Shared lung and joint T cell repertoire in early rheumatoid arthritis driven by cigarette smoking
Authors' conclusion
The data indicate a profound interplay between a strong MHC predisposition, smoking and induction of autoimmunity by shaping the TCR repertoire.
Study context
- Population
- New-onset treatment naïve ACPA+ rheumatoid arthritis (RA) patients
- Participants
- 17 patients
- Comparison
- Smoking vs non-smoking patients
- Outcome
- T cell features in lung and inflamed joints
Methodological detailspaired bronchoalveolar lavage fluid, blood and synovium samples, single-cell T cell receptor (TCR) sequencing, deep immunophenotyping
- Paired bronchoalveolar lavage fluid, blood and synovium samples
- Single-cell TCR sequencing
- Deep immunophenotyping
Main finding
As reported in the abstract
- Significant enrichment of CD4+ and CD8+ T cells in synovial samples from smokers vs non-smokers, with more expanded T cell clonotypes
- Particularly pronounced among SE+ smokers, suggestive of a synergic gene-smoke effect
- Identical TCR clonalities in matched lung and joint samples of RA smokers, most also detectable in circulation
- Increased clustering of lung and synovium TCRs across patients, suggesting shared specificity by conserved motifs
- Lung-joint shared clonotypes showed restricted TCR gene usage and a 4-1BB+CD57 hi effector profile in inflamed synovium
Original publication
Shared lung and joint T cell repertoire in early rheumatoid arthritis driven by cigarette smoking. Ann Rheum Dis. Published 8 November 2024. doi:10.
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