Background: Rheumatoid arthritis (RA)-interstitial lung disease (ILD) affects up to 60% of individuals on CT and is a leading cause of mortality. Effective risk stratification and mechanistic understanding to tailor existing and emergent therapies are lacking.

Objectives: To investigate whether specific immune cell subsets characterise RA-ILD that could inform on underlying immunopathogenesis and targeted therapeutic strategies.

Methods: Spectral flow cytometry was used to profile peripheral blood immune cell subsets (30 B cell markers, 29 T cell markers, and 6 cytokines) across individuals with RA-ILD, RA and ILD as well as healthy controls (HC). Additionally, CD20 immunohistochemistry was performed on lung tissue from 13 RA patients (no known ILD) and 3 ILD patients, as well as on synovial tissue from 9 RA patients (no known ILD) and 1 RA-ILD patient, to assess B-cell infiltration.

Results: 13 ILD, 10 RA-ILD, 10 RA and 10 HC were recruited. Peripheral immune profiling revealed significant alterations in both B and T cell compartments across the groups. CD11c ⁺ B cells were expanded in RA-ILD compared to RA, while Tim-1 ⁺ B cells were elevated in RA-ILD relative to both RA and ILD. Changes in chemokine receptor expression were also observed, including significantly lower frequencies of CXCR3 ⁺ B cells and CD62L ⁺ CD4 ⁺ T cells in RA-ILD compared to HC. Additionally, analysis of lung and synovial tissue revealed the presence of B cell follicles in RA, RA-ILD and ILD samples.

Conclusions: Our findings reveal distinct peripheral T and B cell signatures in RA-ILD compared to RA, ILD and HC, while the presence of B cell follicles in lung and synovial tissue supports the role for the local lung immune environment in disease pathogenesis. Extending this work in a larger patient cohort will help elucidate the immune heterogeneity of RA-ILD.

REFERENCES: [1] Wijsenbeek, M., A. Suzuki, and T.M. Maher, Interstitial lung diseases. The Lancet, 2022. 400(10354): p. 769-786.

[2] Bendstrup, E., et al., Interstitial Lung Disease in Rheumatoid Arthritis Remains a Challenge for Clinicians. J Clin Med, 2019. 8(12).21

[3] Salciccioli, J.D., et al., Interstitial lung disease incidence and mortality in the UK and the European Union: an observational study, 2001–2017. ERJ Open Research, 2022. 8(3): p. 00058-2022.

Acknowledgments: NIL.

Disclosure of Interests: None declared.