Antibodies to Glutamic Acid Decarboxylase and P2-C Peptides in Sera From Coxsackie Virus B4-Infected Mice and IDDM Patients

  1. Nando K Chatterjee
  1. New York State Department of Health, Wadsworth Center for Laboratories and Research Empire State Plaza, Albany, New York
  1. Address correspondence and reprint requests to Dr. Nando K. Chatterjee, New York State Department of Health, Wadsworth Center for Laboratories and Research, P.O. Box 509, Empire State Plaza, Albany, New York 12201–0509. J.H.'s current address is Department of Pathology, Albany Medical College Hospital, Union University, New Scotland Avenue, Albany, NY 12202.

Abstract

The possible role of amino acid sequence and epitope homologies between a protein P2-C of Coxsackie virus B4 and human GAD in the development of host-specific immune response in insulin-dependent diabetes mellitus (IDDM) (molecular mimicry) was investigated. Peptide antibodies to the P2-C protein, GAD65, and GAD67 were raised to analyze their immunoreactivity by enzyme-linked immunosorbent assay and immunoblotting with GAD purified from the brain and pancreas of mice that develop hyperglycemia after the infection. Additionally, antibody reactivity to these peptide antigens was assessed in sera from the virus-infected mice and IDDM patients. All three peptide antisera reacted very strongly with homologous peptides; P2-C antiserum cross-reacted with GAD65 as efficiently as GAD65 antiserum with P2-C, but no cross-reaction was detected between P2-C and GAD67 although cross-reaction between the two GADs was quite pronounced. P2-C antiserum immunocomplexed with GAD65 from mouse brain or pancreas, whereas GAD65 and GAD67 antisera both immunocomplexed with the two GADs from these sources. Most of the sera from virus-infected mice were reactive to brain and pancreas GAD65 and also to P2-C peptide, whereas some reacted to GAD65 and a few to GAD67 peptides. A number of IDDM sera reacted with mouse GAD65 and also with P2-C and GAD65 peptides, whereas only a few reacted with GAD67 peptide. The immunoreactivity of the mouse and IDDM sera to P2-C and GAD65 peptides was blocked by pre-adsorption with mouse GAD. The results suggest that molecular mimicry may play a role in the pathogenesis of the disease.

  • Received December 16, 1993.
  • Revision received July 6, 1994.
  • Accepted July 6, 1994.
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