibodies (purified flagellum). Levels of CXCL13, albumin, total IgM and IgG in paired samples and C6 antibodies in CSF were compared across diagnostic groups.

    RESULTS: A sensitivity of 99% and a specificity of 96% were achieved for CSF-Serum CXCL13 ratio. CSF-C6 antibodies performed with a sensitivity of 99% and a specificity of 88.0%. A combination of CSF-Serum CXCL13 ratio and CSF-C6 antibodies, evaluated in parallel, revealed a sensitivity of 99% and specificity of 98%.

    CONCLUSIONS: This study confirms CSF-CXCL13 as a reliable marker of LNB and suggests improved diagnostic performance especially in children with possible LNB.

  • 125.
    Tjernberg, Ivar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases .
    Schön, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology .
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Carlsson-Wistedt, Annika
    Clinical Microbiology Kalmar County Hospital, Kalmar.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Eliasson, Ingvar
    Department of Clinical Microbiology and Immunology Lund University Hospital.
    C6-peptide serology as diagnostic tool in neuroborreliosis2008In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 116, no 5, p. 393-399Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate the usefulness of borrelia serology (Quick ELISA C6 Borrelia assay kit) as a diagnostic tool in cases of suspected neuroborreliosis. A retrospective patient material consisting of 124 paired serum and cerebrospinal fluid samples with a positive anti-borrelia antibody index (AI) using the IDEIA Lyme Neuroborreliosis test was compared with 124 AI-negative matched control subjects. The patients were divided into four groups based on presence of pleocytosis and age above or below 12 years. The presence of positive C6 serology in AI-positive patients with pleocytosis was 89% (83/93), significantly different (p<0.01) from in patients without pleocytosis (58%, 18/31). In AI-positive patients aged ≥12 years with pleocytosis, 94% (51/54) had a positive C6 serology. Of AI-positive patients with a symptom duration of more than 30 days, 93% (27/29) were positive by the C6 test. We conclude that the C6 serum test, together with clinical evaluation, is a powerful diagnostic tool in adult (≥12 years) European patients with suspected neuroborreliosis with a symptom duration of more than 30 days. Patients with suspected neuroborreliosis and positive C6 results should be further investigated by lumbar puncture for definite diagnosis. © The Authors 2008.

  • 126.
    Vrethem, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Lindvall, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Subacute neuronopathy in a young man: a possible association with tetracycline treatment2011In: Neurology international, ISSN 2035-8377, Vol. 3, no 3, p. e16-Article in journal (Refereed)
    Abstract [en]

    A young man with subacute neuronopathy following tetracycline treatment is described. The symptoms started as a sensory dorsal root affection but by time also involved motor nerves. He developed a severe sensory ataxia with pseudoathetotic movements. Other possible aetiologies were scrutinized and excluded. Tetracycline induced neuronopathy is hitherto not reported in the literature. We propose a possible association between treatment with tetracycline and the development of sensory neuronopathy in this patient.

  • 127.
    Vrethem, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Kvarnström, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Stenstam, J
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Cassel, Petra
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Gustafsson, M
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Department of Medical Specialist.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Cytokine mapping in cerebrospinal fluid and blood in multiple sclerosis patients without oligoclonal bands2012In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 18, no 5, p. 669-673Article in journal (Refereed)
    Abstract [en]

    Objective: Since there are clinical and genetic differences between MS patients with intrathecal oligoclonal bands (OCB+ ) in the cerebrospinal fluid (CSF) compared with those without (OCB-), the aim was to find out if OCB- patients showed a different pattern of cytokine immune activation compared with OCB+ patients. Methods: The study included 25 MS patients (10 OCB- and 15 OCB+ ) and 13 controls. A panel of cytokines was measured; IL-1β, IL-6, IL-8/CXCL8, IL-10, TNF and GM-CSF in serum, CSF and in supernatants from polyclonally stimulated blood mononuclear cells, where also levels of IL-12p40, IL-13, IL-15, IL-17 and IFN-γ were measured. The concentrations of soluble (s) VCAM-1 and sCD14 were measured in serum and CSF. Results: In general, there were no extensive differences in cytokine concentrations between the OCB- and OCB+ groups. Conclusion: OCB- MS patients do not seem to constitute a separate entity concerning inflammatory parameters measured as cytokine concentrations in CSF and blood.

  • 128.
    Vrethem, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Lindh, J
    Ryhov County Hospital, Sweden .
    Tondel, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Persson, B
    University of Gothenburg, Sweden .
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    IgA antibodies against tissue transglutaminase, endomysium and gliadin in idiopathic polyneuropathy2013In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 127, no 2, p. 109-115Article in journal (Refereed)
    Abstract [en]

    Objectives To study the prevalence of antibodies of IgA class against tissue transglutaminase (tTG), endomysium (EMA) and gliadin (AGA) in patients with chronic idiopathic axonal polyneuropathy (CIAP) and to characterize the patients clinically and neurophysiologically. Methods Of 182 patients, 126 patients agreed to blood sampling. Sera were analysed by ELISAs detecting anti-tTG and AGA, whereas EMA was analysed by indirect immunofluorescence (IF) microscopy. Gastrointestinal symptoms were assessed by data from medical records and patient interviews. Results Nine of 126 patients (7%) were seropositive in at least one test (five with positive anti-tTG and/or EMA and four with positive AGA only). One patient with elevated levels of all specificities had laboratory signs of malabsorption and gastrointestinal complaints with abdominal pain and diarrhoea. Conclusions Elevated levels of IgA-AGA were slightly more frequent in patients with CIAP (4%) compared to 2.5% in 1866 healthy blood donors. Highly specific serological markers indicative of coeliac disease (CD) (anti-tTG and EMA) were somewhat more common in our patients with CIAP (4%) than expected from normal reference values and from studies of the prevalence of CD in the general population. Even though these findings may indicate a relationship, the aetiological importance is unclear.

  • 129.
    Vrethem, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Widhe, Mona
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Garpmo, Ulf
    Kalmar Hospital.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Clinical, diagnostic and immunological characteristics of patients with possible neuroborreliosis without intrathecal Ig-synthesis against Borrelia antigen in the cerebrospinal fluid2011In: Neurology International, ISSN 2035-8385, E-ISSN 2035-8377, Vol. 3, no 1, article id e2Article in journal (Refereed)
    Abstract [en]

    The diagnosis of neuroborreliosis is not always straightforward. Intrathecal immunoglobulin (Ig) synthesis against Borrelia antigen may not be detected, at least early in the disease course. Also other neurological and infectious diagnoses have to be considered. We have studied patients with clinical possible neuroborreliosis without intrathecal Ig synthesis against Borrelia antigen in the cerebrospinal fluid (CSF) (n=17). Diagnosis was based on typical clinical history and at least one of the following findings; mononuclear leucocytosis in the CSF (n=4); typical erythema migrans >5 cm in diameter in relation to debut of symptoms (n=8); prompt clinical response to antibiotic teratment (n=14). Also other possible diagnoses had to be excluded. Seventeen patients first investigated because of suspected neuroborreliosis but later confirmed with other diagnoses were used as controls. All patients had a lumbar puncture. Borrelia specific IFN-γ and IL-4 secretion was investigated in peripheral blood (PBL) and CSF with an ELISPOT assay. Polymerase chain reaction (PCR) was used to reveal any Borrelia antigen in the CSF. Six of 17 patients with possible neuroborreliosis showed high IFN-g secretion in peripheral blood, otherwise we found no statistically significant differences between the groups. PCR did not reveal any Borrelia antigen in CSF. The diagnosis and treatment of possible but not confirmed neuroborreliosis is a clinical challenge. The clinical response to treatment may be the best option in these cases.

  • 130.
    Wang, Ning
    et al.
    Karolinska Institute.
    Shen, Nan
    Jiao Tong University.
    Vyse, Timothy J.
    Hammersmith Hospital.
    Anand, Vidya
    Hammersmith Hospital.
    Gunnarson, Iva
    Karolinska University Hospital Solna.
    Sturfelt, Gunnar
    University of Lund Hospital.
    Rantapaa-Dahlqvist, Solbritt
    Umeå University Hospital.
    Elvin, Kerstin
    Karolinska University Hospital Huddinge.
    Truedsson, Lennart
    Lund University.
    A. Andersson, Bengt
    Sahlgrens Academy.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Ortqvist, Eva
    Karolinska University Hospital Solna.
    K. Gregersen, Peter
    Feinstein Institute Medical Research.
    W. Behrens, Timothy
    Genentech Inc.
    Hammarstrom, Lennart
    Karolinska Institute.
    Selective IgA Deficiency in Autoimmune Diseases2011In: Molecular medicine (Cambridge, Mass. Print), ISSN 1076-1551, E-ISSN 1528-3658, Vol. 17, no 11, p. 1383-1396Article, review/survey (Refereed)
    Abstract [en]

    Selective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in Caucasians. It has previously been suggested to be associated with a variety of concomitant autoimmune diseases. In this review, we present data on the prevalence of IgAD in patients with Graves disease (GD), systemic lupus erythematosus (SLE), type 1 diabetes (T1D). celiac disease (CD), myasthenia gravis (MG) and rheumatoid arthritis (RA) on the basis of both our own recent large-scale screening results and literature data. Genetic factors are important for the development of both IgAD and various autoimmune disorders, including GD, SLE, T1D, CD, MG and RA, and a strong association with the major histocompatibility complex (MHC) region has been reported. In addition, non-MHC genes, such as interferon-induced helicase 1 (IFH1) and c-type lectin domain family 16, member A (CLEC16A), are also associated with the development of IgAD and some of the above diseases. This indicates a possible common genetic background. In this review, we present suggestive evidence for a shared genetic predisposition between these disorders.

  • 131.
    Widhe, Mona
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Jarefors, Sara
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Hedin-Skogman, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Peterson, E. M.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Bergstrom, S.
    University of Umeå.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    T-Cell Epitope Mapping of the Borrelia garinii Outer Surface Protein A in Lyme Neuroborreliosis2009In: SCANDINAVIAN JOURNAL OF IMMUNOLOGY, ISSN 0300-9475, Vol. 70, no 2, p. 141-148Article in journal (Refereed)
    Abstract [en]

    We studied the T-cell reactivity to overlapping peptides of B. garinii OspA, in order to locate possible immunodominant T-cell epitopes in neuroborreliosis. Cells from cerebrospinal fluid (CSF) and blood from 39 patients with neuroborreliosis and 31 controls were stimulated with 31 overlapping peptides, and interferon-gamma secreting cells were detected by ELISPOT. The peptides OspA(17-36), OspA(49-68), OspA(105-124), OspA(137-156), OspA(193-212) and OspA(233-252) showed the highest frequency of positive responses, being positive in CSF from 38% to 50% of patients with neuroborreliosis. These peptides also elicited higher responses in CSF compared with controls (P = 0.004). CSF cells more often showed positive responses to these peptides than blood cells (P = 0.001), in line with a compartmentalization to the central nervous system. Thus, a set of potential T-cell epitopes were identified in CSF cells from patients with neuroborreliosis. Further studies may reveal whether these epitopes can be used diagnostically and studies involving HLA interactions may show their possible pathogenetic importance.

  • 132.
    Widhe, Mona
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Grusell, Mattias
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. 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 Clinical and Experimental Medicine, Neurology. Linköping University, Department of Neuroscience and Locomotion, Neurophysiology. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Cytokines in Lyme borreliosis: lack of early tumour necrosis factor-α and transforming growth factor-β1 responses are associated with chronic neuroborreliosis2002In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 107, no 1, p. 46-55Article in journal (Refereed)
    Abstract [en]

    The clinical outcome of the tick born infection Lyme borreliosis seems to be influenced by the type of immune response mounted during the disease, as suggested by various animal models. Here we report the serum and cerebrospinal fluid levels of tumour necrosis factor-α (TNF-α), transforming growth factor β1 (TGF-β1) and interleukin-6 (IL-6) in samples drawn at different disease intervals during the course of non-chronic neuroborreliosis (n=10), chronic neuroborreliosis (n=15), erythema migrans (n=8, serum only) and controls (n=7). When comparing early neuroborreliosis cerebrospinal fluid samples, significantly higher levels of TNF-α were found in non-chronic patients than in chronic patients (P<0·05). Moreover, TGF-β1 was increased in the early serum samples of non-chronic patients, as compared to chronic patients (P<0·01). Elevated serum levels of TGF-β1 were also found in erythema migrans as compared to neuroborreliosis and controls (P<0·05). The high TNF-α levels noted in early cerebrospinal fluid samples of non-chronic patients only, possibly reflects an ongoing pro-inflammatory immune response in the central nervous system, which could be beneficial in eliminating disease. High serum levels of TGF-β1 probably mirror an anti-inflammatory response, which might play a role in controlling the systemic immune response.

  • 133.
    Widhe, Mona
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Hedin Skogman, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Bergström, Sven
    Department of Microbiology, University of Umeå, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Jarefors, Sara
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Eknefelt, Mattias
    Pediatric Clinic, Ryhov County Hospital, Jönköping, Sweden.
    Eneström, Gunilla
    Pediatric Clinic, Västervik Hospital, Västervik, Sweden.
    Nordwall, Maria
    Pediatric Clinic, Vrinnevi Hospital, Norrköping, Sweden.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Croner, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Up-regulation of Borrelia-specific IL-4 and IFN-gamma secreting cells in cerebrospinal fluid from children with Lyme neuroborreliosis2005In: International Immunology, ISSN 0953-8178, Vol. 17, no 10, p. 1283-1291Article in journal (Refereed)
    Abstract [en]

    The clinical course and outcome of several infectious diseases are dependent on the type of immune response elicited against the pathogen. In adults with neuroborreliosis (NB), a type 1 response with high production of Borrelia-specific IFN-, but no IL-4, has been reported. Since children have a more benign course of NB than adults, we wanted to investigate type 1 and type 2 responses in children with NB. Cerebrospinal fluid (CSF) and blood were collected from children during the acute stage of ‘confirmed NB’ (n = 34), ‘possible NB’ (n = 30) and ‘non-NB’ (n = 10). The number of Borrelia-specific IL-4- and IFN--secreting cells was measured by enzyme-linked immunospot assay. Borrelia-specific secretion of both IL-4 and IFN- was increased in CSF in confirmed (P < 0.05) and possible (P < 0.01) NB, when compared with non-NB controls. Furthermore, children with NB had significantly higher Borrelia-specific IL-4 secretion in CSF than an adult reference material with NB (P < 0.05). There were no differences in cytokine secretion in relation to onset or recovery of neurological symptoms. Since IL-4 is known to down-regulate the pro-inflammatory and possibly harmful effects of prolonged IFN- responses, the prominent IL-4 response observed in the central nervous system compartment might contribute to the more benign disease course seen in children with Lyme NB.

  • 134.
    Widhe, Mona
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Jarefors, Sara
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. 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 Clinical and Experimental Medicine, Neurology. Linköping University, Department of Neuroscience and Locomotion, Neurophysiology. Linköping University, Faculty of Health Sciences.
    Bergström, Sven
    Department of Molecular Biology, University of Umeå, Umeå, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences.
    Borrelia-specific interferon-γ and interleukin-4 secretion in cerebrospinal fluid and blood during Lyme borreliosis in humans: association with clinical outcome2004In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 189, no 10, p. 1881-1891Article in journal (Refereed)
    Abstract [en]

    The Borrelia-specific interferon (IFN)-γ and interleukin (IL)-4 responses of 113 patients and control subjects were analyzed using the sensitive enzyme-linked immunospot method. Cerebrospinal fluid (CSF) and blood samples were obtained, during the course of disease, from patients with chronic or nonchronic neuroborreliosis (NB) and from control subjects without NB. Blood samples were obtained from patients with Lyme skin manifestations and from healthy blood donors. Early increased secretion of Borrelia-specific IFN-γ (P < .05) and subsequent up-regulation of IL-4 ( P < .05) were detected in the CSF cells of patients with nonchronic NB. In contrast, persistent Borrelia-specific IFN-γ responses were observed in the CSF cells of patients with chronic NB ( P < .05). In patients with erythema migrans, increased IFN-γ (P < .001 ) was observed in blood samples obtained early during the course of disease, whereas increased IL-4 ( P < .05) was observed after clearance. On the contrary, patients with acrodermatitis chronica atrophicans had Borrelia-specific IFN-γ (P < .001 ), but not IL-4, detected in blood samples. The present data suggest that an initial IFN-γ response, followed by up-regulation of IL-4, is associated with nonchronic manifestations, whereas a persistent IFN-γ response may lead to chronic Lyme borreliosis.

  • 135.
    Wilhelmsson, Peter
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Börjesson, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Bergström, Sven
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Erratum: Prevalence and Diversity of Borrelia Species in Ticks That Have Bitten Humans in Sweden (vol 48, pg 4169, 2010)2011In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 49, no 1, p. 481-481Article in journal (Other academic)
    Abstract [en]

    n/a

  • 136.
    Wilhelmsson, Peter
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Börjesson, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Bergström, Sven
    Umeå University.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Prevalence and Diversity of Borrelia Species in Ticks That Have Bitten Humans in Sweden2010In: JOURNAL OF CLINICAL MICROBIOLOGY, ISSN 0095-1137, Vol. 48, no 11, p. 4169-4176Article in journal (Refereed)
    Abstract [en]

    Members of the genus Borrelia are among the most common infectious agents causing tick-borne disease in humans worldwide. Here, we developed a Light Upon eXtension (LUX) real-time PCR assay that can detect and quantify Borrelia species in ticks that have fed on humans, and we applied the assay to 399 such ticks. Borrelia PCR-positive ticks were identified to species level by sequencing the products of conventional PCR performed using Borrelia group-specific primers. There was a 19% prevalence of Borrelia spp. in the detached ticks, and the number of spirochetes per Borrelia PCR-positive tick ranged from 2.0 x 10(2) to 4.9 x 10(5), with a median of 7.8 x 10(3) spirochetes. Adult ticks had a significantly larger number of spirochetes, with a median of 8.4 x 10(4) compared to the median of nymphs of 4.4 x 10(4). Adult ticks also exhibited a higher prevalence of Borrelia (33%) than nymphs (14%). Among the identified species, Borrelia afzelii was found to predominate (61%) and was followed by B. garinii (23%), B. valaisiana (13%), B. burgdorferi sensu stricto (1%), B. lusitaniae (1%), and B. miyamotoi-like (1%). Also, 3% of the ticks were coinfected with multiple strains of B. afzelii. Notably, this is the first report of B. lusitaniae being detected in ticks in Sweden. Our LUX real-time PCR assay proved to be more sensitive than a corresponding TaqMan assay. In conclusion, the novel LUX real-time PCR method is a rapid and sensitive tool for detection and quantification of Borrelia spp. in ticks.

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