Identification of tetraspanin-7 as a target of autoantibodies in type 1 diabetes
Open accessAbstract
The presence of autoantibodies to multiple-islet autoantigens confers high risk for the development of type 1 diabetes. Four major autoantigens are established (insulin, glutamate decarboxylase, IA2, and zinc transporter-8), but the molecular identity of a fifth, a 38-kDa membrane glycoprotein (Glima), is unknown. Glima antibodies have been detectable only by immunoprecipitation from extracts of radiolabeled islet or neuronal cells. We sought to identify Glima to enable efficient assay of these autoantibodies. Mouse brain and lung were shown to express Glima. Membrane glycoproteins from extracts of these organs were enriched by detergent phase separation, lectin affinity chromatography, and SDS-PAGE. Proteins were also immunoaffinity purified from brain extracts using autoantibodies from the sera of patients with diabetes before SDS-PAGE. Eluates from gel regions equivalent to 38 kDa were analyzed by liquid chromatography–tandem mass spectrometry for protein identification. Three proteins were detected in samples from the brain and lung extracts, and in the immunoaffinity-purified sample, but not in the negative control. Only tetraspanin-7, a multipass transmembrane glycoprotein with neuroendocrine expression, had physical characteristics expected of Glima. Tetraspanin-7 was confirmed as an autoantigen by demonstrating binding to autoantibodies in type 1 diabetes. We identify tetraspanin-7 as a target of autoimmunity in diabetes, allowing its exploitation for diabetes prediction and immunotherapy.
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Over 90% of people with newly diagnosed type 1 diabetes have measurable antibodies against specific β-cell proteins, including insulin, glutamate decarboxylase, islet antigen 2, zinc transporter 8, and tetraspanin-7.
“Over 90% of people with newly diagnosed type 1 diabetes have measurable antibodies against specific β-cell proteins, including insulin, glutamate decarboxylase, islet antigen 2, zinc transporter 8, and tetraspanin-7.14”
From Type 1 diabetes (2018) · cites this paper as [14]
The introduction (Takedown, p. 4) identifies insulin, glutamate decarboxylase, IA-2, and zinc transporter 8 as major autoantigens; the paper also confirms tetraspanin-7 as an autoantibody target (Takedown, p. 2). It does not establish that over 90% of newly diagnosed people have measurable antibodies to these proteins. (LLM, conf=0.88)
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- Authors
- McLaughlin, K. A., Richardson, C. C., Ravishankar, A., Brigatti, C., Liberati, D., Lampasona, V., Piemonti, L., Morgan, D., Feltbower, R. G., & Christie, M. R.
- Affiliations
- King's College London (GB)
- IRCCS Ospedale San Raffaele (IT)
- University of Leeds (GB)
- Corresponding author
- Christie, Michael R.
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2016-03-07
- Volume
- 65
- Issue
- 6
- Pages
- 1690-1698
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2293565227
- Cited by
- 113
- References
- 31
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 10 · 2023: 16 · 2022: 16 · 2021: 7 · 2020: 13 · 2019: 14 · 2018: 13 · 2017: 7 · 2016: 7
- FWCI
- 11.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Lincoln Repository (University of Lincoln) (acceptedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Figshare (submittedVersion, cc-by)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Diabetes UK (11/0004297)
- Society for Endocrinology (Early Career Award)
- Italian Ministry of Research
- King’s College London Graduate School
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- type 1 diabetes, autoantibodies, autoantigens, islet autoimmunity, autoantigen identification, immunoaffinity purification, transmembrane glycoprotein, diabetes prediction
- MeSH terms
- Adolescent, Adult, Animals, Autoantibodies, Autoantigens, Brain, Diabetes Mellitus, Type 1, Humans, Lung, Membrane Glycoproteins, Middle Aged, Mice, Tetraspanins
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