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Gestational respira...
Gestational respiratory infections interacting with offspring HLA and CTLA-4 modifies incident β-cell autoantibodies
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- Lynch, Kristian F. (author)
- University of South Florida
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- Lee, Hye-Seung (author)
- University of South Florida
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- Törn, Carina (author)
- Lund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups,Skåne University Hospital
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- Vehik, Kendra (author)
- University of South Florida
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- Krischer, Jeffrey P. (author)
- University of South Florida
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- Larsson, Helena Elding (author)
- Lund University,Lunds universitet,Pediatrisk endokrinologi,Forskargrupper vid Lunds universitet,Paediatric Endocrinology,Lund University Research Groups,Skåne University Hospital
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- Haller, Michael J (author)
- Florida Museum Natural History
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- Hagopian, William A. (author)
- Pacific Northwest Research Institute
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- Rewers, Marian J. (author)
- University of Colorado
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- She, Jin-Xiong (author)
- Medical College of Georgia
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- Simell, Olli G (author)
- Turku University Hospital
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- Toppari, Jorma (author)
- University of Turku
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- Ziegler, Anette G. (author)
- Klinikum rechts der Isar,Helmholtz Zentrum München
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- Akolkar, Beena (author)
- National Institute of Diabetes and Digestive and Kidney Diseases
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Hyöty, Heikki (author)
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Bonifacio, Ezio (author)
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- Lernmark, Åke (author)
- Lund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
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- Elsevier BV, 2018
- 2018
- English.
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In: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411. ; 86, s. 93-103
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Abstract
Subject headings
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- β-cell autoantibodies against insulin (IAA), GAD65 (GADA) and IA-2 (IA-2A) precede onset of childhood type 1 diabetes (T1D). Incidence of the first appearing β-cell autoantibodies peaks at a young age and is patterned by T1D-associated genes, suggesting an early environmental influence. Here, we tested if gestational infections and interactions with child's human leukocyte antigen (HLA) and non-HLA genes affected the appearance of the first β-cell autoantibody. Singletons of mothers without diabetes (n = 7472) with T1D-associated HLA-DR-DQ genotypes were prospectively followed quarterly through the first 4 years of life, then semiannually until age 6 years, using standardized autoantibody analyses. Maternal infections during pregnancy were assessed via questionnaire 3-4.5 months post-delivery. Polymorphisms in twelve non-HLA genes associated with the first appearing β-cell autoantibodies were included in a Cox regression analysis. IAA predominated as the first appearing β-cell autoantibody in younger children (n = 226, median age at seroconversion 1.8 years) and GADA (n = 212; 3.2 years) in children aged ≥2 years. Gestational infections were not associated with the first appearing β-cell autoantibodies overall. However, gestational respiratory infections (G-RI) showed a consistent protective influence on IAA (HR 0.64, 95% CI 0.45-0.91) among CTLA4-(AG, GG) children (G-RI*. CTLA4 interaction, p = 0.002). The predominant associations of HLA-DR-DQ 4-8/8-4 with IAA and HLA-DR-DQ 3-2/3-2 with GADA were not observed if a G-RI was reported (G-RI*HLA-DR-DQ interaction, p = 0.03). The role of G-RI may depend on offspring HLA and CTLA-4 alleles and supports a bidirectional trigger for IAA or GADA as a first appearing β-cell autoantibody in early life.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Autoimmune diabetes
- Autoimmunity
- Glutamic acid decarboxylase
- HLA
- IA-2
- Insulin
- Type 1 diabetes
- β-cell autoantibodies
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Lynch, Kristian ...
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Lee, Hye-Seung
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Törn, Carina
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Vehik, Kendra
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Krischer, Jeffre ...
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Larsson, Helena ...
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show more...
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Haller, Michael ...
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Hagopian, Willia ...
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Rewers, Marian J ...
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She, Jin-Xiong
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Simell, Olli G
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Toppari, Jorma
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Ziegler, Anette ...
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Akolkar, Beena
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Hyöty, Heikki
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Bonifacio, Ezio
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Lernmark, Åke
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show less...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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Journal of Autoi ...
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Lund University