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

• Published in: Journal of medical virology Vol. 59; no. 2; pp. 256 - 261
• Main Authors: Vreugdenhil, G R, Batstra, M R, Aanstoot, H J, Melchers, W J, Galama, J M
• Format: Journal Article
• Language: English
• Published: United States 01.10.1999
• Subjects: Antibodies, Viral - blood; Antibody Specificity; Autoantibodies - blood; Autoimmune Diseases - immunology; Autoimmune Diseases - virology; Child; Diabetes Mellitus - blood; Diabetes Mellitus - virology; Enterovirus B, Human - immunology; Glutamate Decarboxylase - immunology; Humans; Molecular Mimicry - immunology; Viral Proteins - immunology
• ISSN: 0146-6615
• DOI: 10.1002/(SICI)1096-9071(199910)59:2<256::AID-JMV21>3.3.CO;2-8

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.