Weber, A., Zulcinski, M., Haroon-Rashid, L. et al. (5 more authors) (2025) Identification of clonally expanded T-cell receptor sequences in giant cell arteritis. Journal of Autoimmunity, 151. 103372. ISSN 0896-8411
Abstract
Background
Arterial wall inflammation in giant cell arteritis (GCA) is characterized by T-cell infiltration and granuloma formation. There have been limited studies investigating the diversity of the T-cell receptor (TCR) repertoire in GCA patients. Here we aim to identify disease-relevant TCRs.
Methods
We sequenced the TCRβ repertoires in peripheral blood and biopsies from 72 GCA patients and compared them to repertoires of 60 age-matched controls. Applying K-nearest neighbours classification based on tcrdist3, an established TCR similarity measure, we identified GCA-associated TCRs across multiple model hyperparameters and experimental replicates.
Results
We observed that species richness and Shannon diversity were significantly lower (P = 0.0003 and P = 0.004, respectively) in GCA peripheral blood TCR repertoires compared with age-matched controls. 1526 TCRs were identified that were consistently associated with GCA, 63 TCRs were also detected in TAB repertoires. Identical GCA-associated TCRs were observed in paired blood and tissue samples from 21/30 GCA cases. 57 % of GCA-associated TCRs were fitted into 10 clusters, which displayed distinct TCR sequences and TCR V and J segment usage. TRBV20-1∗01, TRBV4-3∗01, TRBV4-2∗01 and TRBV4-1∗01 segments were over-represented and occurred at least 10 % more often among GCA patients than age-matched controls. Only 27/1526 TCR sequences had matches reported in public databases, reducing the likelihood that these targeted common infectious agents.
Conclusions
Our data provide evidence of circulating T-cell clonal expansions in GCA patients. Certain TCR sequence patterns were over-represented in GCA subjects. As more TCR sequences directed at human antigens become available, further analysis may ultimately reveal whether these TCRs bind a common target antigen.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | Giant cell arteritis, Vasculitis, T-cell receptor, T-cells, Pathogenesis |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Funding Information: | Funder Grant number EU - European Union 813545 NIHR National Inst Health Research Not Known NIHR National Inst Health Research NIHR202395 |
Depositing User: | Symplectic Publications |
Date Deposited: | 28 Jan 2025 11:42 |
Last Modified: | 17 Feb 2025 09:52 |
Published Version: | http://sciencedirect.com/science/article/pii/S0896... |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.jaut.2025.103372 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:222350 |
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