Echovirus 4 and Type 1 diabetes mellitus

Aims/hypothesis: To determine the association between exposure to enteroviruses and Type I diabetes. Methods: We measured neutralizing antibodies to the following enteroviruses: Coxsackievirus CA9, CB1, CB2, CB3, CB4, CB5, CB6, and Echovirus E4, E6, E9, E11 in the sera of (1) Type I diabetic patients at diagnosis (n = 33), (2) healthy offspring of parents with Type I diabetes without islet cell antibodies (ICA) (n = 43) and (3) normal controls (n = 57). All subjects were less than 20 years old. We performed the neutralization test determining the cytopathogenic effect on Vero cells. HLA DR serotyping was also performed in Group 2. Results: Type I diabetic patients showed a higher frequency (21.2%, p < 0.01) of neutralizing antibodies to E4 in relation to controls (1.8%), although there were no differences comparing with offspring of Type I diabetic patients (20.9%). Healthy offspring carrying Type I diabetes HLA DR susceptibility genes were also exposed to E4 (15.0%). High frequencies of neutralizing antibodies to most enteroviruses were found in the control group. Conclusion: This study shows the association between Type I diabetes and the presence of neutralizing antibodies to Echovirus 4, suggesting the possible participation of this virus as an environmental trigger of this autoimmune disease. Interestingly, our population displays high frequencies of exposure to enterovirus (including CB4) although them incidence for Type I diabetes is low (2.9 per 100,000 inhabitants).