LAUSR

Background: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are both characterized by significant heterogeneity in terms of clinical presentation and outcomes. Furthermore, RA and PsA may share some overlapping features such as autoantibody-negativity, polyarticular involvement, response to certain therapies and pattern of joint damage. The pathobiological bases underlying the intra-disease heterogeneity and the inter-disease similiarities between RA and PsA are however unkown. Objectives: Aim of the current study was to investigate the relationship between the synovial immune phenotype and different clinical subsets in patients with RA and PsA. Methods: The study population included 96 patients undergoing ultrasound-guided synovial biopsy of the knee and serum sampling on the same day. Patients were recruited according to defined clinical subtypes: anti-citrullinated positive (ACPA) RA (n=26), ACPA-negative RA (n=32), polyarticular (≥5 involved joints) PsA (n=15), and oligoarticular PsA (n=23). Patients were compared for: (i) demographic and clinical features; (ii) synovial histopathological characteristics including CD68-positive infiltrating macrophages, CD3-positive T lymphocytes, CD20-positive B lymphocytes (semi-quantitative scores 0-3); (iii) serum levels of the lymphoid chemokine CXCL13 as a marker of germinal centre activity. Results: Collectively, ACPA-positive RA patients, ACPA-negative RA patients and patients with polyarticular PsA presented comparable demographic and clinical features including gender distribution, age, number of involved joints and levels of acute phase reactants. Patients with oligoarticular PsA were instead younger, more frequently males, and with lower levels of acute phase reactants. The degree of macrophage and T cell infiltration correlated with the erythrocyte sedimentation rate (rho 0.38, p=0.001 and rho 0.24, p=0.04 respectively) and C-reactive protein levels (rho 0.38, p=0.001 and rho 0.28, p=0.01 respectively) irrespective of diagnosis, and was significantly lower in oligoarticular PsA (Figure 1 A, B). In contrast, the degree of B cell infiltration showed significant differences in relation to the disease subtype: the lowest levels were found in oligoarticular PsA, the highest levels in ACPA-positive RA, whilst ACPA-negative RA and polyarticular PsA presented with intermediate and comparable levels between the two extremes (Figure 1 C). Serum levels of CXCL13 correlated with the synovial B cell score (rho 0.30, p=0.03) and, similarly to synovial B cell infiltration, were differentially increased according to the clinical phenotype, with again similarities between ACPA-negative RA and polyarticular PsA (Figure 1 D).Figure 1. Conclusion: In patients with chronic inflammatory arthritis, synovial B cell infiltration and systemic markers of germinal centre activity are heterogeneously increased irrespective of disease diagnosis. ACPA-positive RA and oligoarticular PsA appear located at the extremes of a pathobiological continuum, whilst ACPA-negative RA and polyarticular PsA present with intermediate and comparable degrees of B cell involvement. Collectively, our findings open the interesting perspective of a tailored management of patients with inflammatory arthritis based on the disease pathotype rather than on clinical diagnosis. Disclosure of Interests: Ludovico De Stefano: None declared, Serena Bugatti Speakers bureau: Bristol-Myers Squibb, Sanofi, Lilly, Novartis, Pfizer, Abbvie, Silvia Rossi: None declared, Carlomaurizio Montecucco: None declared, Antonio Manzo Speakers bureau: Bristol-Myers Squibb, Abbvie, Pfizer