AB0062 ABUNDANCE AND ACTIVATION OF MEMORY B-CELLS CHARACTERIZE SYNOVITIS IN RHEUMATOID ARTHRITIS PATIENTS WITH EARLY TREATMENT RESPONSE

Background A relevant percentage of patients with rheumatoid arthritis (RA) do not respond to individual (40%) or all available disease modifying anti-rheumatic drugs DMARDs (5-20%). recent study using synovial bulk RNAseq from a phase 4 trial has shown that humoral immune response gene signatures are associated rituximab and tocilizumab [1]. Other biomarkers can predict early alternative still lacking. Objectives This study, performed in real-life clinical care setting, aimed at characterizing synovitis RA an drug on single-cell level identify potential molecular signatures. Methods Synovial tissue was obtained by ultrasound-guided biopsy inflamed joints. Four were defined as responders meeting the D2T EULAR definition criteria (median (IQR) number treatments 1.5 (1.25)) [2], but 2022 ACR/EULAR remission within 3 months DMARD started after biopsy. Five met 7 (1)). Two out five group went into following initiation (abatacept (n=1) upadacitinib (n=1)). Both groups fulfilled classification for RA. 6000 cells targeted encapsulation (10X Genomics workflow v3.1). Libraries sequenced NovaSeq6000. The R packages used: Cell Ranger, Seurat, Harmony, PCAtools. Results Clinical characteristics (sex, age, swollen joint count, C-reactive protein, body mass index, smoking status) comparable between two groups, except presence autoantibodies (all compared only one responder patient seropositive). received biopsy: methotrexate plus certolizumab (n=1), alone abatacept (n=2). Patients had median seven before 29,408 integrated scRNA-seq analysis (mean 3,267 quality control filtering per patient). Unsupervised dimensionality reduction showed 8 principal components (PCs) explaining variations expression samples. PC6 significantly responder/D2T categorization, accounting 6.72% sample variation. Immunoglobulin genes (IgH-, IgL-), Prostaglandin D2 Synthase (PTGDS) B-cell antigen receptor complex-associated protein alpha chain (CD79A) among top 100 treatment (PC6) (Figure 1A). Analysis average these revealed mostly B plasma 1B). Comparing proportions cell populations graph-based clustering no significant differences patients. Further primary also did show changes cells: NR4A1+ memory (B recently receiving stimulation) higher 48%±10 vs 36%±10, p-value = 0.0547) 1C). differentially expressed 62 (p-value<0.05, fold change > < 0.3). Still, six 1D). Conclusion Synovitis activation abundance cells. finding cohort is concordance previous results showing association [1] sets path future predicting References [1]Rivellese et al, Nat Med 28, 1256–1268 (2022) [2]Nagy al. ARD 80, 31-35 (2021) Acknowledgements: NIL. Disclosure Interests Alexandra Khmelevskaya: None declared, Miranda Houtman: Kristina Buerki: Chantal Pauli: Felice Rivellese: Edoardo Prediletto: Costantino Pitzalis: Oliver Distler Consultant of: Abbvie, Adrian Ciurea: Caroline Ospelt: Raphael Micheroli: declared.