title: Analysis of antibody responses against coxsackie virus B4 protein 2C and the diabetes autoantigen GAD(65).
abstract: 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 associated with the development of type I diabetes. The sequence homology between the coxsackie B4 virus nonstructural protein 2C (CVB4 p2C) and the major diabetes autoantigen glutamic acid decarboxylase (GAD(65)) provides a basis for the hypothesis of molecular mimicry. In this study, we investigated the prevalence of antibodies directed against nonstructural enterovirus proteins. In addition, a correlation of antibodies against CVB4 p2C and GAD(65) was studied in diabetes patients and in healthy controls. Antibody reactivity against CVB proteins was detected by immunoprecipitation of [(35)S]-methionine-labelled viral proteins and GAD(65) antibodies were measured in a quantitative radio-immunoassay. It was shown that antibodies raised against the nonstructural proteins of CVB4 are very common in the population and a high degree of heterotypic cross-reactivity exists between different enterovirus types. CVB4 p2C-specific antibodies were not only detectable in GAD(65) antibody-positive diabetes patients but also in GAD(65) antibody-negative healthy blood donors. Furthermore, GAD(65) antibodies could not be detected in p2C-positive subjects who had various enterovirus infections, indicating that an antibody response to CVB4 p2C does not necessarily induce a cross-reactive immune response against GAD(65). A correlation was not found between antibodies against GAD(65) and p2C.
authors.affiliation: Department of Medical Microbiology, University of Nijmegen, Nijmegen, The Netherlands. g.vreugdenhil@mmb.azn.nl
authors.forename: G R
authors.initials: GR
authors.lastname: Vreugdenhil
authors.forename: M R
authors.initials: MR
authors.lastname: Batstra
authors.forename: H J
authors.initials: HJ
authors.lastname: Aanstoot
authors.forename: W J
authors.initials: WJ
authors.lastname: Melchers
authors.forename: J M
authors.initials: JM
authors.lastname: Galama
mesh_terms: D000914:Antibodies, Viral / Q000097:blood*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000276:immunology / Q000821:virology; D002648:Child; D003920:Diabetes Mellitus / Q000097:blood / Q000821:virology; D029822:Enterovirus B, Human / Q000276:immunology*; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D018716:Molecular Mimicry / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D001323:Autoantibodies; C089732:P2-C protein, Coxsackievirus; D014764:Viral Proteins; D005968:Glutamate Decarboxylase