Recent enterovirus infection in type 1 diabetes: Evidence with a novel IgM method

Enterovirus (EV) infection has been associated with Type 1 (T1D) diabetes and on a few occasions virus could be isolated at onset of the disease. Using two such isolates as antigens in a quantitative PCR enhanced immunoassay (TlD-EV-QPIA) we have measured IgM antibodies against such potentially diabetogenic viruses in serum from 33 newly diagnosed T1D children, 24 siblings, and 27 healthy children. Sera were also analysed with regard to autoantibodies against GAD65, the cytokine TNF-alpha and the chemokine IP-10. EV-RNA detection was performed on peripheral blood mononuclear cells (PBMC). IgM antibodies against this "new" EV antigen were more frequent in serum from T1D children than in serum from siblings and/or controls (P<0.001). EV-RNA was detected more frequently in PBMC from T1D children than in healthy control children (P< 0.001) and also compared to the siblings (P<0.003). The cytokine TNF-alpha was less frequently detected in serum from the T1 D children compared with serum from siblings and/controls (P<0.001). A positive correlation was found between the results obtained with the TlD-EV-QPIA and the EV-PCR (P< 0.001). These findings are in line with earlier findings of an increased frequency of enteroviral infections in newly diagnosed T1D patients. In addition, we found that T1D children at onset of the disease had lower frequencies of the chemokine TNF-alpha in their serum than age- and sex-matched controls had, suggesting an impaired immune response.