THE ROLE OF ENTEROVIRAL INFECTIONS IN THE DEVELOPMENT OF IDDM - LIMITATIONS OF CURRENT APPROACHES

Enteroviruses have been examined for their possible role in the etiolo gy of IDDM for nearly 40 years, yet the evidence remains inconclusive. The mechanism of acute cytolytic infection of beta-cells, proposed by earlier studies, appears to be incompatible with the long preclinical period of autoimmunity preceding IDDM. Advances in molecular biology have improved our understanding of enteroviral biology and of potentia l alternative pathogenic mechanisms through which enteroviruses may ca use diabetes. The focus of future human studies will likely shift from people with IDDM to those with prediabetic autoimmunity to determine whether acute enteroviral infections can promote progression from auto immunity to overt diabetes. We propose that such studies use assays to detect enteroviral RNA, in addition to IgM serology. RNA assays can o vercome sensitivity and type-specificity limitations of IgM assays as well as identify diabetogenic strains of enteroviruses, if such exist. Evaluation of the role of enteroviruses in triggering beta-cell autoi mmunity in humans will require large prospective studies of young chil dren. The Diabetes Autoimmunity Study in the Young-one of very few suc h studies currently underway-is focusing on potential interactions bet ween HLA class II genes and enteroviral infections. Future studies wil l likely examine interactions between viral infections and non-HLA IDD M candidate genes, including those that may determine beta-cell tropis m of candidate viruses.