Early childhood infections precede development of beta-cell autoimmunity and type 1 diabetes in children with HLA-conferred disease risk.

Abstract

The etiology of type 1 diabetes (T1D) is largely unknown. Infections and microbial exposures are believed to play a role in the pathogenesis and in the development of islet autoimmunity in genetically susceptible individuals. To assess the relationships between early childhood infections, islet autoimmunity, and progression to T1D in genetically predisposed children. Children with human leukocyte antigen (HLA)-conferred disease susceptibility (N=790; 51.5% males) from Finland (n = 386), Estonia (n = 322), and Russian Karelia (n = 82) were observed from birth up to the age of 3 years. Children attended clinical visits at the age of 3, 6, 12, 18, 24, and 36 months. Serum samples for analyzing T1D-associated autoimmune markers were collected and health data recorded during the visits. Children developing islet autoimmunity (n = 46, 5.8%) had more infections during the first year of life (3.0 vs 3.0, mean rank 439.1 vs 336.2; P = .001) and their first infection occurred earlier (3.6 vs 5.0 months; P = .005) than children with no islet autoimmunity. By May 2016, 7 children (0.9%) had developed T1D (progressors). Compared with non-diabetic children, T1D progressors were younger at first infection (2.2 vs 4.9 months; P = .004) and had more infections during the first 2 years of life (during each year 6.0 vs 3.0; P = .001 and P = .027, respectively). By 3 years of age, the T1D progressors had twice as many infections as the other children (17.5 vs 9.0; P = .006). Early childhood infections may play an important role in the pathogenesis of T1D. Current findings may reflect either differences in microbial exposures or early immunological aberrations making diabetes-prone children more susceptible to infections.