Skip to main content
Top
Published in: Diabetologia 9/2016

01-09-2016 | Short Communication

Tetraspanin 7 autoantibodies in type 1 diabetes

Authors: Denise Walther, Anne Eugster, Sibille Jergens, Anita Gavrisan, Christina Weinzierl, Tanja Telieps, Christiane Winkler, Anette G. Ziegler, Ezio Bonifacio

Published in: Diabetologia | Issue 9/2016

Login to get access

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.
Literature
1.
go back to reference Aanstoot HK, Kang SM, Kim J et al (1996) Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD65 and IA2 marks the early phases of autoimmune response in type 1 diabetes. J Clin Invest 97:2772–2783CrossRefPubMedPubMedCentral Aanstoot HK, Kang SM, Kim J et al (1996) Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD65 and IA2 marks the early phases of autoimmune response in type 1 diabetes. J Clin Invest 97:2772–2783CrossRefPubMedPubMedCentral
2.
go back to reference Roll U, Turck CW, Gitelman SE et al (2000) Peptide mapping and characterisation of glycation patterns of the glima 38 antigen recognised by autoantibodies in type I diabetic patients. Diabetologia 43:598–608CrossRefPubMed Roll U, Turck CW, Gitelman SE et al (2000) Peptide mapping and characterisation of glycation patterns of the glima 38 antigen recognised by autoantibodies in type I diabetic patients. Diabetologia 43:598–608CrossRefPubMed
3.
go back to reference Winnock F, Christie MR, Batstra MR et al (2001) Autoantibodies to a 38-kDa glycosylated islet cell membrane-associated antigen in (pre)type 1 diabetes: association with IA-2 and islet cell autoantibodies. Diabetes Care 24:1181–1186CrossRefPubMed Winnock F, Christie MR, Batstra MR et al (2001) Autoantibodies to a 38-kDa glycosylated islet cell membrane-associated antigen in (pre)type 1 diabetes: association with IA-2 and islet cell autoantibodies. Diabetes Care 24:1181–1186CrossRefPubMed
4.
go back to reference McClaughlin K, Richardson CC, Ravishankar A et al (2016) Identification of tetraspanin-7 as a target of autoantibodies in type 1 diabetes. Diabetes. doi:10.2337/db15-1058 McClaughlin K, Richardson CC, Ravishankar A et al (2016) Identification of tetraspanin-7 as a target of autoantibodies in type 1 diabetes. Diabetes. doi:10.​2337/​db15-1058
5.
go back to reference Thümer L, Adler K, Bonifacio E et al (2010) German new onset diabetes in the young incident cohort study: DiMelli study design and first-year results. Rev Diabet Stud 7:202–208PubMedPubMedCentral Thümer L, Adler K, Bonifacio E et al (2010) German new onset diabetes in the young incident cohort study: DiMelli study design and first-year results. Rev Diabet Stud 7:202–208PubMedPubMedCentral
6.
go back to reference Ziegler AG, Bonifacio E, Babydiab-Babydiet Study Group (2012) Age-related islet autoantibody incidence in offspring of patients with type 1 diabetes. Diabetologia 55:1937–1993CrossRefPubMed Ziegler AG, Bonifacio E, Babydiab-Babydiet Study Group (2012) Age-related islet autoantibody incidence in offspring of patients with type 1 diabetes. Diabetologia 55:1937–1993CrossRefPubMed
7.
go back to reference Ziegler AG, Meier-Stiegen F, Winkler C, Bonifacio E, the TEENDIAB Study Group (2012) Prospective evaluation of risk factors for the development of islet autoimmunity and type 1 diabetes during puberty - TEENDIAB: study design. Pediatr Diabetes 13:419–424CrossRefPubMed Ziegler AG, Meier-Stiegen F, Winkler C, Bonifacio E, the TEENDIAB Study Group (2012) Prospective evaluation of risk factors for the development of islet autoimmunity and type 1 diabetes during puberty - TEENDIAB: study design. Pediatr Diabetes 13:419–424CrossRefPubMed
Metadata
Title
Tetraspanin 7 autoantibodies in type 1 diabetes
Authors
Denise Walther
Anne Eugster
Sibille Jergens
Anita Gavrisan
Christina Weinzierl
Tanja Telieps
Christiane Winkler
Anette G. Ziegler
Ezio Bonifacio
Publication date
01-09-2016
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 9/2016
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-016-3997-1

Other articles of this Issue 9/2016

Diabetologia 9/2016 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.