Distinct antibody specificities to a 64-kD islet cell antigen in Type 1 diabetes as revealed by trypsin treatment

Christie, M. R. and Vohra, G. and Champagne, P. and Daneman, D. and Delovitch, T. L. (1990) Distinct antibody specificities to a 64-kD islet cell antigen in Type 1 diabetes as revealed by trypsin treatment. Journal of Experimental Medicine, 172 (3). pp. 789-794. ISSN 0022-1007

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Item Type:Article
Item Status:Live Archive

Abstract

Type 1 diabetes is associated with antibodies that immunoprecipitate a 64-kD islet cell membrane protein from detergent extracts of pancreatic islets. In this study we have determined whether mild trypsin treatment of islet membranes can release fragments of the antigen that bind antibodies in the serum of Type 1 diabetic patients. Partial tryptic proteolysis of 35Smethionine-labeled 64-kD antigen immunoprecipitated from detergent extracts of rat islets resulted in the formation of 50-, 40-, and 37-kD fragments. Similar sized fragments were recovered when sera from diabetic patients were employed to immunoprecipitate polypeptides solubilized by mild trypsin treatment of a particulate fraction of radiolabeled rat islets. Of 27 diabetic patients, 22 possessed antibodies to the 50-kD polypeptide and 21 to the 40- and 37-kD polypeptides. A positive association was found between 64k antibodies and antibodies to the 50-kD fragment but not between 64k antibodies and antibodies to the 40- or 37-kD fragments. Some 64k antibody negative patients possessed antibodies that efficiently immunoprecipitated the latter fragments. Serum from 25 of 27 (93%) diabetic patients immunoprecipitated at least one of three tryptic polypeptides. One of 20 nondiabetic controls immunoprecipitated a 50-kD polypeptide and all controls were negative for antibodies to 40- and 37-kD fragments. Thus, Type 1 diabetes is associated with the presence of at least two antibody reactivities to distinct determinants of the 64-kD antigen, and some patients may possess antibodies to a cryptic epitope on the detergent-solubilized molecule. These data suggest that the detection of antibodies (present in 93% of patients) to epitopes on tryptic polypeptides of the 64-kD antigen may be of even greater diagnostic value for the onset of Type 1 diabetes than analyses of antibodies reactive with the intact 64-kD antigen.

Keywords:autoantibody, pancreas islet antibody, trypsin, unclassified drug, antibody specificity, article, clinical article, human, human cell, immunoprecipitation, insulin dependent diabetes mellitus, priority journal, tissue culture, Adolescent, Adult, Animal, Animals, Newborn, Antibody Specificity, Antigens, Surface, Autoantibodies, Cell Membrane, Child, Child, Preschool, Diabetes Mellitus, Insulin-Dependent, Islets of Langerhans, Molecular Weight, Peptide Mapping, Rats, Reference Values, Support, Non-U.S. Gov't
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
Divisions:College of Science > School of Life Sciences
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ID Code:18167
Deposited On:10 Aug 2015 09:11

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