Journal article

Authors list: 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; Yazdi, Amir S.; Sitaru, Cassian; Garn, Holger; Eming, Rudiger; Fleischer, Sabine; Hertl, Michael

Publication year: 2024

Pages: 263-272.e8

Journal: Journal of Investigative Dermatology

Volume number: 144

Issue number: 2

ISSN: 0022-202X

eISSN: 1523-1747

Open access status: Green

DOI Link: https://doi.org/10.1016/j.jid.2023.07.025

Publisher: Elsevier

Abstract: 
Pemphigus vulgaris (PV) is an autoimmune blistering disorder of the skin and/or mucous membranes caused by IgG autoantibodies that predominantly target two transmembrane desmosomal cadherins: desmoglein (DSG)1 and DSG3. DSG-specific T cells play a central role in PV pathogenesis because they provide help to autoreactive B cells for autoantibody production. In this study, we characterized DSG3-specific peripheral T cells in a cohort of 52 patients with PV and 41 healthy controls with regard to cytokine profile and epitope specificity. By ELISpot analysis, type 2 T cells reactive with the DSG3 ectodomain were significantly increased in patients with PV compared with those in healthy controls. By dextramer analysis, CD4 thorn T cells specific for an epitope within the extracellular domain of DSG3, DSG3(206-220), were found at significantly higher frequencies in patients with PV than in HLA-matched healthy controls. T-cell recognition of two distinct DSG3 epitopes, that is, DSG3(206-220) and DSG3(378-392), correlated significantly, suggesting a synergistic effect in B-cell help. Immunization of HLADRB1*04:02-transgenic mice with PV 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 markers of disease activity and potential therapeutic targets in PV.

Harvard Citation style: Didona, D., Scarsella, L., Hudemann, C., Volkmann, K., Zimmer, C., Beckert, B., et al. (2024) Type 2 T-Cell Responses against Distinct Epitopes of the Desmoglein 3 Ectodomain in Pemphigus Vulgaris, Journal of Investigative Dermatology, 144(2), pp. 263-272.e8. https://doi.org/10.1016/j.jid.2023.07.025

APA Citation style: Didona, D., Scarsella, L., Hudemann, C., Volkmann, K., Zimmer, C., Beckert, B., Tikkanen, R., Korff, V., Kühn, K., Wienzek-Lischka, S., Bein, G., Di Zenzo, G., Böhme, J., Cunha, T., Solimani, F., Pieper, J., Juratli, H., Göbel, M., Schmidt, T., ...Hertl, M. (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. https://doi.org/10.1016/j.jid.2023.07.025