Autoimmunity to two forms of glutamate decarboxylase in insulin-dependent diabetes mellitus.

Abstract

Insulin-dependent diabetes mellitus (IDDM) is thought to result from the autoimmune destruction of the insulin-producing beta cells of the pancreas. Years before IDDM symptoms appear, we can detect autoantibodies to one or both forms of glutamate decarboxylase (GAD65 and GAD67), synthesized from their respective cDNAs in a bacterial expression system. Individual IDDM sera show distinctive profiles of epitope recognition, suggesting different humoral immune responses. Although the level of GAD autoantibodies generally decline after IDDM onset, patients with IDDM-associated neuropathies have high levels of antibodies to GAD, years after the appearance of clinical IDDM. We note a striking sequence similarity between the two GADs and Coxsackievirus, a virus that has been associated with IDDM both in humans and in experimental animals. This similarity suggests that molecular mimicry may play a role in the pathogenesis of IDDM.

• Authors: D L Kaufman, M G Erlander, M Clare-Salzler, M A Atkinson, N K Maclaren, A J Tobin
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 89 Issue 1 Pg. 283-92 (Jan 1992) ISSN: 0021-9738 [Print] United States
• PMID: 1370298 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Autoantibodies
• Autoantigens
• Epitopes
• Isoenzymes
• Peptides
• Viral Proteins
• Glutamate Decarboxylase

Topics

• Amino Acid Sequence
• Autoantibodies (blood, immunology)
• Autoantigens (immunology)
• Autoimmunity (immunology)
• Autonomic Nervous System (immunology, pathology)
• Diabetes Mellitus, Type 2 (complications, etiology, immunology)
• Diabetic Neuropathies (etiology, immunology)
• Enterovirus (genetics, immunology)
• Epitopes (immunology)
• Glutamate Decarboxylase (genetics, immunology)
• Humans
• Islets of Langerhans (enzymology, immunology)
• Isoenzymes (immunology)
• Molecular Sequence Data
• Peptides (genetics, immunology)
• Sequence Homology, Nucleic Acid
• Viral Proteins (genetics, immunology)