Identification of tetraspanin-7 as a target of autoantibodies in type 1 diabetes

McLaughlin, Kerry A. and Richardson, Carolyn C. and Ravishankar, Aarthi and Brigatti, Cristina and Liberati, Daniela and Lampasona, Vito and Piemonti, Lorenzo and Morgan, Diana and Feltbower, Richard G. and Christie, Michael R. (2016) Identification of tetraspanin-7 as a target of autoantibodies in type 1 diabetes. Diabetes, 65 (6). pp. 1690-1698. ISSN 0012-1797

Full content URL: http://dx.doi.org/10.2337/db15-1058

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Abstract

The presence of autoantibodies to multiple islet autoantigens confers high risk for development of Type 1 diabetes. Four major autoantigens are established (insulin, glutamate decarboxylase, IA-2, and zinc transporter-8), but the molecular identity of a fifth, a 38kDa membrane glycoprotein (Glima), is unknown. Glima antibodies have been detectable only by immunoprecipitation from extracts of radiolabeled islet or neuronal cells. We sought to identify Glima to enable efficient assay of these autoantibodies. Mouse brain and lung were shown to express Glima. Membrane glycoproteins from extracts of these organs were enriched by detergent phase separation, lectin affinity chromatography and SDS-PAGE. Proteins were also immunoaffinity purified from brain extracts using autoantibodies from diabetic patients’ sera before SDS-PAGE. Eluates from gel regions equivalent to 38kDa were analyzed by LC-MS/MS for protein identification. Three proteins were detected in samples from the brain and lung extracts, and in the immunoaffinity purified sample, but not the negative control. Only tetraspanin- 7, a multipass transmembrane glycoprotein with neuroendocrine expression, had physical characteristics expected of Glima. Tetraspanin-7 was confirmed as an autoantigen by demonstrating binding to autoantibodies in Type 1 diabetes. We identify tetraspanin-7 as a target of autoimmunity in diabetes, allowing its exploitation for diabetes prediction and immunotherapy.

Keywords:diabetes, Autoimmunity, Autoantigens, JCOpen
Subjects:C Biological Sciences > C550 Immunology
A Medicine and Dentistry > A100 Pre-clinical Medicine
B Subjects allied to Medicine > B130 Pathology
Divisions:College of Science > School of Life Sciences
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ID Code:22469
Deposited On:08 Mar 2016 21:34

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