No evidence of abnormal regulation of antibody response to coxsackievirus B4 antigen in prediabetic children

Abstract

SUMMARYEnterovirus infections are a potential environmental trigger of the autoimmune process leading to clinical type 1 diabetes. It has been suggested that the risk of virus-induced beta-cell damage might be connected with a defect in humoral immune responsiveness to enteroviruses. In the present study we assessed whether such a defect in IgG responsiveness to coxsackievirus B4 antigen existed in young children who developed diabetes-associated autoantibodies during prospective observation from birth until the age of 18 months. IgG levels and maturation of antibody avidity were analysed in 21 children with autoantibodies and 41 control children who had experienced an equal number of enterovirus infections and were additionally matched for age, sex and HLA-DQB1 risk alleles for type 1 diabetes but had not produced diabetes-associated autoantibodies. IgG levels to coxsackievirus B4 were high in cord serum reflecting the presence of maternal antibodies. Mean IgG levels gradually decreased but began to increase after the age of 6 months, showing no significant difference between autoantibody positive and control children. The avidity of antibodies was strong in cord serum and decreased gradually during the first year of life when maternal antibodies disappeared. The avidity indices, which varied considerably from child to child, did not differ between the autoantibody-positive and -negative subjects. In conclusion, our data suggest that children affected by a beta-cell damaging autoimmune process show normal responses to coxsackievirus B4 antigens.

Enterovirus infections are associated with the induction of β‐cell autoimmunity in a prospective birth cohort study

“…Thus, it is very unlikely that any of these factors (or closely related factors) could have biased the comparisons between the case and control subjects. Fourth, in our previous studies, we have found that the regulation of antibody responsiveness to enterovirus antigens is quite normal in autoantibody-positive DIPP cases when analyzed after natural infections [Heino et al, 2001] or standardized immunization with inactivated poliovirus vaccine [Sadeharju et al, 2001]. This finding suggests that our results could not have been biased by abnormal immune responsiveness in case subjects.…”

Environmental factors in the development of Type 1 diabetes

“…Infections, especially in early childhood, may in fact prevent or delay disease [86]. In some studies, the frequency of childhood infections correlated inversely with the incidence of T1D [87][88][89][90][91]. As one example, the EURODIAB Substudy 2 Study showed Pre-school day-care attendance and a proxy measure for total infectious disease exposure in early childhood was found to be inversely associated with diabetes [92].…”

Avidity progression of dietary antibodies in healthy and coeliac children

“…Serum samples were obtained when the first biopsy was taken (untreated coeliac disease), in remission on a gluten-free diet (treated), and/or at relapse after reintroduction of gluten (challenged). Anti-blactoglobulin antibody levels and avidities were analysed in sera from 16 children with untreated disease (median age 12 months, range [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] and nine with treated disease (median age 35 months, range . Antigliadin antibody levels and avidities were measured in 16 untreated coeliac children (median age 15 months, range 10-24), 11 treated cases (median age 32 months, range 17-57) and in eight coeliac children at relapse on gluten challenge (median age 45 months, range 32-53).…”