Diabetologie und Stoffwechsel 2016; 11 - LB9
DOI: 10.1055/s-0036-1584103

Tetraspanin 7 is a novel autoantigen in type 1 diabetes

D Walther 1, A Eugster 1, S Jergens 2, A Gavrisan 3, C Weinzerl 4, T Telieps 4, C Winkler 2, AG Ziegler 2, 3, E Bonifacio 1, 5
  • 1DFG Center for Regenerative Therapies Dresden, Faculty of Medicine, TU Dresden, Dresden, Germany
  • 2Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, TU München, Neuherberg, Germany
  • 3Forschergruppe Diabetes e.V., Neuherberg, Germany
  • 4Institute of Diabetes and Obesity, Helmholtz Zentrum München, Neuherberg, Germany
  • 5Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD), TU Dresden, Dresden, Germany

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.