Immune reactivity to the enzyme glutamic acid decarboxylase (GAD), a pancreatic islet autoantigen, is present at the diagnosis of insulin-dependent diabetes mellitus (IDDM). Because GAD is also highly expressed in the nervous system, we investigated the presence of autoantibodies to the isoform GAD65 in patients with diabetic neuropathy, which is a debilitating complication of the disease. We studied 39 patients with autonomic and somatic neuropathy, 28 patients matched for age and IDDM duration, and 13 patients with a shorter duration of IDDM, all with no diabetic complications, as well as 50 recently diagnosed diabetic patients, 23 neurologic patients with idiopathic autonomic failure unrelated to IDDM, and 72 healthy subjects. An immunoprecipitation radioligand assay was used to detect anti-GAD65 autoantibodies with in vitro transcribed and translated human islet GAD65 as antigen. Autoantibodies to GAD65 were present in 56% of the diabetic patients with neuropathy, 57% of the long-duration and 69% of the short-duration diabetic control subjects, 78% of the recently diagnosed patients, and 13% of the nondiabetic neuropathic patients. Among the diabetic patients with neuropathy, there was no correlation between the presence of anti-GAD65 antibodies and the presence of autoantibodies to sympathetic ganglia, vagus nerve, or adrenal medulla structures identified by immunofluorescence. Our study shows that anti-GAD65 antibodies are present in a high proportion of patients with diabetic neuropathy but are not exclusively associated with it, rendering it unlikely that they have a role as a disease marker or that they are pathogenetic. Our findings also show that humoral autoimmunity to GAD65 is a major feature of diabetes of long duration (up to 52 years), although the source of the persistent stimulus for this reaction and its significance remain to be established.
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Original Articles|
September 01 1994
High Prevalence of Autoantibodies to Glutamic Acid Decarboxylase in Long-Standing IDDM Is Not a Marker of Symptomatic Autonomic Neuropathy
Maria M Zanone;
Maria M Zanone
Immunology Department, King's College School of Medicine and Dentistry
London, U.K.
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Jacob S Petersen;
Jacob S Petersen
Hagedorn Research Institute
Gentofte, Denmark
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Mark Peakman;
Mark Peakman
Immunology Department, King's College School of Medicine and Dentistry
London, U.K.
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Christopher J Mathias;
Christopher J Mathias
Cardiovascular Medicine Unit, St. Mary's Hospital Medical School/Imperial College and Autonomic Unit, National Hospital and Institute of Neurology
London, U.K.
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Peter J Watkins;
Peter J Watkins
Diabetic Department, King's College Hospital
London, U.K.
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Thomas Dyrberg;
Thomas Dyrberg
Novo Nordisk
Novo Alle, Bagsvaerd, Denmark
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Diego Vergani
Diego Vergani
Immunology Department, King's College School of Medicine and Dentistry
London, U.K.
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Address correspondence and reprint requests to Dr. Diego Vergani, Immunology Department, King's College School of Medicine and Dentistry, Bessemer Road, London SE5 9PJ, U.K.
Diabetes 1994;43(9):1146–1151
Article history
Received:
February 02 1994
Revision Received:
May 19 1994
Accepted:
May 19 1994
PubMed:
8070615
Citation
Maria M Zanone, Jacob S Petersen, Mark Peakman, Christopher J Mathias, Peter J Watkins, Thomas Dyrberg, Diego Vergani; High Prevalence of Autoantibodies to Glutamic Acid Decarboxylase in Long-Standing IDDM Is Not a Marker of Symptomatic Autonomic Neuropathy. Diabetes 1 September 1994; 43 (9): 1146–1151. https://doi.org/10.2337/diab.43.9.1146
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