Analysis of antibody responses against coxsackie virus B4 protein 2C and the diabetes autoantigen GAD(65)

Type I diabetes mellitus results from the autoimmune destruction of insulin producing beta cells in the pancreas. Certain viral infections, especially those caused by coxsackie B viruses and related enteroviruses, have been a ssociated with the development of type I diabetes. The sequence homology be tween the coxsackie B4 virus nonstructural protein 2C (CVB4 p2C) and the ma jor diabetes autoantigen glutamic acid decarboxylase (GAD(65)) provides a b asis for the hypothesis of molecular mimicry. In this study, we investigate d the prevalence of antibodies directed against nonstructural enterovirus p roteins. In addition, a correlation of antibodies against CVB4 p2C and GAD( 65) was studied in diabetes patients and in healthy controls. Antibody reac tivity against CVB proteins was detected by immunoprecipitation of [S-35]-m ethionine-labelled viral proteins and GAD(65) antibodies were measured in a quantitative radio-immunoassay. It was shown that antibodies raised agains t the nonstructural proteins of CVB4 are very common in the population and a high degree of heterotypic cross-reactivity exists between different ente rovirus types. CVB4 p2C-specific antibodies were not only detectable in GAD (65) antibody-positive diabetes patients but also in GAD(65) antibody-negat ive healthy blood donors. Furthermore, GAD(65) antibodies could not be dete cted in p2C-positive subjects who had various enterovirus infections, indic ating that an antibody response to CVB4 p2C does not necessarily induce a c ross-reactive immune response against GAD(65). A correlation was not found between antibodies against GAD(65) and p2C. (C) 1999 Wiley-Liss, Inc.