Single-cell insights into immune dysregulation in rheumatoid arthritis flare versus drug-free remission

Immune-mediated inflammatory diseases (IMIDs) are typically characterised by relapsing and remitting flares of inflammation. However, the unpredictability of disease flares impedes their study. Addressing this critical knowledge gap, we used the experimental medicine approach of immunomodulatory drug withdrawal in rheumatoid arthritis (RA) remission to synchronise flare processes, allowing characterisation with unprecedented detail. We used single cell RNA sequencing to analyse the diversity and comparative longitudinal changes in paired circulating lymphocyte samples from 12 patients with RA in remission prior to drug cessation (on-drug remission) and after drug cessation (either off drug flare, or drug-free remission) as part of the Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) Study. CD3+CD4+CD45RO+PD1hi T cells, CD3+CD8+CD45RO+PD1hi T cells, and CD3-CD19+ B cells were isolated from peripheral blood mononuclear cells from patients with RA before and after csDMARD cessation, and analysed by scRNAseq using the BD Rhapsody platform