ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1659

Shared Lung and Joint T Cell Repertoire in Early Rheumatoid Arthritis Driven by Cigarette Smoking

Koen Venken1, Matthias Jarlborg1, Frederik Stevenaert2, Thomas Malfait3, Carolien Vlieghe1, Yann Abraham2, Teddy Manuello1, Tine Decruy1, Stijn Van Hee1, Hans Wils2, Pieter Peeters2, Philippe Carron4, Filip Van den Bosch3, Viggo Van Tendeloo2, Bart Lambrecht1, Ruth Wittoek5, Peggy Jacques6 and Dirk Elewaut7, 1VIB Center for Inflammation Research - Ghent University, Ghent, Belgium, 2Janssen Research and Development, Beerse, Belgium, 3Ghent University Hospital, Ghent, Belgium, 4UZ Gent, Gent, Belgium, 5Dept. of Rheumatology, Ghent University Hospital, Ghent University, Ghent, Belgium, 6University Hospital of GHent, Gent, Belgium, 7Ghent University and VIB Center for Inflammation Research, Ghent, Belgium

Meeting: ACR Convergence 2024

Keywords: , , ,

Session Information

Date: Sunday, November 17, 2024

Title: Abstracts: RA – Etiology and Pathogenesis I

Session Type: Abstract Session

Session Time: 1:00PM-2:30PM

Background/Purpose: Cigarette smoking has been associated with the production of anti-citrullinated protein antibodies (ACPA) and an increased risk of developing rheumatoid arthritis (RA) in individuals carrying shared epitope (SE) containing HLA-DR4 alleles. Yet, little is known on the regional and systemic T cell dynamics in response to smoking and a potential link to T cell infiltration in inflamed synovia remains to be explored. In this study, we therefore sought to study T cell features in lung and inflamed joints in human RA disease.

Methods: We set up a unique framework to monitor T cells in paired bronchoalveolar lavage (BAL) fluid, blood and inflamed synovium tissue samples collected in a one-day procedure from 17 new onset treatment naïve ACPA+ RA patients. T cell receptor (TCR) repertoire of index-sorted tissue residing T cells was determined by single-cell TCR sequencing coupled to deep immunophenotyping via Freeviz modelling of flow cytometry data.

Results: A significant enrichment of CD4+ and CD8+ T cells was seen in synovial samples from smoking versus non-smoking patients, along with an increase in expanded T cell clonotypes and TCR richness and alpha-diversity. T cell clonal expansions in synovium and lung (BAL) samples were particularly pronounced among SE+ smokers, suggesting a synergistic gene-smoke risk. Strikingly, identical TCR clonalities were present in matched lung and joint samples of RA smokers, the majority being also detectable in circulation. This was mirrored by an increased clustering of lung and synovium TCRs across patients, suggesting a shared specificity by conserved motifs. The lung-joint shared T cell clonotypes showed a restricted TCR gene usage and exhibited a particular CD57hi effector profile within the inflamed synovium. 

Conclusion: These data are compatible with a model whereby smoking instigates the induction of an early wave of pathogenic T cells in genetically susceptible individuals at mucosal sites which evolves into joint inflammation. Collectively, the data indicate a profound interplay between a strong MHC predisposition, smoking and induction of autoimmunity by shaping the TCR repertoire.

Disclosures: K. Venken: None; M. Jarlborg: None; F. Stevenaert: Janssen Research and Development – J&J, 3; T. Malfait: None; C. Vlieghe: None; Y. Abraham: Janssen Research and Development – J&J, 3, 11; T. Manuello: None; T. Decruy: None; S. Van Hee: None; H. Wils: Janssen Research and Development – J&J, 3; P. Peeters: Janssen Research and Development – J&J, 3; P. Carron: None; F. Van den Bosch: AbbVie/Abbott, 2, 6, Amgen, 6, Eli Lilly, 2, Fresenius Kabi, 6, Galapagos, 2, Janssen, 6, Novartis, 6, UCB, 6; V. Van Tendeloo: Janssen Research and Development – J&J, 3, 11; B. Lambrecht: None; R. Wittoek: None; P. Jacques: None; D. Elewaut: None.

To cite this abstract in AMA style:

Venken K, Jarlborg M, Stevenaert F, Malfait T, Vlieghe C, Abraham Y, Manuello T, Decruy T, Van Hee S, Wils H, Peeters P, Carron P, Van den Bosch F, Van Tendeloo V, Lambrecht B, Wittoek R, Jacques P, Elewaut D. Shared Lung and Joint T Cell Repertoire in Early Rheumatoid Arthritis Driven by Cigarette Smoking [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/shared-lung-and-joint-t-cell-repertoire-in-early-rheumatoid-arthritis-driven-by-cigarette-smoking/. Accessed .

« Back to ACR Convergence 2024

ACR Meeting Abstracts - https://acrabstracts.org/abstract/shared-lung-and-joint-t-cell-repertoire-in-early-rheumatoid-arthritis-driven-by-cigarette-smoking/