Effect of coincident enterovirus infection and cows' milk exposure on immunisation to insulin in early infancy

Aims/hypothesis. Insulin autoantibodies appear often as the first autoantibody in children who develop islet-cell autoimmunity. Our recent studies indicate that primary immunisation to insulin is induced in early infancy by exposure to dietary bovine insulin present in cows' milk formulas. As gut-associated lymphoid tissue is also the primary replication site of enteroviruses, we tested whether enterovirus infections could modify the development of immune response to dietary insulin in early infancy. Methods. We studied the development of IgG-antibodies to dietary bovine insulin by enzyme immunoassay in relation to enteroviral infections determined by T-cell proliferation response to the Coxsackie B4 virus and by serological tests for enterovirus antigens in 57 infants who carried the HLA DQB1*02/0302 diabetes risk genotype and participated in a Finnish population-based birth-cohort study (Diabetes Prediction and Prevention Project, DIPP, study). Results. In the infants exposed to cows' milk formulas before the age of 3 months, those who had a T-cell proliferation response to enterovirus antigen at 3 months of age (n = 12) had higher concentrations of IgG-antibodies to bovine insulin at the age of 6 and 9 months than those who did not have T-cell proliferation response to enterovirus antigen (n = 25) (median OD were 0.742 vs 0.427, p = 0.04, and 0.477 vs 0.293, p = 0.02, respectively). Conclusion/interpretation. Our results suggest that two epidemiological risk factors of Type I (insulin-dependent) diabetes mellitus, enterovirus infections and exposure to cows' milk formulas, could modify the immunisation to insulin in early infancy. [Diabetologia (2002) 45: ▪–▪]