POS0387 ACPA STATUS CORRELATES WITH DIFFERENTIAL IMMUNE PROFILE OF RHEUMATOID ARTHRITIS PATIENTS

Background: Rheumatoid arthritis (RA) is a progressive erosive autoimmune disease that affects 1% of the world population. Anti-citrullinated protein autoantibodies (ACPA) are routinely used for diagnosis RA, however 20-30% patients ACPA negative. status delineator RA endotypes with similar clinical manifestation but potentially different pathophysiology. Elucidating underlying mechanisms pathogenesis could inform treat to target approach both ACPA-positive and ACPA-negative patients. Objectives: To identify peripheral blood synovial tissue immune population differences associate endotype. unique patient gene signatures enriched pathways correlate status. Methods: Detailed high dimensionality flow cytometric analysis supervised unsupervised algorithm ACPApos ACPAneg single cell suspensions. Ex vivo T stimulation cytokine production characterisation. RNAseq specific pathway enrichment APCApos biopsies. Results: profiling based on key populations including B cells, follicular helper (Tfh) cells (Tph) CD4 proinflammatory responses revealed Tfh profiles. were characterised by significantly (*P=0.03) increased frequency (CXCR5 + ) distinct clustering influenced switched (IgD - CD27 DN memory compared APCAneg Surprisingly subpopulation distribution was between patients, significant accumulation double negative highlighting role subsets in endotypes. Interestingly, (TNF-α, IFN-γ, IL-2, GM-CSF, IL-17A, IL-22, IL-4) markedly hierarchical PCA revealing endotype profiles showing TNF-α (P=0.01) expression. receptor signalling Additionally, chemokine expression observed CXCR3 (P<0.001), CCR7 (P=0.002), CCR2 (P=0.004) decreased CXCR7 (P=0.007) Conclusion: associates profile immunological involved, therefore reinforcing need RA. Figure 1. biopsies related positive (n=50, performed DESq2 pathfindeR pipelines R ). Disclosure Interests: Achilleas Floudas: None declared, Mary Canavan: Trudy McGarry Employee of: Novartis, Vinod Krishna Janssen, Sunil Nagpal GSK, Douglas Veale Speakers bureau: Abbvie, MSD, Pfizer, UCB, Consultant Grant/research support from: Ursula Fearon UCB