Enterovirus RNA in serum is a risk factor for beta-cell autoimmunity and clinical type 1 diabetes: A prospective study

Recent prospective studies have documented serologically an increased frequ ency of enterovirus infections in prediabetic children, indicating that the se infections may initiate and accelerate the beta-cell damaging process se veral years before the clinical manifestation of type 1 diabetes. The aim o f the present study was to establish whether these serological findings wou ld be supported by the detection of enterovirus RNA in a unique prospective series of sera collected from prediabetic children 0-10 years before the m anifestation of clinical type 1 diabetes. Reverse transcription followed by polymerase chain reaction employing highly conserved primers among enterov iruses were used to amplify enteroviral sequences. Viral RNA was found in 2 2% (11/49) of follow-up samples from prediabetic children but in only 2% (2 /105) of those from controls (OR 14.9, P < 0.001). Persisting RNA positivit y was not observed in any of these children. The presence of enterovirus RN A was associated with concomitant increases in the levels of autoantibodies against islet cells (OR 21.7, P < 0.01) and glutamic acid decarboxylase (O R 15.4, P < 0.05), but not in the levels of antibodies against insulin or t he tyrosine phosphatase-like IA-2 protein. In contrast to the prediabetic c hildren, those with newly diagnosed type 1 diabetes were negative for enter ovirus RNA. The results thus complement previous serological data, suggesti ng that enterovirus infections are an important risk factor underlying type 1 diabetes and associated with the induction of beta-cell autoimmunity eve n years before symptoms appear. (C) 2000 Wiley-Liss, Inc.