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  • 1.
    Afoke, Anthony Okoro
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Some epidemiological aspects of insulin-dependent diabetes mellitus in Nigeria and Sweden1993Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In the western world diabetes mellitus is one of the most common severe diseases in childhood, but it is rarely seen in black African populations. However, there are very few epidemiological studies of childhood diabetes in Africa and almost nothing is known of the Nigerian population. One aim of this study was therefore to estimate the prevalence of insulin dependent diabetes (IDDM) in children and adolescents and to characterize their type of diabetes.

    A screening of almost 78,000 school children was performed and beside some already known diabetic patients several new cases were diagnosed. It was found that IDDM is much less common than in Europe but on the other hand more common than in several Asian countries. In addition the prevalence found may be underestimated because of cultural and social factors, health care problems and high mortality in diabetes. Although most patients had a clinical picture of Malnutrition Related Diabetes (MRD) we found in some cases autoantibodies towards islet cells and insulin and furthermore the same HLA-DQ-type-associations as seen to Type 1 diabetes in caucasian diabetics.

    While we saw no seasonal variation of diagnosis of Nigerian IDDM, there is a pronounced such seasonal variation in Sweden. This study has tried to elucidate whether this seasonal variation is related to any differences in manifestation and clinical course. Patients diagnosed during incidence peaks had more often short duration of symptoms before diagnosis,ketonuria at diagnosis, rapid loss of endogenous insulin secretion but increase of insulin antibodies and of glycosylated haemoglobin. They had also more often infections before diagnosis and high serum immunoglobulins (IgG and IgM) up to 9 months after diagnosis. HLA-DR4 was more common in these patients. The results suggest that IDDM in Swedish children is heterogenous.

  • 2. Albertsson Wikland, K
    et al.
    Alm, F
    Aronsson, S
    Gustafsson, J
    Hagenäs, L
    Häger, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Ivarsson, S
    Kriström, B
    Marcus, C
    Moell, C
    Nilsson, KO
    Ritzén, M
    Tuvemo, T
    Westergren, U
    Westphal, O
    Åman, J
    Effect of growth hormone (GH) during puberty in GH-deficient children: preliminary results from an ongoing randomized trial with different dose regimens. 1999In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 428, 80-84 p.Article in journal (Other (popular science, discussion, etc.))
  • 3.
    Aniansson Zdolsek, Helena
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Maturation of T-lymphocytes and monocytes in children in relation to development of atopic disease2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Atopic diseases have increased over the last decades in Westem countries. In order to understand the process underlying primary sensitisation to allergens we need to augment our knowledge of the maturation of T lymphocytes and monocytes in small children. The main aim was to prospectively study the development of T lymphocytes and monocytes in children who subsequently developed atopic disease.

    Material and Methods: Children (n=170) with or without an atopic family history were followed from birth to 18 months of age, and a subgroup of 38 children were followed-up also at the age of seven. The cumulative history of atopic disease was recorded. A skin prick test (SPT) was performed at 18 months and at 7 years. T-cell surface markers (CD2, 3, 4, 8, 28) were studied in all children with flow cytometry at birth, and at 18 months. These markers were also studied at 3, 6, and 12 months in a subgroup of 78 children with either strong or no atopic family history. At 18 months 54 children, 29 non-atopic and 25 atopic, were included in a functional T-cell study. Phytohaemagglutinin (PHA) or antiCD3 induced proliferation in peripheral blood mononuclear cells (PBMC) was studied by analysing 3H-thymidine incorporation. Anti-CD3 induced cytokine production (IL-4, IL-5, IL-6, IL-10, IL-13 and IFN-γ) was analysed by enzyme-linked innnuno sorbent assay (ELISA). At the age of seven 38/54 children were followed-up and the responsiveness to IL-12 was studied after stimulation with IL-2, IL-12 or both. The expression of iL-12Rß2 mRNA PBMCs was measured with real time PCR, as well as the cytokines IL-5, IL-10 and IFN-γ (ELISA). The monocyte surface marker CD14 was studied with flow cytometty in a subgroup of 76 children at bitth, 3, 6, 12 and 18 months of age, as well as soluble CD14 in serum by ELISA, and total immunoglobulin E (IgE) by UniCAP®. Soluble CDI4 (sCD14) and total lgE were also analysed in the subgroup of 38 children at seven years of age.

    Results: At 18 months 118/170 children were non-atopic and 31/170 had developed atopic disease. CD4 fluorescence intensity (Fl) on T-helper-(CD3+CD4+) cells was lower at birth and at 3 months in children with a cumulative history of atopy at 18 months than in nonatopics. Atopy was associated with a low proportion of CD2+ lymphocytes at 18 months. At this age children with a cumulative atopy and a positive SPT had lower CD2 FI, as well as lower CD3 Fl on pan T cells (CD3+CD45+CD14- cells) and higher CD28 Fl on CD2+CD8+CD28+ cells. Atopic disease at 18 months was associated with high levels of anti-CD3 induced IL-5 secretion and SPT-negative children with atopic disease produced higher levels of IL-l 0, than SPT -positive children. The IL-4/ IL-l 0 and IL-4/IFN-y ratios were higher in children with elevated total IgE levels. At age seven children with atopic aitway symptoms up-regulated the expression of IL-2 induced IL-12RP2 mRNA less than non-atopic children. This was accompanied by a low IL-2 and IL-12 induced IFN-y scretion. Fmther sCD 14 was lower at seven years in children with a cumulative histmy ofatopic disease, than in non-atopic children. This patte1n was also observed at 3 and 18 months in SPT-positive children with a cumulative histmy of atopy at 18 months compared to non-atopic SPT-negative children. In addition, children with a strong AFH had lower levels of sCD14 at 3, 12, and 18 months and at 7 years than children with no AFH.

    Conclusions: The maturation of T cells and T-cell function differs between atopic and non-atopic children. IL-12 responsiveness is reduced in children with atopic ahway symptoms and high levels of total-IgE. Altogether this may contribute to a Th2 deviated immunity in atopic disease. Atopic children have reduced levels of sCD14. The low levels may be a consequence of the atopic disease/atopic family heredity and may also reflect a reduced capacity to respond to microbial signals in atopic individuals.

    List of papers
    1. Expression of the T–cell markers CD3, CD4 and CD8 in healthy and atopic Children during the first 18 months of life
    Open this publication in new window or tab >>Expression of the T–cell markers CD3, CD4 and CD8 in healthy and atopic Children during the first 18 months of life
    Show others...
    1999 (English)In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 119, no 1, 6-12 p.Article in journal (Refereed) Published
    Abstract [en]

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

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

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

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

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25286 (URN)10.1159/000024169 (DOI)10341315 (PubMedID)9726 (Local ID)9726 (Archive number)9726 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    2. Expression of and responses to CD2 and CD3 in 18-month-old children with and without atopic dermatitis
    Open this publication in new window or tab >>Expression of and responses to CD2 and CD3 in 18-month-old children with and without atopic dermatitis
    2000 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 11, no 3, 175-182 p.Article in journal (Refereed) Published
    Abstract [en]

    We hypothesize that atopy is associated with a reduced T-cell function early in life and an imbalance in cytokine production. The purpose of this study was to investigate the expression of and responses to CD2 and CD3 in children who did or did not develop atopic dermatitis early in life. The expression of CD2 and CD3 was analyzed by flow cytometry, and proliferation of CD2 and CD3 was studied by 3H-thymidine incorporation in phytohaemagglutinin (PHA)- and anti-CD3-stimulated peripheral blood mononuclear cells (PBMC) of 18-month-old children, 25 with and 29 without atopic dermatitis. Exogenous interleukin (IL)-2 was added to compensate for possible functional differences in accessory cells. Anti-CD3-induced secretion of IL-4, IL-5, IL-6, IL-10, IL-13, and interferon-γ (IFN-γ) was analyzed by enzyme-linked immunosorbent assay (ELISA). Atopy was associated with a low proportion of CD2+ lymphocytes. Responsiveness to PHA, which activates lymphocytes partly via the sheep erythrocyte receptor, CD2, was reduced in the allergic children. The anti-CD3-induced proliferation declined more rapidly with antibody dilution in the allergic than in the non-allergic children. Atopic dermatitis was associated with high levels of anti-CD3-stimulated IL-5 secretion. The IL-4/IL-10 and IL-4/IFN-γ ratios were higher in children with elevated total immunoglobulin E (IgE) levels. Skin prick test-negative children with eczema produced higher levels of IL-10 than skin prick test-positive children. In conclusion, atopic children have a reduced T-cell function. Atopic dermatitis is associated with increased IL-5 production, while high total IgE levels are associated with high IL-4/IFN-γ and IL-4/IL-10 ratios.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25768 (URN)10.1034/j.1399-3038.2000.00083.x (DOI)10202 (Local ID)10202 (Archive number)10202 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    3. Expression of the T-cell markers CD2 and CD28 in healthy and atopic children during the first 18 months of life
    Open this publication in new window or tab >>Expression of the T-cell markers CD2 and CD28 in healthy and atopic children during the first 18 months of life
    2003 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 14, no 3, 169-177 p.Article in journal (Refereed) Published
    Abstract [en]

    Atopy may be associated with a reduced T-cell function early in life, particularly regarding maturation of Th1 responses. The T-cell surface molecules CD2 and CD28 are involved in important T-cell activation pathways. Stimulation via the CD2 receptor increases the responsiveness to interleukin (IL)-12, which is a potent inducer of Th1 responses, whereas CD28 stimulation is critical for Th2 differentiation. Our aim was to prospectively study the expression of the cell-surface markers CD2 and CD28 on T-cells in relation to development of atopic disease. Children (n = 172) were followed from birth to 18 months and the cumulative history of atopic disease was recorded. Blood samples were obtained at birth and at 18 months, and in a subgroup of 78 infants also at 3, 6 and 12 months. Flow cytometry was used to analyze the T-cell markers CD2 and CD28, the latter also within the subsets of T-helper (CD4+) and T-cytotoxic (CD8+) cells. At 18 months, 31 children had and 118 did not have atopic symptoms. At this age, skin prick test (SPT) positive children with atopic symptoms with or without an atopic family history (AFH) showed a lower expression of CD2 mode fluorescence intensity (FI) as well as a lower proportion of CD2+ cells, as compared with non-sensitized children with neither atopic symptoms nor AFH. This was accompanied by a higher expression of CD28 FI on CD2+CD8+CD28+ cells. No significant differences were seen at time points before 18 months, although the proportion of CD2+ tended to be low also earlier in life. In conclusion, the observed reduced expression of CD2 in atopic infants may support previous findings that atopy is associated with a reduced CD2 function. The high CD28 FI in SPT positive children with atopic symptoms may possibly be a consequence of a TH2-skewed immune system.

    Keyword
    Atopic disease, CD2, CD28, Childhood, T lymphocyte
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-46607 (URN)10.1034/j.1399-3038.2003.00016.x (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13Bibliographically approved
    4. Reduced IL-2-induced IL-12 responsiveness in atopic children
    Open this publication in new window or tab >>Reduced IL-2-induced IL-12 responsiveness in atopic children
    2003 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 14, no 5, 351-357 p.Article in journal (Refereed) Published
    Abstract [en]

    Atopy may be associated with a reduced T-cell function particularly regarding maturation of T helper 1 (Th1) responses. We hypothesized that atopic children may have a reduced capacity to up-regulate the β2 subunit of the interleukin-12 (IL-12) receptor (IL-12Rβ2, the signal-transducing component). The study included 38 children followed from birth to the age of 7 years. Twenty one had a cumulative history of atopic disease, whereas 17 had none. Sixteen out of 21 children also had atopic symptoms within the past year (current), out of whom 10 children had atopic airway symptoms. The expression of IL-12Rβ2 mRNA was analyzed by quantitative real-time PCR and the secretion of interferon-γ (IFN-γ), IL-5 and IL-10 was assessed by enzyme-linked immunosorbent assay (ELISA). Children with current atopic airway symptoms and high levels of total IgE up-regulated IL-12Rβ2 mRNA expression less than non-atopic children with low IgE levels after IL-2 stimulation. This was accompanied by a low IL-2- and IL-12-induced IFN-γ production, possibly reflecting the reduced capacity of atopic children to up-regulate the IL-12 receptor. As IL-2 is needed to initiate and sustain immune responses and IL-12 promotes Th1 responses, this may contribute to the Th2-skewed pattern in atopic children.

    Keyword
    T-cells, IL-2, IL-12, IL-12Rβ2, childhood, atopic disease
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13845 (URN)10.1034/j.1399-3038.2003.00075.x (DOI)
    Available from: 2006-06-02 Created: 2006-06-02 Last updated: 2017-12-13Bibliographically approved
    5. Reduced levels of soluble CD14 in atopic children
    Open this publication in new window or tab >>Reduced levels of soluble CD14 in atopic children
    2004 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 34, no 4, 532-539 p.Article in journal (Refereed) Published
    Abstract [en]

    Background A reduced microbial stimulation has been reported as a reason for the increasing prevalence of atopic diseases in industrialized countries. Antigen-presenting cells (APC), responding to microbial signals by pattern recognition receptors such as CD14, have an important role in the development of the Th1/Th2 balance.

    Objective We hypothesized that atopic children have a lower expression of CD14 on monocytes and lower soluble CD14 levels (sCD14).

    Methods Seventy-six children were followed prospectively from birth and signs of atopic disease were evaluated. The expression of CD14 on monocytes was analysed with flow cytometry at 0, 3, 6, 12 and 18 months. Circulating levels of sCD14 were analysed by ELISA and total IgE was analysed by fluoroenzymo immunoassay at these ages, and in a subgroup, followed up at 7 years.

    Results Levels of sCD14 were reduced at 7 years both in children with a current or a cumulative history of atopy compared to non-atopic children with P=0.002 and 0.001, respectively. Sensitized children with atopic symptoms had lower sCD14 at 3 and 18 months and at 7 years of age than non-atopic non-sensitized children with P=0.023, 0.039 and 0.008, respectively.

    Conclusion The lower levels of sCD14 observed in atopic children may be a consequence of an atopic family heredity and/or atopic disease, but it may also reflect a reduced capacity to respond to microbial signals.

    Keyword
    antigen-presenting cells, atopic disease, CD14(m), childhood, Soluble CD14
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-22339 (URN)10.1111/j.1365-2222.2004.1921.x (DOI)1540 (Local ID)1540 (Archive number)1540 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
  • 4.
    Aniansson Zdolsek, Helena
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Holt, Patrick G.
    TVW Telethon Institute for Child Health Research, Perth, Australia.
    Nilsson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Expression of the T–cell markers CD3, CD4 and CD8 in healthy and atopic Children during the first 18 months of life1999In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 119, no 1, 6-12 p.Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 5. Annus, T
    et al.
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Mai, Xiaomei
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Riikjärv, MA
    Sandin, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Bråbäck, L
    Wheezing in relation to atopy and environmental factors in Estonian and Swedish schoolchildren2001In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 31, no 12, 1846-1853 p.Article in journal (Refereed)
    Abstract [en]

    Background: The prevalence of asthma and allergic diseases is significantly lower in post socialist Eastern Europe than in Western industrialized countries. The reason for this difference is largely unknown. Different types of childhood wheezing could be related to different risk factors. Objective: To compare the prevalence of respiratory symptoms, asthma and atopic diseases among Estonian and Swedish schoolchildren and to evaluate characteristics for wheezing in the two countries. Methods: In a prevalence study, population-based random samples of 10-11-year-old schoolchildren in Tallinn (n = 979), Estonia and in Link÷ping (n = 911) and ╓stersund (n = 1197), Sweden were studied by a parental questionnaire and skin prick tests (SPT). All 275 children with wheeze in the past 12 months and 710 randomly selected controls within the original cohorts were invited to a case-control study involving a parental questionnaire, examination for flexural dermatitis and bronchial challenge with hypertonic saline. The study adhered to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. Results: The prevalence of current wheezing was similar (8-10%) in the three centres, while diagnosed asthma and atopic symptoms were more common in Sweden and cold-related respiratory symptoms were more prevalent in Estonia. Frequent wheezing was more common in Sweden than in Estonia (but significantly so only in ╓stersund). Wheezing children in Sweden had a high rate of positive SPT (49% in Link÷ping and 58% in ╓stersund) bronchial hyper-responsiveness (BHR) (48% in Link÷ping and ╓stersund) and anti-asthmatic treatment (63% in Link÷ping and 81% in ╓stersund). In Estonia, the proportion of wheezing children with positive SPT, BHR and anti-asthmatic treatment was only 26%, 13% and 17%, respectively. Domestic crowding was inversely related to wheezing in one of the study areas (╓stersund). The mean baseline forced expiratory volume in one second (FEV1) was higher in Estonia than in Sweden, both in wheezing and non-wheezing children. Conclusions: Our study suggested that although wheezing symptoms were equally common in Estonia and Sweden, they were less severe in Estonia. More frequent symptoms and a high rate of atopy, BHR and anti-asthmatic medication characterized wheezing children in Sweden. In contrast, BHR, atopy and medication were uncommon among wheezing children in Estonia.

  • 6.
    Antepohl, Wolfram
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Domeij, Erica
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    A follow-up of medical graduates of a problem-based learning curriculum2003In: Medical Education, ISSN 0308-0110, E-ISSN 1365-2923, Vol. 37, no 2, 155-162 p.Article in journal (Refereed)
    Abstract [en]

    Introduction: There is little information available on the effects of problem-based undergraduate curricula on doctors and their performances after graduation. Therefore, we conducted a questionnaire study of all graduates of the new medical programme at the Faculty of Health Sciences, Link÷ping University. Methods: All 446 medical students who had graduated from the new programme were asked to fill in a questionnaire about selected activities during their studies and their careers after graduation. They were also asked to evaluate the quality of their undergraduate education retrospectively. Statistical analysis was performed using descriptive, multivariate and bivariate approaches. Results: A total of 77% of the graduates responded. They showed a high degree of overall contentment with their undergraduate education and felt well prepared for professional life during their preregistration period and specialist education (mean = 4.0 on a 6-point Likert scale ranging from 0 to 5). They felt especially well prepared in terms of skills for communication with patients, collaboration with other health professionals and development of critical thinking/scientific attitudes. The students' age at the beginning of their studies correlated positively with their contentment as graduates, especially in terms of preparation for patient communication and collaboration with other health professionals. No differences between students originally admitted via a local admission procedure and those admitted via a national procedure were detected concerning retrospective evaluation of undergraduate medical education. Conclusion: Graduates of the new curriculum showed a high degree of satisfaction with their undergraduate education and its preparation of them for medical practice. Specifically, they were very content with the particular emphases of the new curriculum.

  • 7. Arbring, K
    et al.
    Nelson, Nina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Cortisol response to heelstick stressor in preterm infants2000In: Prenatal and Neonatal Medicine, ISSN 1359-8635, E-ISSN 1473-0774, Vol. 5, no 3, 182-185 p.Article in journal (Refereed)
    Abstract [en]

    To evaluate the hormonal response to stress in healthy preterm infants, we measured concentrations of serum cortisol at baseline and after capillary heelstick. Eleven preterm infants, five girls and six boys, with gestational ages ranging from 30 to 34 weeks, were studied. We measured the serum cortisol concentration before and 30 min after capillary heelstick on days 1, 3 and 7 of life. On days 3 and 7, but not on day 1, the rise in cortisol was significant (p = 0.02 and 0.04, respectively). The reduced response on day 1 can probably be explained by the significantly higher baseline concentrations. We suggest that a test like this can be useful in evaluating the hormonal stress response in preterm as well as full-term infants.

  • 8.
    Axelsson, Stina
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Hjorth, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Åkerman, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Casas, Rosaura
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Early induction of GAD(65)-reactive Th2 response in type 1 diabetic children treated with alum-formulated GAD(65)2010In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 26, no 7, 559-568 p.Article in journal (Refereed)
    Abstract [en]

    Background We have previously shown that two injections of 20 mu g alum-formulated glutamic acid decarboxylase 65 (GAD(65)) (GAD-alum; Diamyd (R)) in children with recent-onset type 1 diabetes lead to preservation of residual insulin secretion. In vitro cytokine production at the 15 months follow-up indicated immunomodulation. In the present study, we took advantage of peripheral blood mononuclear cells, cryopreserved during early follow-ups, to investigate whether the immunomodulatory effect of GAD-alum was apparent earlier after treatment, preceding the changes previously reported at 15 months.<p>Methods Peripheral blood mononuclear cells from 70 type 1 diabetic children, randomly assigned GAD-alum (n = 35) or placebo (n = 35), that had been frozen at baseline (n = 27) and after 1 (n = 58), 3 (n = 67) and 9 (n = 66) months, were stimulated in vitro with GAD(65), tyrosine phosphatase-like protein IA-2 peptide, insulin peptide, GAD-alum, alum formulation or phytohaemagglutinin. Interleukin (IL)-5, -6, -10, -12, -13, -17, tumour necrosis factor and interferon-gamma were measured in cell supernatants and serum samples using Luminex. Expression of FOXP3 and transforming growth factor-beta was determined by real-time reverse transcription polymerase chain reaction.</p><p>Results Already 1 month after the first injection, GAD(65)-induced IL-5 and IL-13 together with FOXP3 were enhanced in GAD-alum-treated patients compared to those with placebo. The in vitro response at 3 and 9 months was characterized by a broader range of cytokines in the treated group. Notably, only the T-helper 2-associated cytokines IL-5 and IL-13 together with FOXP3 increased continuously over time.</p><p>Conclusions Treatment with GAD-alum in type 1 diabetic children induced an early T-helper 2 immune enhanced response to GAD(65), followed by a wider spectrum of cytokines at 3 and 9 months. Copyright (C) 2010 John Wiley &amp; Sons, Ltd.</p>

  • 9.
    Benn, CS
    et al.
    Dept of Epidemiology Köpenhamn, Danmark.
    Fagerås Böttcher, Malin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Pedersen, BV
    Dept of Epidemiology Köpenhamn, Danmark.
    Filteau, SM
    Centre of International Child Health London, UK.
    Duchén, Karel
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Mammary epithelial paracellular permeability in atopic and non-atopic mothers versus childhood atopy2004In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 15, no 2, 123-126 p.Article in journal (Refereed)
    Abstract [en]

    Sodium/potassium (Na/K) ratios are considered to be a marker of mammary epithelial paracellular permeability. The aim of the present study was to investigate the association between maternal atopy and Na/K ratios in breast milk and the association between Na/K ratios in breast milk and the development of atopy in the offspring. Early and mature milk samples were obtained from 30 atopic and 43 non-atopic women. We found no differences in the Na/K ratios between atopic and non-atopic women. At 18 months of age, 22 (30%) of the children had a positive skin prick test (SPT) and 26 (36%) had symptoms of atopic diseases. Overall, high levels of Na/K compared with low and slightly raised levels of Na/K in the maternal milk tended to be associated with a positive SPT and atopic disease. However, if the mother was atopic, high levels of Na/K in early or mature milk were associated with a significantly increased risk of a positive SPT or atopic disease in the offspring [RR = 4.8 (1.9-12)] whereas no such association was observed in non-atopic mothers [RR = 0.8 (0.4-1.7), p for interaction = 0.001]. Thus, high Na/K levels in the breast milk may be associated with the development of atopy and atopic diseases in the offspring of atopic mothers.

  • 10. Berg, I
    et al.
    Finnström, Orvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Nygren, KG
    Barn födda efter in vitro-fertilisering i Sverige 1982-19972001In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 98, 4020-4025 p.Article in journal (Other academic)
  • 11.
    Berzina, L.
    et al.
    Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Saduaskaite-Kühne, Vaiva
    Laboratory of Pediatric Endocrinology, Kaunas University of Medicine, Kaunas, Lithuania.
    Nelson, Nina
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Shtauvere-Brameus, A.
    Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
    Sanjeevi, C. B.
    Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
    DR3 is associated with type 1 diabetes and blood group ABO incompatibility2002In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 958, 345-348 p.Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes is associated with autoimmunity against pancreatic β cells. ABO incompatibility is associated with ABO immunization during pregnancy. Type 1 diabetes is associated with certain HLA DR and DQ haplotypes. The mechanism by which blood group incompatibility is associated with the risk of type 1 diabetes is not known. We propose that certain HLA alleles contribute to the development of both type 1 diabetes and ABO blood group incompatibility. We studied 57 children with ABO blood group incompatibility, 118 children with type 1 diabetes, and 98 age- and sex-matched unrelated healthy controls from Linköping. Typing of HLA DQA1, DQB1, and DRB1 was done on DNA extracted from peripheral blood, by PCR amplification, manual dot-blotting onto nylon membranes, synthetic sequence-specific oligonucleotide (SSO) probe 3′ end-labeling with 32P-dCTP, and hybridization followed by stringency washes and autoradiography. We observed that DR3 allele was more frequent in patients with ABO incompatibility when compared to healthy controls (OR = 2.7, Pc < 0.05). Patients with type 1 diabetes had significantly higher frequency of DR3, DQ2, DR4, and DQ8 alleles when compared to healthy controls. No significant difference was observed in frequency of DR3 between ABO blood group incompatibility and type 1 diabetes patients. We conclude that DR3 is associated with both the development of type 1 diabetes and ABO incompatibility.

  • 12. Berzina, L
    et al.
    Shtauvere-Brameus, S
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Sanjeevi, CB
    Newborn screening for high-risk human leukocyte antigen markers associated with insulin-dependent diabetes mellitus: The ABIS study2002In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 958, 312-316 p.Article in journal (Refereed)
    Abstract [en]

    Type 1 (insulin-dependent) diabetes mellitus is associated with specific high-risk HLA DQ and DR haplotypes and islet cell antibodies. IDDM susceptibility in Caucasians is more strongly associated with DQ2/DQ8 (DQA1*0501-DQB1*0201/DQA1*0301-DQB1*0302) and DQ6 (B1*0604) than with DRB1*03/DRB1*04, while a single copy of DQ6 (B1*0602) gives sufficient protection against type 1 diabetes. As a part of the ABIS (All Babies in Southeast Sweden) study we have done typing of DQA1, DQB1, and DRB1 by polymerase chain reaction (PCR) amplification of the second exon of the genes, manually dot-blotting onto nylon membranes synthetic sequence-specific oligonucleotide (SSO) probes, 3' end-labeling with 32P-dCTP, and hybridization followed by stringency washes and autoradiography using the SSO probe. Among 3756 newborns born in southeast Sweden we have found the high-risk genotype DQ2/DR3-DO8/DR4 to be present in 1%, haplotype DQ8/DR4 in 7.8%, and haplotype DQ2/DR3 in 9.6%. DQ2/DR3 or DQ8/DR4 was carried by 16.4% of newborns, the low-risk DQ6 molecule was carried by newborns as follows: DQ2/DR3-DQ6/DR15, 1.3%, DQ8/DR4-DQ6/DR15, 1.3%, and DQ6/DR15, 9.4%. We conclude from our results that the high incidence of IDDM in Sweden is at least in part due to increased prevalence of high-risk HLA haplotypes compared to protective haplotypes (20% vs. 13%) in the general population.

  • 13. Bevan, S
    et al.
    Popat, S
    Braegger, CP
    Busch, A
    O'Donoghue, D
    Fälth-Magnusson, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Ferguson, A
    Godkin, A
    Hogberg, L
    Holmes, G
    Hosie, KB
    Howdle, PD
    Jenkins, H
    Jewell, D
    Johnston, S
    Kennedy, NP
    Kerr, G
    Kumar, P
    Logan, RFA
    Love, AHG
    Marsh, M
    Mulder, CJJ
    Sjöberg, K
    Stenhammar, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Walker-Smith, J
    Marossy, AM
    Houlston, RS
    Contribution of the MHC region to the familial risk of coeliac disease. 1999In: Journal of Medical Genetics, ISSN 0022-2593, E-ISSN 1468-6244, Vol. 36, 687-690 p.Article in journal (Refereed)
  • 14.
    Björkqvist, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Coagulase-negative staphylococci septicaemia in newborns: aspects on host-bacterial interactions with special regard to neutrophil and endothelial response2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Newborn infants, especially those born preterm, are immunologically immature and prone to invasive infections. As a result of the increasing survival of very preterm (VPT < 31 weeks gestational age) newborns, nosocomial septicaemia has become a major concern the neonatal intensive care, and coagulase-negative staphylococci (CoNS) are nowadays the most frequently isolated pathogens in neonatal blood cultures. Further insight into host-bacterial interactions is required for the development of preventive strategies against CoNS septicaemia in VPT newborns.

    Aim of the study: To investigate host-bacterial interactions in neonatal CoNS septicaemia with special regard to the neutrophil and endothelial response and to bacterial virulence factors.

    Methods and results: Neonatal blood isolates of CoNS collected at Örebro University Hospital, Örebro, Sweden during the years 1983-1997 were characterised clinically and according to species and to phenotypic and genotypic patterns. Biochemial fingerprinting was found useful as a screening tool for selection of phenotypically related strains, but for further discrimination within a phenotypic cluster, genetic fingerprinting by pulsed field gel electrophoresis (PFGE) was required.

    The isolates of S. epidermidis collected during the later part of the study period (1990-1997, n = 50) were further investigated. A hypervirulent clone of bacteria was identified, representing 7 of the 12 sepsis isolates in that cohort. These 12 isolates of S. epidermidis induced significantly higher endothelial release of neutrophil chemoattractants from human umbilical vein endothelial cell (HUVEC) cultures than did the isolates regarded as skin contaminants (n = 38). There were no differences between the sepsis and contaminant groups in the prevalence of genes for biofilm production, methicillin resistance or fibrinogen-binding protein.

    The neutrophil oxidative burst occuring after stimulation by different bacterial strains was investigated by a flow cytometric method applied to a whole blood model. The oxidative activity in unstimulated neutrophils was similar in term (n = 10) and preterm (n = 10) newborns. However, the term newborns showed a significantly higher capacity to up-regulate the oxidative burst after bacterial stimulation. Significant differences in oxidative responses to different bacterial strains were observed, but these differences could not be related exclusively to species or invasive capacity.

    A neutrophil granule protein, human neutrophil lipocalin (HNL), was evaluated as an early marker of neonatal septicaemia in newborns with clinical signs of infection. The serum level of HNL was significantly higher in the infected group of neonates (n = 25) than in the group with non-proven infection (n = 62). In healthy term controls the HNL level was similar at age 3 days to that at birth and close to the level reported in healthy adults.

    Conclusions: The increased up-regulation of endothelial inflammatory mediators induced by sepsis isolates of S. epidermidis represents an important step in the pathogenesis of neonatal CoNS septicaemia. HNL might be useful as a marker of neutrophil activity also in VPT newborns. The laboratory assays used in the present study can be further developed for future investigations of the pathogenesis and host-bacterial interactions in neonatal CoNS septicaemia.

    List of papers
    1. Phenotypic and genotypic characterisation of blood isolates of coagulase-negative staphylococci in the newborn
    Open this publication in new window or tab >>Phenotypic and genotypic characterisation of blood isolates of coagulase-negative staphylococci in the newborn
    Show others...
    2002 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 110, no 4, 332-339 p.Article in journal (Refereed) Published
    Abstract [en]

    Coagulase-negative staphylococci (CNS) are the leading cause of late-onset sepsis in newborns (>72 h of age). Our aim was to determine whether phenotypic and/or genotypic differences existed between blood isolates of CNS regarded as inducers of sepsis or as contaminants. Ninety-seven bloodisolates of CNS recovered from newborns at the neonatal intensive care unit, Örebro, Sweden in 1983–1997 were analysed. Twenty-nine of them (30%) were classified as sepsis isolates and 68 (70%) as contaminants. The most prevalent species was Staphylococcus epidermidis (n=59). Staphylococcus haemolyticus (n=16) was most often isolated from newborns with the lowest gestational age and birth weight. Biochemical typing using the Phene Plate system (PhP) and genotyping using pulsed-field gel electrophoresis (PFGE) showed that the S. epidermidis isolates regarded as inducers of sepsis (n=16) were more homogeneous than isolates considered contaminants (n=37). One main genotypic group, representing seven (44%) isolates, was identified among the sepsis isolates. Phenotypically the S. epidermidis sepsis isolates comprised three major clusters. In contrast, among the S. epidermidis contaminants, eight genotypic groups and two phenotypic clusters were identified. The dominating genotypic group among the sepsis isolates of S. epidermidis may represent strains with higher invasive capacity.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-85065 (URN)10.1034/j.1600-0463.2002.100408.x (DOI)
    Available from: 2012-11-01 Created: 2012-11-01 Last updated: 2017-12-07
    2. Human neutrophil lipocalin: normal levels and use as a marker for invasive infection in the newborn
    Open this publication in new window or tab >>Human neutrophil lipocalin: normal levels and use as a marker for invasive infection in the newborn
    Show others...
    2004 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 93, no 4, 534-539 p.Article in journal (Refereed) Published
    Abstract [en]

    Aim: To evaluate human neutrophil lipocalin (HNL) as a marker of neonatal invasive infection and determine the normal serum levels of HNL in newborns.

    Methods: HNL is released from neutrophil granulocytes and is regarded as a specific marker of neutrophil activity. In 81 newborns 28 d of age with signs of infection on a total of 87 occasions, HNL and C-reactive protein (CRP) were measured at inclusion and on the three following days. As controls, term healthy newborns were recruited at birth (cord blood, n= 45) and at ages 3-5 d (n= 46). Serum HNL was measured by a radioimmunoassay.

    Results: 25/87 episodes were classified as infection and 62 as non-proven infection. HNLmax was significantly higher in the infected group (mean 587.6 μg/1) than in the non-proven infected group (mean 217.7 μg/1, p > 0.001). HNL peaked at inclusion, 1 d earlier than CRP. In the healthy controls, HNL was the same at 3-5 d of age as at birth (mean 82.4-81.7 μg/1) and similar to normal adult levels.

    Conclusions: The release of HNL is not increased in healthy newborns at birth, but neonatal neutrophils rapidly release HNL upon microbial stimulation in vivo. HNL might be useful as an early marker of neonatal infection.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-85066 (URN)10.1080/08035250410024754 (DOI)
    Available from: 2012-11-01 Created: 2012-11-01 Last updated: 2017-12-07
    3. Defective neutrophil oxidative burst in preterm newborns on exposure to coagulase-negative staphylococci
    Open this publication in new window or tab >>Defective neutrophil oxidative burst in preterm newborns on exposure to coagulase-negative staphylococci
    Show others...
    2004 (English)In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 55, no 6, 966-971 p.Article in journal (Refereed) Published
    Abstract [en]

    The neutrophil oxidative burst is a product of the regulated assembly of the multicomponent oxidase enzyme. Our aim was to compare the oxidative burst in term (n = 10) and preterm newborns <31 wk gestational age (n = 10) after stimulation with coagulase-negative staphylococci in vitro. Strains of Streptococcus epidermidis with different invasive and slime-producing properties, one strain of S. haemolyticus, and one strain of group B-streptococcus were investigated. A whole-blood flow cytometric assay using the oxidation of hydroethidine to ethidium bromide was used. The oxidative activity in unstimulated neutrophil granulocytes [polymorphonuclear leukocytes (PMNLs)] was similar in term and preterm newborns, but the preterm newborns showed a significantly lower capacity to up-regulate the oxidative burst intensity after bacterial stimulation (p = 0.004). In the term but not in the preterm group, the oxidative burst intensity after bacterial stimulation correlated with the baseline oxidative burst intensity. After bacterial stimulation, there was a trend toward a greater percentage of activated neutrophils in the term group than in the preterm group, but the difference was less pronounced than that in oxidative burst intensity. Significant differences in oxidative burst response to different bacterial strains were observed (p < 0.001), but the differences could not be correlated exclusively to invasive capacity or slime-producing properties. It is concluded that the baseline oxidative activity is similar in term and preterm PMNLs but that preterm PMNLs have a decreased capacity to increase the oxidative burst in response to bacterial stimulation.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-85067 (URN)10.1203/01.pdr.0000127018.44938.89 (DOI)
    Available from: 2012-11-01 Created: 2012-11-01 Last updated: 2017-12-07
    4. Increased endothelial activation in neonatal sepsis isolates of Staphylococcus epidermidis, but no differences in biofilm producing properties between sepsis and contaminant isolates
    Open this publication in new window or tab >>Increased endothelial activation in neonatal sepsis isolates of Staphylococcus epidermidis, but no differences in biofilm producing properties between sepsis and contaminant isolates
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Staphylococcus epidermidis is the predominating etiological agent in neonatal septicemia today, but specific specific factors associated with S. epidermidis are incompletely described. We compared neonatal blood isolates of S. epidermidis representing sepsis (n = 12) or skin contaminants (n = 38) regarding endothelial activation, and the prevalence of genes encoding for biofilm production (icaAB and D), fibrinogen-binding protein (fbe) and methicillin resistance (mecA).

    Endothelial cells cultured from human umbilical veins (HUVEC) were challenged by the different isolates of S. epidermidis. Endothelial release of adhesion molecules and interleukin-8 (IL-8) was investigated by an ELISA. Endothelial cell death was determined by light microscopy. The different genes were detected by PCR, and phenotypic biofilm production was investigated by Trypan blue staining. The sepsis isolates of S. epidermidis induced significantly higher endothelial release of intracellular adhesion molecule 1 (ICAM-1, p = 0.0021), endothelial selectin (E-selectin, p = 0.002), and IL-8 (p = 0.010) compared to the contaminants. Vaseular cell adhesion molecules 1 (VCAM-1) was not released. The sepsis-isolates were more cytotoxic than the contaminants; Nine out of 12 sepsis strains induced ≥ 50% cytotoxicity to HUVEC, compared to 15/38 contaminant strains (p = 0.047). The prevalence of the ica-operon, biofilm-production, fbe-, or mecA genes did not discriminate between sepsis and contaminant isolates. It is concluded that sepsis isolates of S. epidermidis induced higher endothelial release of chemotactic inflammatory mediators compared to contaminant isolates, but that the production of biofilm might be less important in neonatal infections eaused by S. epidermidis.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-85068 (URN)
    Available from: 2012-11-01 Created: 2012-11-01 Last updated: 2012-11-01
  • 15.
    Björkstén, B
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Allergy priming early in life. 1999In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 353, 167-168 p.Article in journal (Refereed)
  • 16.
    Björkstén, B
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Environment and infant immunity. 1999In: Proceedings of the Nutrition Society, ISSN 0029-6651, E-ISSN 1475-2719, Vol. 58, 729-732 p.Article in journal (Refereed)
  • 17.
    Björkstén, B
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Food and asthma2000In: Practical Issues in Asthma Management, ISSN 1388-7319, Vol. 14Article in journal (Refereed)
  • 18.
    Björkstén, B
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Perinatal events in relation to sensitization in the human2000In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 162, no 3 IIArticle in journal (Refereed)
  • 19.
    Björkstén, B
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    The environmental influence on childhood asthma. 1999In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 54, 17-23 p.Article in journal (Refereed)
  • 20.
    Björkstén, B
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Unmet needs in the treatment of asthmatic children and adolescents.2000In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 30Article in journal (Refereed)
  • 21.
    Björkstén, B
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Naaber, P
    Sepp, E
    Mikelsaar, M
    The intestinal microflora in allergic Estonian and Swedish 2-year-old children. 1999In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 29, 342-346 p.Article in journal (Refereed)
  • 22.
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Primary prevention of atopic asthma.2001In: Current Opinion in Allergy and Clinical Immunology, ISSN 1528-4050, E-ISSN 1473-6322, Vol. 1, 545-548 p.Article in journal (Refereed)
  • 23.
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    The epidemiology of food allergy2001In: Current Opinion in Allergy and Clinical Immunology, ISSN 1528-4050, E-ISSN 1473-6322, Vol. 1, 225-227 p.Article in journal (Refereed)
  • 24.
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    The gastrointestinal flora and the skin. Is there a link?2001In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, 51-56 p.Article in journal (Refereed)
  • 25. Blomqvist, M
    et al.
    Juhela, S
    Erkkila, S
    Korhonen, S
    Simell, T
    Kupila, A
    Vaarala, Outi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Simell, O
    Knip, M
    Ilonen, J
    Rotavirus infections and development of diabetes-associated autoantibodies during the first 2 years of life.2002In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 128, 511-515 p.Article in journal (Refereed)
  • 26. Bohmova, K
    et al.
    Hladikova, Z
    Cerny, M
    Flajsmanova, K
    Vrabelova, Z
    Skramlikova, T
    Spalova, I
    Cerna, M
    Chudoba, D
    Pithova, P
    Stadlerova, G
    Bartaskova, D
    Faresjö, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Stechova, K
    Cord blood cytokine profile detection in neonates with T1D parents - Monitoring of cellular auto-reactivity using protein microarray2007In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 66, no 5, 563-571 p.Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes (T1D) is a great medical challenge and its incidence rises rapidly. T lymphocytes and their cytokine production are supposed to play a major role in T1D development. So far, there is no potent tool to recognize the early signs of cellular auto-reactivity which leads to β-cell damage. The naïve immune system of the newborn (not yet influenced by external factors) can be used as an important model for T1D pathogenesis studies. Cord blood samples of 22 healthy neonates born at term to a diabetic parent (T1DR) and 15 newborns with no family history of any autoimmune disease (controls) were collected. Determination of 23 cytokines was performed before and after the stimulation with diabetogenic autoantigens using protein microarray. We observed lower basal production of all detected cytokines in the T1DR group - granulocyte/macrophage colony-stimulating factor (GM-CSF) (P = 0.025), growth regulated protein (GRO) (P = 0.002), GRO-α (P = 0.027), interleukin (IL)-1-α (P = 0.051), IL-3 (P = 0.008), IL-7 (P = 0.027), IL-8 (P = 0.042), monocyte chemoattractant proteins (MCP)-3 (P = 0.022), monokine-induced by IFN-γ (MIG) (P = 0.034) and regulated upon activation normal T-cell express sequence (RANTES) (P = 0.004). Exclusively lower post-stimulative levels of G-CSF (P = 0.030) and GRO-α (P = 0.04) were observed in controls in comparison with the basal levels. A significant post-stimulative decrease in G-CSF (P = 0.030) and MCP-2 (P = 0.009) levels was observed in controls in comparison with T1DR neonates. We also observed the interesting impact of the risky genotype on the protein microarray results. Protein microarray seems to be a useful tool to characterize a risk pattern of the immune response for T1D also in newborns. © 2007 The Authors.

  • 27. Bojestig, M
    et al.
    Nyström, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Karlberg, Bengt E
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    The renin-angiotensin-aldosterone system is suppressed in adults with Type 1 diabetes2000In: jraas. Journal of the renin-angiotensin-aldosterone system, ISSN 1470-3203, E-ISSN 1752-8976, Vol. 1, no 4, 353-356 p.Article in journal (Refereed)
    Abstract [en]

    Poor glycaemic control and high blood pressure are two important risk factors for the development of retinopathy and nephropathy in Type 1 diabetes. The renin-angiotensin-aldosterone system (RAAS) may be involved in this process, since treatment with angiotensin-converting enzyme (ACE) inhibitors postpones the development of these complications. We investigated whether plasma renin activity (PRA), plasma angiotensin II (Ang II) and atrial natriuretic peptide (ANP) differed in Type 1 diabetic patients compared with healthy controls. We recruited 80 patients with Type 1 diabetes of more than 10 years' duration and 75 age-matched controls. We found that PRA and Ang II concentrations were significantly lower in patients than in the controls. The levels of ANP, on the other hand, were higher in patients than in controls. PRA correlated negatively to the mean value of HbA1c during the previous five years. PRA and Ang II were significantly lower in patients with mean HbA1c. >8.4% compared with those with mean HbA1c 7.2%. In summary, we found patients with Type 1 diabetes to have RAAS suppression and increased ANP levels, suggesting a state of fluid retention.

  • 28.
    Boman, Krister
    et al.
    Barncancerforskningsenheten Karolinska sjukhuset, Stockholm.
    Viksten, Jonas
    Avd för Psykologi Stockholms Universitet.
    Kogner, Per
    Barncancerforskningsenheten Karolinska sjukhuset, Stockholm.
    Samuelsson, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Serious illness in childhood: the different threats of cancer and diabetes from a parent perspective.2004In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 145, 373-379 p.Article in journal (Refereed)
    Abstract [en]

    Objectives To compare the incidence of disease-related distress symptoms in parents of children with cancer and diabetes. Study design A total of 675 parents of patients with cancer, patients with diabetes, and control subjects were assessed for 11 distress symptom clusters. Patient and control parent mean differences were tested by 2-tailed t tests, illness groups were compared by means of analysis of variance. Distress variations as a function of time since diagnosis were examined by regression analysis. Results The distress levels of patient parents exceeded those of control parents for global distress (P < .0001) and for most symptom subcategories. Distress levels of parents of patients with cancer (CP) significantly exceeded those of parents of patients with diabetes (DP) in anxiety (P < .0001), physical and psychologic distress (P < .0001), depression (P < .005), and loneliness (P < .05). Levels in DP matched those of CP in uncertainty, loss of control/the patient, self-esteem, disease-related fear, and sleep disturbances. Distress levels were lower in CP most distant hi time from diagnosis, whereas DP showed a reversed trend. Conclusions Parental distress patterns in childhood illness depend on illness type and time passed since diagnosis. Symptom profiles verify the need for psyehosocial attention at the initial shock after the cancer diagnosis and indicate long-term consequences for many parents. In pediatric diabetes, the persistence or intensification of distress over time is of specific clinical relevance.

  • 29. Brekke, Hilde
    et al.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Vitamin D supplementation and diabetes-related autoimmunity in the ABIS study2007In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 8, no 1, 11-14 p.Article in journal (Refereed)
    Abstract [en]

    Supplementation with vitamin D during infancy, as well as intake of vitamin D during pregnancy, has been associated with decreased risk of type 1 diabetes or diabetes-related autoantibodies in children. The primary aim of this report was to investigate whether vitamin D supplementation during infancy is associated with diabetes-related autoimmunity at 1 and 2.5 yr in the children. Second, we examined whether consumption of vitamin-D-containing supplements during pregnancy is related to risk of autoimmunity in the offspring. Screening questionnaires were completed for 16 070 infants after delivery, including a food-frequency questionnaire regarding the mother's use of dietary supplements during pregnancy. Parents of 11 081 and 8805 infants completed a follow-up questionnaire regarding the use of vitamin supplementation at 1 and 2.5 yr, respectively. Autoantibodies against glutamic acid decarboxylase and islet antigen-2 (IA-2) were analyzed in whole blood from 8694 children at 1 yr and 7766 children at 2.5 yr. Supplementation with AD-drops was not associated with autoantibodies at 1 or 2.5 yr. Use of vitamin-D-containing supplements during pregnancy was associated with reduced diabetes-related autoimmunity at 1 yr (adjusted odds ratio: 0.707, confidence interval: 0.520-0.962, p = 0.028) but not at 2.5 yr. In conclusion, no association was found between an intermediate dose of vitamin D supplementation during infancy and development of diabetes-related autoantibodies at 1 and 2.5 yr. Use of vitamin-D-containing supplements during pregnancy was associated with reduced development.

  • 30.
    Brekke, Hilde
    et al.
    Avd för klin nutrition, Sahlgrenska sjukhuset.
    Ludvigsson, Jonas
    Barnkliniken, Örebro.
    van Odijk, J
    Avd för klin nutrition Sahlgrenska sjukhuset.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Breastfeeding and introduction of solid foods in Swedish infants; the All Babies in Southeast Sweden study2005In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 94, no 3, 377-382 p.Article in journal (Refereed)
    Abstract [en]

    The aim of this report is to describe breastfeeding duration and introduction of foods in Swedish infants born 1997-9, in relation to current recommendations. A secondary aim is to examine breastfeeding duration and introduction of certain allergenic foods in allergy-risk families (for whom allergy-preventive advice has been issued). Out of 21 700 invited infants, screening questionnaires were completed for 16 070 infants after delivery. Parents to 11 081 infants completed a follow-up questionnaire regarding breastfeeding and introduction of foods and 9849 handed in detailed food diaries at 1 year of age. The percentages of infants who were exclusively breast-fed at 3, 6 and =9 months of age were 78.4, 10.1 and 3.9, respectively. The corresponding percentages for partial breastfeeding were 87.8, 68.9 and 43.6. Gluten-containing foods were introduced to 66 % of infants between 4 and 6 months, as recommended at the time of the study, and one-quarter had stopped breastfeeding when gluten was introduced. More than 90 % of parents introduced the first sample of solid food during months 4-6, as recommended. Fish and eggs had been introduced during the first year in 43 % and 29 %, respectively, of infants with atopic heredity. Exclusive breastfeeding duration and time of introduction of solid foods, including gluten, seemed to have been in line with Swedish recommendations at the time, although gluten was often introduced late, and not during ongoing breastfeeding as recommended. The adherence to allergy-preventive advice was less than optimal in infants with atopic heredity.

  • 31.
    Brekke, Hilde
    et al.
    Göteborgs Universitet.
    van Odijk, Jenny
    Göteborgs Universitet.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Predictors and dietary consequences of frequent intake of high-sugar, low-nutrient foods in 1-year-old children participating in the ABIS study2007In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 97, no 1, 176-181 p.Article in journal (Refereed)
    Abstract [en]

    Foods rich in sugar have been suggested to contribute to the increasing prevalence of obesity in children. The aim of this report is to investigate the dietary pattern in 1-year-old children who frequently receive foods rich in sugar but low in nutrients and to study associated demographic and parental factors. During 1977-9, 21 700 infants were invited to participate in this prospective, population-based, longitudinal cohort study. Screening questionnaires were completed for 16 070 infants after delivery. Follow-up questionnaires from 10 762 children at 1 year of age are included in the analysis. It was found that 24% of the children received sweets/pastries more often than one or two times per week. They had a higher intake of French fries, potato crisps and cream as well as a lower intake of fruit and vegetables. A frequent intake of sugar-rich, low-nutrient foods was significantly associated with several maternal factors (high intake of sweets/pastries during pregnancy, young age, mother living alone) as well as presence of older siblings. Maternal smoking during pregnancy and maternal overweight were of borderline significance. Parental education level was inversely associated with the frequency of intake of sweets/pastries in the child. Children who frequently receive sweets/pastries also have an otherwise unfavourable dietary pattern. Several parental and demographic factors were associated with this feeding pattern, especially high intake of sweets/pastries during pregnancy. Screening of pregnant women for risk predictors like consumption of sweets/pastries, young age and smoking could be possible ways of identifying children at future risk for low dietary quality.

  • 32. Brorson, L-O
    et al.
    Nyman, E
    pettersson, L-E
    Schollin, J
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Barn som kräver särskilt stöd får hjälp av olika kompetenser. Pedagoger, psykologer, socialarbetare och medicinare samverkar i Örebro.1999In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 96, 4934-4934 p.Article in journal (Other (popular science, discussion, etc.))
  • 33. Bråbäck, L
    et al.
    Plaschke, P
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Boman, G
    Jansson, C
    Stora geografiska skillnader i förekomst av astma och allergi. Internationella befolkningsstudier har sökt sambandsfaktorer2001In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 98, 5322-5326 p.Article in journal (Other academic)
  • 34.
    Bråbäck, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Respiratory symptoms and atopic sensitization among school children in different settings around the Baltic Sea1995Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this thesis was to assess the prevalence of respiratory symptoms and atopic sensitization and related risk faCtors amo:Og school children in urban and rural areas of Sundsvall in Northern Sweden and urban areas of Konin in Poland and Tallinn and Tartu in Estonia. Ambient levels of N02 were similar in urban Sundsvall and Konin whereas levels of S02 and smoke were about 5 times higher in Konin than in Sundsvall. Children in Estonia and Poland had a lower standard of living and were more exposed to indoor air pollutants.

    Among 10 527 school children in Sundsvall aged 7-16 years the prevalence of asthma was 4% in 1985. No differences were seen between urban and rural Sundsvall. School absenteeism due to asthma was uncommon.

    The prevalence of positive skin prick tests in 642 school children (aged 10, 12 and 14 years) from urban and rural areas of Sundsvall was detem1ined in 1988. In this study, urban living was a risk factor for at least one positive skin prick test to pollen or animal dander, OR 1.83(95% Cl 1.26- 2.67). The increased risk was only demonstrated among children with atopic heredity. Passive monitoring of nitrogen dioxide in Sundsvall showed that urban children as compared with rural children were exposed to higher levels of NC>z (13 ;tglm3 and 7 ;tglm3, respectively). The children spent 90% of their time indoors. The most important source of exposure were the indoor skating arenas, where levels up to 8()(X) ;tglm3 were measured during 1-hour periods.

    Parental questionnaires, skin prick tests and serial peak flow measurements for a period of 2 weeks were used in the next study involving 2594 10-12 year old children from Sweden, Poland and Estonia. Respiratory symptoms were common whereas positive skin prick tests were uncommon in Poland and Estonia. The risk for positive skin prick test was decreased in Konin, OR 0.58 (95% CI 0.37- 0.91) but increased in urban Sundsvall, 1.67 (95% Cl 1.15- 2.42) (rural Sundsvall reference group). The odds ratios in Estonia were similar to Poland. Current maternal smoking had a strong dose-resp.:mse association with current coughing attacks but only in Eastern Europe. An inverse relationship was recorded between domestic crowding and sensitization, the risk of scnsitization increased as the number of persons in the household decreased (OR 0.58, 95% Cl 0.43- 0.77).

    The study suggests that factors related to domestic crowding protect against atopic sensitization in Estonia and Poland. In Sweden, by contrast, an increased standard of living with less crowding and less infections is associated with enhanced vulnerability to air pollutants andother adjuvant factors.

  • 35. Bråbäck, Lennart
    et al.
    Kjellman, N-I.Max
    Sandin, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Atopy among schoolchildren in northern and southern Sweden in relation to pet ownership and early life events2001In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, no 1Article in journal (Refereed)
    Abstract [en]

    Studies have suggested a higher prevalence of asthma and allergies in northern, as compared to southern. Scandinavia. The aim of this study was to evaluate regional differences in atopy in relation to pet ownership and certain early life events among schoolchildren. (n=2108) aged 10-11 years from Link÷ping in southern Sweden and ╓stersund in northern Sweden. The parents completed a questionnaire, comprising questions on home environment, heredity, socio-economic conditions, and the core questions on symptoms from the International Study of Asthma and Allergies in Childhood. The children were skin-prick tested to eight common inhalant allergens. Information on maternal smoking habits, gestational age, and anthropometric measures were obtained from the Swedish Medical Birth Registry. The prevalence of atopic symptoms and sensitization to pollen were similar in ╓stersund and in Link÷ping. A higher prevalence of sensitization to animal dander among children in ╓stersund could be linked to a higher occurrence of pets in the community. Current cat ownership was related to less sensitivity to cat allergen but only in children with an atopic heredity. Ponderal index >30 kg/m3 was related to an increased risk of atopic sensitization, both in Link÷ping (adjusted odds ratio 2.1, 95% confidence interval 1.1-4.0) and in ╓stersund (adjusted odds ratio 2.0, 95% confidence interval 1.1-3.5). Maternal smoking during pregnancy was related to an increased risk of atopic sensitization among children in Link÷ping, whereas current smoking was associated with a decreased risk of sensitization in -stersund. In conclusion, we demonstrated that a high occurrence of pets in the community was associated with sensitization, whereas atopic symptoms were essentially unaffected. This study has also suggested an association between body size at birth and atopic sensitization at 10-11 years of age.

  • 36.
    Böttcher, Malin
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Bjurström, Jenny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Mai, Xiaomei
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Allergen-induced cytokine secretion in atopic and non-atopic asthmatic children2003In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 14, no 5, 345-350 p.Article in journal (Refereed)
    Abstract [en]

    Atopic asthma is characterized by excessive T helper 2 (Th2)-like immunity to allergens in the bronchial mucosa. The Th2-cytokine interleukin (IL)-4 induces IgE production, while the Th2-cytokine IL-5 promotes eosinophilic inflammation in the airways of asthmatics. Most asthmatics are atopic, but a subgroup is non-atopic. We hypothesize that allergen-induced Th2, particularly IL-5, responses can be observed in peripheral blood in both atopic and non-atopic asthmatic children but not in healthy control children. The aim of the present study was to determine IL-4, IL-5, IL-9, IL-10, IL-13 and IFN-γ secretion induced from peripheral blood mononuclear cells (PBMC) by a broad panel of inhalant allergens (timothy, cat, birch, dog and house dust mite) in asthmatic children with and without sensitization. The study included 13 atopic asthmatic, 5 non-atopic asthmatic, and 12 non-atopic non-asthmatic children. PBMC were stimulated with allergens and cytokine production was measured with enzyme-linked immunosorbent assay (ELISA). Higher levels of cat and dog antigen-induced IL-5 release were more commonly observed in both atopic and non-atopic asthmatics than in controls. Children with atopic, but not non-atopic, asthma produced higher levels of allergen-induced IL-4 and IL-9 than controls. Non-atopic asthmatics produced more IL-10 than atopic asthmatics after cat stimulation. High levels of eosinophilia-associated IL-5 responses are induced by cat and dog allergen in both atopic and non-atopic asthmatic children. The Th2 cytokines IL-4 and IL-9 were associated only with atopic asthma, probably due to their IgE-inducing properties.

  • 37.
    Böttcher, Malin
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Fredriksson, Jenny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Hellquist, Anna
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Effects of breast milk from allergic and non-allergic mothers on mitogen- and allergen-induced cytokine production2003In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 14, no 1, 27-34 p.Article in journal (Refereed)
    Abstract [en]

    Breast milk contains several components that provide specific immunity and affect the maturation of the infant's immune system. The aim of this study was to analyze the effects of breast milk, on mitogen- and allergen-induced cytokine production from cord blood mononuclear cells (CBMC), and if those effects differ between allergic and non-allergic mothers. The cells were incubated for 96 h with phytohemagglutinin (PHA), ovalbumin or cat dander in the presence of various dilutions of colostrum. Colostrum inhibited both mitogen- and cat-induced IFN-γ and mitogen-induced interleukin-4 (IL-4) production. The inhibition on IFN-γ production was to some extent caused by TGF-β, as the effect was modified when an anti-TGF-β antibody was added to the cultures. In contrast, colostrum enhanced allergen-induced production of the Th2-like cytokines IL-5 and IL-13, and this was accompanied with increased production of IL-10. No differences were found between allergic and non-allergic mothers. The inhibitory effect of breast milk on IFN-γ production, which was partly due to the high levels of TGF-β, together with the enhancing effect on IL-10 secretion, confirm that breast milk is anti-inflammatory. Although the production of IL-5 and IL-13 was enhanced by colostrum, this was accompanied with an increased production of IL-10. Together with the high levels of TGF-β in breast milk and inhibitory effect of colostrum on IL-4 production, this suggests a possible mechanism whereby breast-feeding may protect against the development of allergy. Despite differences in the composition of breast milk between allergic and non-allergic mothers, the effects of breast milk on cytokine production from CBMC were independent of the atopic status of the mothers.

  • 38.
    Böttcher, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Häggström, Bo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Björksten, Bengt
    Jenmalm, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Total and allergen-specific immunoglobulin a levels in saliva in relation to the development of allergy in infants up to 2 years of age2002In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 32, no 9, 1293-1298 p.Article in journal (Refereed)
    Abstract [en]

    Background: The association between salivary IgA levels and development of allergy is controversial and the employed methodology has been questioned. Objective: The aim of the study was to relate the levels of total IgA, SIgA and allergen-specific IgA antibodies in saliva to the development of allergy in infants during the first 2 years of life. Methods: Saliva samples from 80 infants participating in a prospective study regarding the development of allergy were collected at 3 or 6, and 12 and 24 months of age. Total IgA, SIgA and Fel d 1 and ▀-lactoglobulin specific IgA levels were analysed with ELISA. Results: The levels of total IgA and SIgA increased with age. The number of samples with detectable IgA to Fel d 1 tended to increase with age, whereas the opposite was observed for IgA to ▀-lactoglobulin. Infants who developed allergy tended to have higher levels of total IgA, and allergen-specific IgA was more commonly detected than in non-allergic children. In contrast, non-allergic children tended to have higher levels of SIgA. Furthermore, the levels of SIgA were higher in sensitized infants with no allergic symptoms than in sensitized children with symptoms. Infants with allergic parents had lower SIgA levels than infants without. Direct exposure to cat and cow's milk did not influence the levels of allergen-specific IgA levels, nor was there any association between breast-feeding and IgA production. Conclusion: The kinetics of food and inhalant allergen-specific IgA in saliva during the first 2 years of life is similar to what has earlier been shown for IgG in serum. Development of allergy tended to be associated with high levels of total and allergen-specific IgA antibodies, but low levels of SIgA. Furthermore, high levels of SIgA seemed to protect sensitized children from developing allergic symptoms during the first 2 years of life, supporting a possible protective role of SIgA against development of allergy.

  • 39.
    Böttcher, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Jenmalm, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Breastfeeding and the development of atopic disease during childhood2002In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 32, no 2, 159-161 p.Article in journal (Refereed)
  • 40.
    Böttcher, Malin
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Center for Allergy Research and Institute of Environmental Medicine, Karolinska Institute, Karolinska, Sweden.
    Cytokine, chemokine and secretory IgA levels in human milk in relation to atopic disease and IgA production in infants2003In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 14, no 1, 35-41 p.Article in journal (Refereed)
    Abstract [en]

    The relationship between breast-feeding, IgA production and development of atopic disease in children is a matter of controversy. Some of this controversy might be due to individual differences in the composition of breast milk. The aim of this study was to relate the levels of cytokines, chemokines and secretory (S)-IgA antibodies in breast milk to the development of atopic manifestation and salivary IgA production in infants. Cytokine, chemokine and SIgA levels, as measured with enzyme-linked immunosorbent assay (ELISA), in colostrum and mature milk were analyzed in relation to the development of positive skin-prick tests (SPT), allergic symptoms and salivary IgA antibody production during the first 2 years of life in 53 infants. There was no association between levels of IL-4, -5, -6, -8, -10, -13, -16, IFN-γ, TGF-β1, -β2, RANTES, eotaxin or SIgA levels in the breast milk with either SPT-positivity, development of allergic symptoms or salivary IgA levels during the first 2 years of life in the infants. Thus, differences in the composition of cytokines, chemokines and SIgA in breast milk did not, to any major degree, affect the development of a positive SPT, atopic symptoms, nor salivary IgA antibody production during the first 2 years of life.

  • 41.
    Böttcher, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Jenmalm, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Garofalo, R
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Human milk polyunsaturated long-chain fatty acids and secretory immunoglobulin A antibodies and early childhood allergy2000In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 11, no 1, 29-39 p.Article in journal (Refereed)
    Abstract [en]

    The possible protective effect of breast milk against atopic manifestations in infancy, i.e. atopic eczema and food allergy, has been controversial for the last decades. Besides the methodological problems, differences in the composition of human milk could explain these controversies. The aim of this study was to investigate the composition of polyunsaturated fatty acids (PUFA) and secretory immunoglobulin A (S-IgA) levels to food proteins (ovalbumin and ▀-lactoglobulin) and an inhalant allergen (cat) in milk from mothers of allergic and non-allergic children. Blood samples were obtained at birth and at 3 months from 120 children. Skin prick tests were performed at 6, 12 and 18 months, and the development of atopic diseases was assessed in the children. Breast milk samples were collected from their mothers at birth and monthly during the lactation period. Milk PUFA composition was measured by gas chromatography, and enzyme-linked immunosorbent assay (ELISA) was used to measure total S-IgA, anti-cat S-IgA, anti-ovalbumin S-IgA, and anti-▀-lactoglobulin S-IgA. Allergic disease developed in 44/120 children (22/63 children of allergic mothers and 22/57 children of non-allergic mothers). Lower levels of eicosapentaenoic acid, C20:5 n-3 (EPA), docosapentaenoic acid C22:5 n-3 (DPA), and docosatetraenoic acid C22:4 n-6 (DHA) (p < 0.05 for all) were found in mature milk from mothers of allergic as compared to milk from mothers of non-allergic children. The total n-6 : total n-3 and the arachidonic acid, C20:4 n-6 (AA) : EPA ratios were significantly lower in transitional and mature milk from mothers of allergic children, as compared to milk from mothers of non-allergic children. The PUFA levels in serum of allergic and non-allergic children were largely similar, except for higher levels of C22:4 n-6 and C22:5 n-6 (p < 0.05 for both) and a higher AA:EPA ratio in serum phospholipids in the former group (p < 0.05). Changes in the levels of milk PUFA were reflected in changes in PUFA serum phospholipids, particularly for the n-6 PUFA. The AA:EPA ratio in maternal milk was related, however, to the AA:EPA only in serum from non-allergic children, while this was not the case in allergic children. The levels of total S-IgA, anti-cat S-IgA, anti-ovalbumin S-IgA, and anti-▀-lactoglobulin S-IgA in milk from mothers of allergic, as compared to non-allergic, children were similar through the first 3 months of lactation. Low levels of n-3 PUFA in human milk, and particularly a high AA:EPA ratio in maternal milk and serum phospholipids in the infants, were related to the development of symptoms of allergic disease at 18 months of age. The milk PUFA composition influenced the composition of PUFA in serum phospholipids of the children. We also showed that the lower levels of colostral anti-ovalbumin S-IgA and lower total S-IgA in mature milk from atopic mothers did not influence the development of allergic disease in the children up to 18 months of age. The findings indicate that low a-linolenic acid, C18:3 n-3 (LNA) and n-3 long-chain polyunsaturated fatty acids (LCP) 20-22 carbon chains, but not the levels of S-IgA antibodies to allergens, are related to the development of atopy in children.

  • 42.
    Böttcher, Malin
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Garofalo, Roberto P.
    Department of Pediatrics, Division of Immunology/Allergy/Rheumatology, University of Texas Medical Branch, Galveston, USA.
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Cytokines in breast milk from allergic and nonallergic mothers2000In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 47, no 1, 157-162 p.Article in journal (Refereed)
    Abstract [en]

    The allergy-preventing effect of breast-feeding remains controversial, possibly because of individual variations in the composition of the breast milk. The aim of this study was to investigate the concentrations of cytokines involved in allergic reactions and IgA antibody production in breast milk from allergic and nonallergic mothers. The cytokine concentrations were determined in colostrum and 1-mo milk samples from 24 mothers with, and 25 mothers without, atopic symptoms, using commercial ELISA kits. The immunosuppressive cytokine transforming growth factor-β was predominant and was detectable in all milk samples. IL-6 was detected in the majority of colostral and mature milk samples, whereas the other cytokines were less commonly detected. The concentrations of IL-6, IL-10, and transforming growth factor-β, which are all involved in IgA synthesis, correlated with each other and with total IgA concentrations in colostrum. The concentrations of IL-4 were higher in colostrum from allergic than nonallergic mothers, and similar trends were seen for IL-5 and IL-13. In conclusion, transforming growth factor-β and IL-6 were the predominant cytokines in human milk. The correlation between the concentrations of cytokines involved in IgA synthesis, i.e. IL-10, IL-6, and transforming growth factor-β, may explain the stimulatory effect on IgA production in breast-fed babies. Varying concentrations of IL-4, IL-5, and IL-13 may explain some of the controversy regarding the possible allergy-preventive effect of breast-feeding.

  • 43.
    Böttcher, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Norin, EK
    Sandin, A
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Microflora associated characteristics in faeces from allergic and non-allergic infants.2000In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 30, 1591-1597 p.Article in journal (Refereed)
  • 44.
    Casas, Rosaura
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Transfer of humoral immunity from the mother to her off-spring2001Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background. It has been established that T cell responses of foetal origin to inhalant allergens are present in most cord blood samples. These immune responses could possibly be explained by transplacental passage of peptides, either as free antigens or in complexes with IgG, providing the foetus with a trigger for the priming of the T cell system already in utero. Antibodies to food antigens to which the mother is commonly exposed are present in the milk, but their relationship to allergy is unknown. IgA antibodies to inhalant allergens have not been previously detected in human milk.

    Objective. The aim of this thesis was to explore whether inhaled allergens in serum and IgA antibodies in breast milk could contribute to the allergic immune responses to allergens in the children.

    Methods. The presence of cat allergen Fel d 1 was analysed by ELISA in serum samples from cat allergic asthmatic children. To detect IgG immune complexes (IC), affmity chromatography purification and Western blotting were performed. Iri:nnune complexes with Fel d 1-IgE were detected by a modification of MagicLite, and their specificity was assessed by different approaches. Serum samples from allergic and non-allergic mothers, and cord blood from their infants, were measured for the presence of Fel d 1-IgG immune complexes by an amplified ELISA. Cord blood mononuclear cells (CBMC) of babies from allergic and non-allergic mothers were stimulated with cat allergen and the production of IFN-γ, IL-5, IL-10 and IL-13 was determined by ELISA and the levels related to the presence of IC. Furthermore, IgG1 and IgG4 antibodies to cat were measured by ELISA. Colostrum and samples of mature milk from allergic and non-allergic mothers were analysed for IgA antibodies to cat, P-lactoblobulin (BLG) and ovalbumin (OVA) by an amplified ELISA.

    Results. The cat allergen Fel d I was detected in 70% of sera from cat allergic chilch'en, but not in any of the controls. The allergen was present in complexes with IgE and IgG antibodies as corroborated by different approaches. Immune complexes with IgG were detected in sera from allergic and non-allergic mothers, as well as in the cord blood from their babies, but neither the prevalence nor the levels of complexes were related to maternal allergy. This was also the case for IgG antibodies to cat. The production of IL-5, IL-10, IL-13 and IFN-γ by CBMC was not influenced by maternal atopy. Interferon-y secretion by CBMC after stimulation with cat allergen, however, was less conunonly detected in samples with immune complexes. Secretory IgA to cat and OVA allergens were frequently detected in colostrum and mature milk, while antibodies to BLG were less common. The antibody levels to cat and BLG were similar in allergic and non-allergic mothers.

    Conclusion. The presence of IC with allergens may contribute to maintaining immune responsiveness and sensitivity in allergic individuals. Low levels of transplacentally transferred IC can conceivable provide the foetus with the signal for priming ofT cell responses to inhalant allergens. This seems to be a nonnal mechanism, as the immune responses are not related to maternal allergy. Low level exposure of the maternal mucosa, e.g. by inhalant allergens, can induce IgA antibody secretion in breast milk, but this mechanism is not related with any protective effect against allergy.

    List of papers
    1. Circulating cat allergen and immune complexes in cat- allergic children
    Open this publication in new window or tab >>Circulating cat allergen and immune complexes in cat- allergic children
    Show others...
    1998 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 28, no 10, 1258-1263 p.Article in journal (Refereed) Published
    Abstract [en]

    Background

    The first encounters with allergens seem to influence the development of allergy. Food antigens have been detected in sera as free antigens and in complexes with IgG but less is known about the presence of inhalant allergens.

    Objective

    To investigate the presence of the major cat allergen Fel d 1, either as free allergen and/or in complexes with IgG and IgE antibodies in sera from atopic children.

    Methods

    Serum samples from 33 cat allergic asthmatic children, 7–17 years old, and 15 non-allergic controls were investigated for the presence of Fel d 1 by ELISA (detection limit 0.13 μg/L). To detect immune complexes (IC), the IgG fraction from Fel d 1 positive sera was purified by affinity chromatography. Purified and non-absorbed material was then analysed for allergen content and specific IgG antibody levels. Immune complexes with Fel d 1 IgE were detected by coupling anti-Fel d 1 MoAb to paramagnetic particles.

    Results

    Fel d 1 was detected (0.15–1.8 μg/L) in 23 of the 33 patients (70%) but not from any of the controls. Eighteen samples contained IgE-Fel d 1 IC and two of four tested samples contained Fel d 1 in the IgG fraction. Electrophoresis and Western blotting of IgG purified material using anti-Fel d 1 MoAb corroborated the presence of IgG-Fel d 1 IC.

    Conclusion

    Free-circulating inhalant allergen and IC with allergens may contribute to maintaining immune responsiveness and sensitivity.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-80093 (URN)10.1046/j.1365-2222.1998.00384.x (DOI)
    Available from: 2012-08-20 Created: 2012-08-20 Last updated: 2017-12-07Bibliographically approved
    2. Presence of Fel d 1 - IgE immune complexes in sera from cat allergic individuals
    Open this publication in new window or tab >>Presence of Fel d 1 - IgE immune complexes in sera from cat allergic individuals
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: We have recently reported the presence of immune complexes (IC) with the inhalant allergen Fel d I, in serum samples from cat allergic children. It was not entirely excluded however that these findings were due to the presence of human antibodies against cat serum albumin. The objective of this work was to confirm the presence of the major cat allergen Fel d I in complexes with IgE and to assess the specificity of the human IgE antibodies to cat allergen.

    Methods: Serum samples from 27 cat allergic children were investigated. For the detection of Fel d 1-IgE IC, a chemiluminescent immunoassay was modified by coupling an anti-Fel d I monoclonal antibody to paramagnetic particles. Levels of IgE antibodies to cat allergens were determined by chemiluminiscense and RAST, and IgG4 antibody levels by RAST.

    Results: Fifteen samples contained IgE-Fel d I IC. The levels of IC correlated with the levels of specific lgE antibodies to cat allergen correlated (r=0.48; p<0.05). All the samples of the 27 cat allergic children contained IgE and IgG4 antibodies against cat allergen, while IgE and IgG4 antibodies to cat serum were only demonstrated in 4/27 (14 %) and 6/27 (22%) samples respectively. Conclusions: Immune complexes with the major cat allergen, Fel d I, were commonly present in serum samples from cat allergic children.

    Keyword
    Allergen, Fel d 1, cat serum albumin, IgE, IgG, IgG4, immune complex
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-80113 (URN)
    Available from: 2012-08-21 Created: 2012-08-21 Last updated: 2012-08-21Bibliographically approved
    3. Detection of Fel d 1–immunoglobulin G immune complexes in cord blood and sera from allergic and non-allergic mothers
    Open this publication in new window or tab >>Detection of Fel d 1–immunoglobulin G immune complexes in cord blood and sera from allergic and non-allergic mothers
    2001 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, no 2, 59-64 p.Article in journal (Refereed) Published
    Abstract [en]

    It is an established fact that T-cell responses of fetal origin to inhalant allergens are present in most cord blood samples. These immune responses could be explained by trans-placental passage of peptides, either as free antigens or in complexes with immunoglobulin G (IgG), providing the fetus with a trigger for priming the T-cell system already present in utero. The aim of this study was to investigate the presence of the major cat allergen, Fel d 1, in complexes with IgG in cord blood and maternal sera. Serum samples from 75 mothers (38 allergic, 37 non-allergic), and cord blood from their infants, were investigated for the presence of Fel d 1–IgG immune complexes (ICs) by using an amplified enzyme-linked immunosorbent assay (ELISA). Three monoclonal antibodies to Fel d 1 were used for coating. The specificity of the method was confirmed by inhibition experiments. ICs of Fel d 1–IgG were detected in the sera of 45% allergic and 49% non-allergic mothers, and in, respectively, 34% and 41% of their infants. Therefore, neither the prevalence nor the level of ICs were affected by maternal allergy. Low levels of trans-placentally transferred ICs can provide the fetus with a signal for the priming of T-cell responses to inhalant allergens. However, this is not necessarily related to allergic disease.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25850 (URN)10.1034/j.1399-3038.2001.012002059.x (DOI)10287 (Local ID)10287 (Archive number)10287 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    4. Detection of Fel d 1–immunoglobulin G immune complexes in cord blood and sera from allergic and non-allergic mothers
    Open this publication in new window or tab >>Detection of Fel d 1–immunoglobulin G immune complexes in cord blood and sera from allergic and non-allergic mothers
    2001 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, no 2, 59-64 p.Article in journal (Refereed) Published
    Abstract [en]

    It is an established fact that T-cell responses of fetal origin to inhalant allergens are present in most cord blood samples. These immune responses could be explained by trans-placental passage of peptides, either as free antigens or in complexes with immunoglobulin G (IgG), providing the fetus with a trigger for priming the T-cell system already present in utero. The aim of this study was to investigate the presence of the major cat allergen, Fel d 1, in complexes with IgG in cord blood and maternal sera. Serum samples from 75 mothers (38 allergic, 37 non-allergic), and cord blood from their infants, were investigated for the presence of Fel d 1–IgG immune complexes (ICs) by using an amplified enzyme-linked immunosorbent assay (ELISA). Three monoclonal antibodies to Fel d 1 were used for coating. The specificity of the method was confirmed by inhibition experiments. ICs of Fel d 1–IgG were detected in the sera of 45% allergic and 49% non-allergic mothers, and in, respectively, 34% and 41% of their infants. Therefore, neither the prevalence nor the level of ICs were affected by maternal allergy. Low levels of trans-placentally transferred ICs can provide the fetus with a signal for the priming of T-cell responses to inhalant allergens. However, this is not necessarily related to allergic disease.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25850 (URN)10.1034/j.1399-3038.2001.012002059.x (DOI)10287 (Local ID)10287 (Archive number)10287 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    5. Cat allergen-induced cytokine secretion and Fel d 1–immunoglobulin G immune complexes in cord blood
    Open this publication in new window or tab >>Cat allergen-induced cytokine secretion and Fel d 1–immunoglobulin G immune complexes in cord blood
    2004 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 34, no 4, 591-596 p.Article in journal (Refereed) Published
    Abstract [en]

    Background We have recently obtained evidence for the presence of immune complexes (IC) in cord blood from allergic and non-allergic mothers. Such complexes could conceivably provide the fetus with the initial trigger for the priming of the T cell system already in utero.

    Objective To relate the presence of Fel d 1–IgG IC to T cell cytokine production in cord blood mononuclear cells (CBMCs) after stimulation with cat allergen.

    Methods CBMC obtained from babies of 15 allergic and 22 non-allergic mothers were cultured in the presence of cat allergen. The production of IFN-γ, IL-5, IL-10 and IL-13 was determined by ELISA. Furthermore, IgG1 and IgG4 antibodies to cat allergen in cord blood samples were measured by ELISA. A more sensitive ELISA was used to measure Fel d 1–IgG IC.

    Results The prevalence and levels of IC were similar in cord blood from children of allergic and non-allergic mothers. The production of IL-5, IL-10. IL-13 and IFN-γ by CBMC was not influenced by maternal atopy, but IFN-γ was less commonly detected in samples with IC. There was no association between the presence of IC and any other cytokines. The levels of IgG1 and IgG4 antibodies were similar in both groups, and tended to be associated with the presence of IC.

    Conclusion Immune complexes in cord blood may represent a normal mechanism for inducing primary immune responses, as the responses in babies from allergic and non-allergic mothers were largely similar. Low levels of IFN-γ seems to be related with the presence of IC in cord blood.

    Keyword
    allergen, cord blood, cytokine, Fel d 1, IgG, immune complex
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-22341 (URN)10.1111/j.1365-2222.2004.1924.x (DOI)1542 (Local ID)1542 (Archive number)1542 (OAI)
    Note
    On the day of the defence day the status of this article was submitted.Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
  • 45.
    Casas, Rosaura
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Björkstén, B
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Cat-specific IgA antibodies in breast milk from atopic and non-atopic mothers: detection of Fel D 1->IgG immune complexes in cord blood and sera.1999In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 118, 317-318 p.Article in journal (Refereed)
  • 46.
    Casas, Rosaura
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Detection of Fel d 1–immunoglobulin G immune complexes in cord blood and sera from allergic and non-allergic mothers2001In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, no 2, 59-64 p.Article in journal (Refereed)
    Abstract [en]

    It is an established fact that T-cell responses of fetal origin to inhalant allergens are present in most cord blood samples. These immune responses could be explained by trans-placental passage of peptides, either as free antigens or in complexes with immunoglobulin G (IgG), providing the fetus with a trigger for priming the T-cell system already present in utero. The aim of this study was to investigate the presence of the major cat allergen, Fel d 1, in complexes with IgG in cord blood and maternal sera. Serum samples from 75 mothers (38 allergic, 37 non-allergic), and cord blood from their infants, were investigated for the presence of Fel d 1–IgG immune complexes (ICs) by using an amplified enzyme-linked immunosorbent assay (ELISA). Three monoclonal antibodies to Fel d 1 were used for coating. The specificity of the method was confirmed by inhibition experiments. ICs of Fel d 1–IgG were detected in the sera of 45% allergic and 49% non-allergic mothers, and in, respectively, 34% and 41% of their infants. Therefore, neither the prevalence nor the level of ICs were affected by maternal allergy. Low levels of trans-placentally transferred ICs can provide the fetus with a signal for the priming of T-cell responses to inhalant allergens. However, this is not necessarily related to allergic disease.

  • 47.
    Casas, Rosaura
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Presence of Fel d 1 - IgE immune complexes in sera from cat allergic individualsManuscript (preprint) (Other academic)
    Abstract [en]

    Background: We have recently reported the presence of immune complexes (IC) with the inhalant allergen Fel d I, in serum samples from cat allergic children. It was not entirely excluded however that these findings were due to the presence of human antibodies against cat serum albumin. The objective of this work was to confirm the presence of the major cat allergen Fel d I in complexes with IgE and to assess the specificity of the human IgE antibodies to cat allergen.

    Methods: Serum samples from 27 cat allergic children were investigated. For the detection of Fel d 1-IgE IC, a chemiluminescent immunoassay was modified by coupling an anti-Fel d I monoclonal antibody to paramagnetic particles. Levels of IgE antibodies to cat allergens were determined by chemiluminiscense and RAST, and IgG4 antibody levels by RAST.

    Results: Fifteen samples contained IgE-Fel d I IC. The levels of IC correlated with the levels of specific lgE antibodies to cat allergen correlated (r=0.48; p<0.05). All the samples of the 27 cat allergic children contained IgE and IgG4 antibodies against cat allergen, while IgE and IgG4 antibodies to cat serum were only demonstrated in 4/27 (14 %) and 6/27 (22%) samples respectively. Conclusions: Immune complexes with the major cat allergen, Fel d I, were commonly present in serum samples from cat allergic children.

  • 48.
    Casas, Rosaura
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Böttcher, Malin
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Duchén, Karel
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Detection of IgA antibodies to cat, β-lactoglobulin, and ovalbumin allergens in human milk2000In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 105, no 6 part 1, 1236-1240 p.Article in journal (Refereed)
    Abstract [en]

    Background: The relationship between the development of allergy during infancy and breast-feeding remains controversial. This controversy may be due to individual variations in the composition of human milk. Antibodies to food antigens to which the mother is commonly exposed are present in the milk, but their relationship to allergy is still unknown. IgA antibodies to inhalant allergens have not been previously detected.

    Objective: Our purpose was to analyze secretory IgA antibody levels to cat, β-lactoglobulin, and ovalbumin allergens in colostrum and mature milk in relation to maternal allergy.

    Methods: Colostrum and samples of mature milk were obtained after 1 and 3 months of lactation from 53 nursing mothers (17 allergic and 36 nonallergic mothers) and were analyzed for total secretory IgA levels by ELISA and secretory IgA antibodies to cat, β-lactoglobulin, and ovalbumin by an enzyme-amplified ELISA. The specificity of the assays was confirmed by inhibition experiments.

    Results: Secretory IgA to cat, β-lactoglobulin, and ovalbumin allergens were detected in colostrum as well as mature milk. The levels of secretory IgA to ovalbumin were lower in colostrum from allergic mothers with P = .016, whereas the levels to β-lactoglobulin and cat were similar in the 2 groups. IgA antibodies to ovalbumin were detected in 94% of the colostrum samples from allergic and in all samples from nonallergic mothers, in 82% and 96%, respectively at 1 month, and 53% and 65% at 3 months. Fewer samples had detectable secretory IgA antibodies to β-lactoglobulin than to ovalbumin and cat, and only 33% and 10% of the samples from the allergic and nonallergic mothers, respectively, remained positive at 3 months. All the allergic mothers had detectable IgA to cat in colostrum, whereas 83% and 73% of the samples were positive at 1 and 3 months. The corresponding numbers were 93%, 81%, and 81% in the nonallergic mothers (not significant).

    Conclusion: Even a low level of exposure of the mucosa (eg, by inhalant allergens) can induce antibody secretion into the milk, both in allergic and nonallergic mothers. (J Allergy Clin Immunol 2000;105:1236-40.)

  • 49.
    Casas, Rosaura
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Djerf, P.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Häggström, P.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ferrándiz, R.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björksten, B.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Circulating cat allergen and immune complexes in cat- allergic children1998In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 28, no 10, 1258-1263 p.Article in journal (Refereed)
    Abstract [en]

    Background

    The first encounters with allergens seem to influence the development of allergy. Food antigens have been detected in sera as free antigens and in complexes with IgG but less is known about the presence of inhalant allergens.

    Objective

    To investigate the presence of the major cat allergen Fel d 1, either as free allergen and/or in complexes with IgG and IgE antibodies in sera from atopic children.

    Methods

    Serum samples from 33 cat allergic asthmatic children, 7–17 years old, and 15 non-allergic controls were investigated for the presence of Fel d 1 by ELISA (detection limit 0.13 μg/L). To detect immune complexes (IC), the IgG fraction from Fel d 1 positive sera was purified by affinity chromatography. Purified and non-absorbed material was then analysed for allergen content and specific IgG antibody levels. Immune complexes with Fel d 1 IgE were detected by coupling anti-Fel d 1 MoAb to paramagnetic particles.

    Results

    Fel d 1 was detected (0.15–1.8 μg/L) in 23 of the 33 patients (70%) but not from any of the controls. Eighteen samples contained IgE-Fel d 1 IC and two of four tested samples contained Fel d 1 in the IgG fraction. Electrophoresis and Western blotting of IgG purified material using anti-Fel d 1 MoAb corroborated the presence of IgG-Fel d 1 IC.

    Conclusion

    Free-circulating inhalant allergen and IC with allergens may contribute to maintaining immune responsiveness and sensitivity.

  • 50.
    Casas, Rosaura
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Ferrándiz, RA
    Wihl, j-Å
    Fernández, B
    Dreborg, S
    Biologic activity of Dermatophagoides siboney and Blomia tropicalis allergens in exposed and unexposed mite-allergic individuals. Effect of patient selection on the biologic standardization of mite extracts.  1999In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 54, 392-396 p.Article in journal (Refereed)
1234567 1 - 50 of 455
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