Enterovirus antibody levels during the first two years of life in prediabetic autoantibody-positive children

Aims/hypothesis. We evaluated the role of enterovirus infections in the pat hogenesis of Type I (insulin-dependent) diabetes mellitus by monitoring ent erovirus antibody levels in prediabetic children who turned positive for di abetes-associated autoantibodies in a prospective birth cohort study. Methods. Serial serum samples taken during prospective observation starting at birth were analysed for IgG and IgA class antibodies against enteroviru s antigens including purified coxsackievirus B4, echovirus 11, poliovirus 1 and a synthetic enterovirus peptide antigen using enzyme immunoassay. Mate rnal samples taken at the end of the third month of pregnancy were also stu died. Analyses were done from 21 children who developed autoantibodies and from 104 autoantibody-negative control children who were matched for the ti me of birth, gender and HLA susceptibility alleles. For comparison, adenovi rus antibodies were also analysed from all samples collected. Results. IgG class enterovirus antibody levels were high in maternal sample s and in cord blood in both case and control children. After birth the IgG levels decreased reaching a nadir at the age of 6 months. No IgA class anti bodies were detected at birth but started to emerge postnatally. Antibody l evels did not differ between the autoantibody positive and the control chil dren during the first 6-months of life. From 6 months to 24 months of age, the autoantibody positive children had higher IgG and IgA levels against co xsackievirus B4, echovirus 11 and the synthetic enterovirus peptide antigen s than control children but poliovirus 1 and adenovirus antibodies were clo sely similar in the two groups. The difference between children with autoan tibodies and control children was predominantly seen among boys and among t hose with the HLA-DQB1*0302/x genotype. Conclusions/interpretation. Our data show that children who seroconverted f or diabetes-associated autoantibodies develop stronger humoral immune respo nses to coxsackievirus B4, echovirus 11 and a synthetic enterovirus peptide antigen than children who remained negative for autoantibodies. Poliovirus antibodies induced by uniform vaccinations did not differ between the pred iabetic and control children suggesting that the regulation of antibody res ponses to enteroviruses is not disturbed. Accordingly, the results imply a stronger enterovirus exposure in prediabetic children supporting the role o f enteroviruses in the pathogenesis of Type I diabetes.