OP0040 Synovial cell infiltration in acpa-ve patients displays similar signatures to other seronegative inflammatory arthritis. results from the pathobiology of early arthritis cohort (PEAC)
Authors: G. Lliso-Ribera, F. Humby, A. Nerviani, M.A. Boutet, S. Kelly, M. Bombardieri, M. Lewis, R. Hands, V. Rocher, F. Bene, C. Buckley, P.C. Taylor, I.B. McInnes, C. Pitzalis
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> There is increasing evidence to suggest that ACPA +ve and ACPA-ve RA are distinct diseases. Current data demonstrates overlap in classification criteria between ACPA-ve RA and other sero negative inflammatory arthritidies such as PsA. Associated with this is a variable prognosis and response to treatment for patients with ACPA-ve RA. Biomarkers capable of refining diagnosis and improving on current classification criteria early in the disease course for patients with ACPA-ve RA are thus urgently needed. Data examining the synovial pathophysiological relationship between PsA and ACPA ±RA is currently limited although has the potential to identify disease specific synovial cellular and molecular signatures. <h3>Objectives</h3> Therefore, the aim of this study is to examine in a cohort of therapy naïve, early inflammatory arthritis patients, whether ACPA-ve RA can be defined at disease initiation according to synovial pathobiological signatures. <h3>Methods</h3> A total of 186 consecutive DMARD naïve inflammatory arthritis patients (disease duration &lt;1 year) recruited as part of the multicentre PEAC study at Barts Health NHS Trust were evaluated. All patients underwent a baseline synovial biopsy of a clinically active joint along with collection of inflammatory markers (CRP). Following H and E staining, sections underwent immumohistochemical staining and semi-quantitative scoring (0–4) to determine the degree of CD20 +Bcells, CD3 +T cells, CD68 +lining (l) and sublining (sl) macrophage and CD138 +plasma cell infiltration. Sections were categorised into three pathotypes: (i) Fibroid(F):(CD68 SL &lt;2 and or CD3, CD20, CD138 &lt;1), (ii) Myeloid(M):(CD68SL &gt;2, CD20 &lt;1 and or CD3 &gt;1) and (iii) Lymphoid(L):(grade 2–3 CD20 +aggregates, CD20 &gt;2). <h3>Results</h3> 90/186 patients were classified as ACPA+ve RA, 55/186 as ACPA-ve RA and 41/186 as PsA. 80% of synovial samples were collected from small joints (wrist, MCP, PIP). All 186 samples were suitable for analysis. Results confirmed that C-reactive protein (CRP) as inflammatory marker does not differentiate between subgroups (p 0.41). Significantly higher degree of immune cell infiltration was seen between ACPA+ve vs ACPA-ve and ACPA+ve vs PsA but not between ACPA-ve and PsA (figure 1). When grouping patient between clinical subgroups (ACPA+ve vs ACPA-ve vs PsA) and pathotypes (fibroid, myeloid and lymphoid) (table1) we demonstrated a significantly higher prevalence of a lymphoid pathotype in ACPA+ve RA vs ACPA-ve or PsA. <h3>Conclusions</h3> Our results suggest that the synovial cell infiltrate (B cells, T cells, macrophages and plasma cells) in ACPA-ve RA is significantly different from ACPA +ve patients. They also suggest shared pathophysiological mechanisms between PsA and ACPA-ve RA and support a role for future refinement of diagnosis of ACPA-ve RA according to synovial pathobiology. <h3>Disclosure of Interest</h3> None declared