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Autoimmunity to Two Forms of Glutamate Decarboxylase in Insulin-dependent Diabetes Mellitus

Overview
Journal J Clin Invest
Specialty General Medicine
Date 1992 Jan 1
PMID 1370298
Citations 99
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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.

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References
1.
Ziegler A, Herskowitz R, Jackson R, Soeldner J, Eisenbarth G . Predicting type I diabetes. Diabetes Care. 1990; 13(7):762-5. DOI: 10.2337/diacare.13.7.762. View

2.
Baekkeskov S, Aanstoot H, Christgau S, Reetz A, Solimena M, Cascalho M . Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature. 1990; 347(6289):151-6. DOI: 10.1038/347151a0. View

3.
Rorsman P, Berggren P, Bokvist K, Ericson H, Mohler H, Ostenson C . Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels. Nature. 1989; 341(6239):233-6. DOI: 10.1038/341233a0. View

4.
Rabinowe S, Brown F, Watts M, Kadrofske M, Vinik A . Anti-sympathetic ganglia antibodies and postural blood pressure in IDDM subjects of varying duration and patients at high risk of developing IDDM. Diabetes Care. 1989; 12(1):1-6. DOI: 10.2337/diacare.12.1.1. View

5.
Oldstone M . Molecular mimicry as a mechanism for the cause and a probe uncovering etiologic agent(s) of autoimmune disease. Curr Top Microbiol Immunol. 1989; 145:127-35. DOI: 10.1007/978-3-642-74594-2_11. View