Gestational respiratory infections interacting with offspring HLA and CTLA-4 modifies incident β-cell autoantibodies.

Gestational respiratory infections interacting with offspring HLA and CTLA-4 modifies incident β-cell autoantibodies. J Autoimmun. 2017 Sep 20;: Authors: Lynch KF, Lee HS, Törn C, Vehik K, Krischer JP, Larsson HE, Haller MJ, Hagopian WA, Rewers MJ, She JX, Simell OG, Toppari J, Ziegler AG, Akolkar B, Hyöty H, Bonifacio E, Lernmark Å, TEDDY Study Group Abstract 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 GA...
Source: Journal of Autoimmunity - Category: Allergy & Immunology Authors: Tags: J Autoimmun Source Type: research