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DOI: 10.1055/s-0036-1584103
Tetraspanin 7 is a novel autoantigen in type 1 diabetes
Autoantibodies to pancreatic beta cell proteins are makers of asymptomatic type 1 diabetes. Tetraspanin 7 is a 38 kDa beta cell glycoprotein that is a candidate target of GLIMA autoantibodies. The aim was to determine whether tetraspanin 7 is a novel autoantibody in early type 1 diabetes.
Full length and external domain fragments of tetraspanin 7 were expressed as luciferase-tagged fusion proteins, and used in immunoprecipitation assays to measure autoantibodies in samples from 363 patients with type 1 diabetes at onset of disease, 503 beta cell autoantibody negative first degree relatives of patients, and 212 relatives with autoantibodies to insulin, glutamic acid decarboxylase, insulinoma antigen 2, or zinc transporter 8.
Antibody binding was observed against the full length and external domains of tetraspanin 7, but was greatest against the full length protein. Autoantibodies that could be inhibited by untagged tetraspanin 7 were detected in 5 (1%) of 503 autoantibody negative relatives, 3 (3.2%) of 94 autoantibody negative patients, 95 (35.3%) of 269 autoantibody positive patients, 1 (1%) of 98 single autoantibody positive relatives, and 27 (23.7%) of 114 multiple autoantibody positive relatives. Progression to diabetes was similar in multiple autoantibody relatives with and without tetraspanin 7 autoantibodies. We conclude that tetraspanin 7 is a novel type 1 diabetes-relevant autoantigen, and tetraspanin 7 autoantibodies are a marker of type 1 diabetes.