Cord blood islet autoantibodies and seasonal association with the type 1 diabetes high-risk genotype

Objective: Human leukocyte antigen DQ (HLA-DQ) genetic factors and islet autoantibodies are strongly associated with type 1 diabetes (T1D) and are currently used to predict T1D. This study examined whether islet autoantibodies in the cord blood of newborns to nondiabetic mothers were associated with the (T1D) high-risk genotype HLA-DQ2/8, gestational infections or both. Study Design: Cord blood samples were taken from 33 683 newborns and used for HLA typing and analyses of islet autoantibodies. Parents completed questionnaires when the child was 2 months of age. Result: The prevalence of newborn islet autoantibodies consistently varied with season over 4 years (P < 0.0001); lowest in first quarter (1.2%) and highest in third (2.4%). Cord blood islet autoantibodies were associated with HLA-DQ2/8 in the second (OR, 2.30; P = 0.02), third (OR, 2.12; P = 0.008) and fourth quarters (OR, 2.49; P = 0.007), but not in the first (OR, 1.13). Reported gastroenteritis was additionally associated with islet autoantibodies in the third quarter (OR, 1.80, P = 0.04). Conclusion: An association between HLA and islet autoimmunity may depend on environmental exposure during pregnancy. Follow-up of mothers and children will determine risk of T1D.