OP0113 HISTOLOGICAL AND MOLECULAR PORTRAIT OF THE SYNOVIAL TISSUE IN EARLY TREATMENT-NAÏVE PSORIATIC ARTHRITIS IN COMPARISON WITH RHEUMATOID ARTHRITIS

Background Psoriatic Arthritis (PsA) and Rheumatoid Arthritis (RA) are autoimmune joint diseases characterised by chronic inflammation of the synovial tissue (ST). It has been previously suggested that PsA-ST has less marked hyperplasia of the synovial lining and fewer infiltrating T/B cells in comparison with RA. However, several confounders such as treatment, disease duration, sampling techniques and predominance of large joints samples may have influenced these findings. Objectives To compare the synovial features of PsA/RA at the beginning of the disease process and prior to any treatment for defining their histological/molecular individual characteristics, and to correlate the histological pattern with clinical parameters. Methods 183 consecutive treatment-naïve patients with <12 months symptoms and active synovitis of at least one joint were enrolled into the Pathobiology of Early Arthritis Cohort (PEAC) at the Barts Health NHS Trust, and underwent a baseline US-guided synovial biopsy of an inflamed joint. ST inflammatory infiltrate was evaluated by semi-quantitative score (0-4) of the immunostaining for CD68 (macrophages), CD3 (T cells), CD20 (B cells) and CD138 (plasma cells). Patients were classified as: pauci-immune if CD68sublining (SL)<2 and/or CD3-CD20-CD138<1; diffuse-myeloid if CD68SL≥2, CD20<2 or CD138<2; lymphoid-myeloid if CD20≥2 or CD138>2. RNA sequencing of the ST was performed on 93RA/15PsA patients. Results 39/183 patients were diagnosed with PsA (32 polyarticular, 7 oligoarticular) and 144/183 with RA (2010 ACR/EULAR criteria). Age was significantly lower in PsA patients. The comparison of the age-adjusted baseline variables showed: significantly higher number of tender and swollen joints in RA, but no significant differences between ESR, CRP and DAS28; higher US synovial thickening score of the biopsied joint in PsA, but comparable power-doppler. ST was obtained from small joints in 74.4% of PsA and 82% of RA. Histological comparison is summarised in Table 1 and 2. Only in RA, the pauci-immune pathotype associated with significantly lower ESR, CRP and DAS28 compared to lymphoid-myeloid; this association was maintained in a subset of 26 RA patients age- and gender-matched with the PsA population. Transcriptomic profiling showed that PsA-ST has significantly higher expression of the skin fibroblasts, eosinophils and neutrophils cellular gene modules. Genes significantly up regulated in PsA clustered in neutrophil recruitment/enrichment, cell migration and cytoskeleton remodelling modules. PsA(n=37) RA(n=125) p value CD3 0.9 (1) 1.7 (1.3) 0.0045* CD20 0.8 (1.1) 1.4 (1.5) 0.03* CD68L 1.5 (1.3) 1.8 (1.2) 0.16 CD68SL 1.8 (1.2) 2.3 (1.2) 0.04* CD138 0.8 (1.2) 1.4 (1.5) 0.02* PsA(n=37) RA(n=125) p value Pauci-immune 16 (43.2%) 31 (24.8%) 0.056 Diffuse-Myeloid 12 (32.4%) 40 (32%) Lymphoid-Myeloid 9 (24.4%) 54 (43.2%) Conclusion The identification of specific histological and molecular signatures characterising early-untreated PsA will help to better understand the disease pathogenesis and explore novel therapeutic targets. Reference [1] van Kuijk AW, Tak PP. Synovitis in psoriatic arthritis: immunohistochemistry, comparisons with rheumatoid arthritis, and effects of therapy. Curr Rheumatol Rep. 2011 Aug;13(4):353-9 Disclosure of Interests Alessandra Nerviani: None declared, Gloria Lliso Ribera: None declared, Marie Astrid Boutet: None declared, Katriona Goldmann: None declared, Stephen Kelly: None declared, Michele Bombardieri Grant/research support from: Celgene, Consultant for: Medimmune, Myles Lewis Grant/research support from: Celgene, Frances Humby: None declared, Costantino Pitzalis Grant/research support from: Celgene