Cigarette smoking is a risk factor for rheumatoid arthritis (RA), especially in individuals who share variants of the hypervariable region of HLA-DRβ chain that are known as ‘shared epitope’ alleles. An enhancement of protein citrullination in smokers has been suggested as underlying the emergence of anti-citrullinated protein antibodies (ACPAs) and, potentially, of RA, but the mechanisms by which smoking might break T cell tolerance to drive joint inflammation remain unclear.

Venken et al. addressed this by analysing the single-cell T cell receptor (TCR) repertoires and phenotypes of T cells isolated from lung and synovial samples of treatment-naive individuals newly diagnosed with ACPA positivity and early RA. “This was achieved by a joint coordinated effort between the rheumatology and pneumology departments in a one-day procedure including bronchoalveolar lavage upon bronchoscopy, venipuncture and ultrasound guided synovial biopsy sampling of inflamed joints”, notes first author Koen Venken.