Autoimmunity to two forms of glutamate decarboxylase in insulin-dependent diabetes mellitus.
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.
Department of Psychiatry and Behavioral Sciences, University of California Los Angeles 90024.
D L
DL
Kaufman
M G
MG
Erlander
M
M
Clare-Salzler
M A
MA
Atkinson
N K
NK
Maclaren
A J
AJ
Tobin
D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D001341:Autonomic Nervous System / Q000276:immunology / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000209:etiology* / Q000276:immunology; D003929:Diabetic Neuropathies / Q000209:etiology / Q000276:immunology; D004770:Enterovirus / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007515:Islets of Langerhans / Q000201:enzymology / Q000276:immunology; D007527:Isoenzymes / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000276:immunology; D012689:Sequence Homology, Nucleic Acid; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D007527:Isoenzymes; D010455:Peptides; D014764:Viral Proteins; D005968:Glutamate Decarboxylase