AB0021 CHARACTERISATION OF AGE-ASSOCIATED B CELLS IN EARLY, DRUG NAÏVE RHEUMATOID ARTHRITIS

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease of immune dysregulation affecting the joints. While T cells play recognised role in pathogenesis, presence autoantibodies years before clinical onset disease, and efficacy B cell-depleting therapy rituximab, highlight pathogenic for these functionally diverse lymphocytes. A novel subset, termed age-associated (ABCs), are described as CD19 high CD21 - CD11c + , with proportion expressing transcription factor T-bet; they elevated murine models autoimmunity produce characteristic autoimmune disease. detailed characterisation ABCs early, drug naïve RA has not yet been conducted. Objectives: We aimed to characterise peripheral blood (PB) synovial fluid (SF) patients suffering from early RA. As secondary objective we sought determine whether this population differs between age-matched psoriatic (PsA; controls) healthy controls. Methods: Newly presenting other patients, immunomodulatory treatment, were recruited Newcastle Early Arthritis Clinic. Patients established (≥1 year duration on treatment controls parallel. cell subsets (naïve (CD19 IgD CD27 ), switched memory ) ABC )) PB SF characterised by flow cytometry. FACS sorted subset gene expression profiles assessed using customised NanoString nCounter Human Immunology v2 Panel. Results: Transcriptionally, differed both cells. In keeping published studies had an activated phenotype, exemplified CD69, CD80, CD86, well Ki67, HLA-DR, IgG T-bet. Interestingly, Fc Receptor Like (FcRL) family (FcRL1-5), homing profile (high levels CXCR3 low CXCR4 CXCR5). found no difference control groups, association frequencies age. Focussing specifically, observed females, but activity. their chemokine receptor profile, cross-sectional analysis also demonstrated enrichment compared PB, higher than The transcriptome donors (Figure 1 next page). Conclusion: These data demonstrate that have unique, activated, class-switched proliferative phenotype transcriptionally distinct at level differ counterparts health arthritides, suggesting may contribute pathogenesis. Of note, MHC class II (HLA-DR) co-stimulatory (CD80 CD86) molecules suggests important antigen-presentation function ABC, which together unique FcRL pattern, warrants further functional characterisation. Figure 1. Differential PsA (A) (B). Technologies chip was used assess expression. Raw counts normalised housekeeping genes. Sample quality then arrayQualityMetrics package. Gene different donor groups DESeq2 R hierarchical clustering heatmaps intensities log2 transformed z-scores displayed colours ranging yellow (low expression) red shown key. Disclosure Interests: Gemma Vidal-Pedrola: None declared, Najib Naamane: Dagmar Scheel-Toellner: Arthur Pratt Grant/research support from: GSK, Pfizer Janssen, Andrew Mellor: John D Isaacs Speakers bureau: Abbvie, Gilead, Roche, UC, Consultant of: Pfizer, GSK Amy E. Anderson Janssen