Didona, Dario; Scarsella, Luca; Hudemann, Christoph; Volkmann, Karolin; Zimmer, Christine L; Beckert, Benedikt; Tikkanen, Ritva; Korff, Vera; Kühn, Katja; Wienzek-Lischka, Sandra; Bein, Gregor; di Zenzo, Giovanni; Böhme, Jaqueline; Cunha, Tomas; Solimani, Farzan; Pieper, Josquin; Juratli, Hazem A; Göbel, Manuel; Schmidt, Thomas; Borradori, Luca; ... (2024). Type 2 T cell responses against distinct epitopes of the desmoglein 3 ectodomain in pemphigus vulgaris. Journal of investigative dermatology, 144(2), 263-272.e8. Elsevier 10.1016/j.jid.2023.07.025
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Pemphigus vulgaris (PV) is an autoimmune blistering disorder of the skin and/or mucous membranes caused by IgG autoantibodies which predominantly target two transmembrane desmosomal cadherins, desmoglein (Dsg)1 and Dsg3. Dsg-specific T cells play a central role in PV pathogenesis as they provide help to autoreactive B cells for autoantibody production. We here characterized Dsg3-specific peripheral T cells in a cohort of 52 PV patients and 41 healthy controls (HC) with regard to cytokine profile and epitope specificity. By ELISpot analysis, type 2 T cells reactive with the Dsg3 ectodomain were significantly increased in PV patients compared to HC. By dextramer analysis, CD4+ T cells specific for an epitope within the extracellular domain of Dsg3, Dsg3(206-220), were found at significantly higher frequencies in PV patients than in HLA-matched HC. T cell recognition of two distinct Dsg3 epitopes, i.e. Dsg3(206-220) and Dsg3(378-392), correlated significantly suggesting a synergistic effect in B cell help. Immunization of HLA-DRB1*04:02-transgenic PV mice with the same set of Dsg3 peptides induced pathogenic Dsg3-specific IgG antibodies which induced loss of keratinocyte adhesion in vitro. Thus, Dsg3 peptide-specific T cells are of particular interest as surrogate marker of disease activity and potential therapeutic targets in PV.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology |
UniBE Contributor: |
Borradori, Luca |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1523-1747 |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
18 Sep 2023 14:12 |
Last Modified: |
15 Jan 2024 00:13 |
Publisher DOI: |
10.1016/j.jid.2023.07.025 |
PubMed ID: |
37717934 |
Uncontrolled Keywords: |
T cells autoimmunity bullous disease cytokines regulatory T cells |
BORIS DOI: |
10.48350/186375 |
URI: |
https://boris.unibe.ch/id/eprint/186375 |
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