Denise Walther1, Anne Eugster1, Sibille Jergens2, Anita Gavrisan3, Christina Weinzierl4, Tanja Telieps4, Christiane Winkler2, Anette G Ziegler2,3, Ezio Bonifacio5,6. 1. DFG Research Center for Regenerative Therapies Dresden, Faculty of Medicine, Technische Universität Dresden, Fetscherstrasse 105, 01307, Dresden, Germany. 2. Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany. 3. Forschergruppe Diabetes e.V., Neuherberg, Germany. 4. Institute of Diabetes and Obesity, Helmholtz Zentrum München, Neuherberg, Germany. 5. DFG Research Center for Regenerative Therapies Dresden, Faculty of Medicine, Technische Universität Dresden, Fetscherstrasse 105, 01307, Dresden, Germany. ezio.bonifacio@crt-dresden.de. 6. Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD), Technische Universität Dresden, Dresden, Germany. ezio.bonifacio@crt-dresden.de.
Abstract
AIMS/HYPOTHESIS: Autoantibodies to pancreatic beta cell proteins are markers of asymptomatic type 1 diabetes. The aim was to determine whether autoantibodies to the beta cell protein tetraspanin 7 would improve the ability to identify autoimmunity against pancreatic beta cells. METHODS: 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. RESULTS: Antibody binding was observed against the full length and external domains of tetraspanin 7, and was strongest 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 25 (21.9%) of 114 multiple autoantibody positive relatives. Progression to diabetes did not differ between multiple autoantibody positive relatives with and without tetraspanin 7 autoantibodies. CONCLUSIONS/ INTERPRETATION: Tetraspanin 7 is an autoantigen in type 1 diabetes. Tetraspanin 7 autoantibodies are a marker of type 1 diabetes, but provide minor additional value to existing autoantibodies in identifying beta cell autoimmunity.
AIMS/HYPOTHESIS: Autoantibodies to pancreatic beta cell proteins are markers of asymptomatic type 1 diabetes. The aim was to determine whether autoantibodies to the beta cell protein tetraspanin 7 would improve the ability to identify autoimmunity against pancreatic beta cells. METHODS: 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. RESULTS: Antibody binding was observed against the full length and external domains of tetraspanin 7, and was strongest 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 25 (21.9%) of 114 multiple autoantibody positive relatives. Progression to diabetes did not differ between multiple autoantibody positive relatives with and without tetraspanin 7 autoantibodies. CONCLUSIONS/ INTERPRETATION:Tetraspanin 7 is an autoantigen in type 1 diabetes. Tetraspanin 7 autoantibodies are a marker of type 1 diabetes, but provide minor additional value to existing autoantibodies in identifying beta cell autoimmunity.
Entities:
Keywords:
Autoantibodies; Glima 38; Tetraspanin 7; Type 1 diabetes mellitus
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