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)

• Published in: Annals of the rheumatic diseases Vol. 77; no. Suppl 2; p. 71
• Main Authors: Lliso-Ribera, G., Humby, F., Nerviani, A., Boutet, M.A., Kelly, S., Bombardieri, M., Lewis, M., Hands, R., Rocher, V., Bene, F., Buckley, C., Taylor, P.C., McInnes, I.B., Pitzalis, C.
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2018
• Subjects: Arthritis; Biopsy; C-reactive protein; CD20 antigen; CD3 antigen; Diagnosis; Fibroids; Joint diseases; Lymphocytes B; Lymphocytes T; Macrophages; Patients; Plasma cells; Wrist
• DOI: 10.1136/annrheumdis-2018-eular.3489
• ISSN: 0003-4967

BackgroundThere 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.ObjectivesTherefore, 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.MethodsA total of 186 consecutive DMARD naïve inflammatory arthritis patients (disease duration <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 <2 and or CD3, CD20, CD138 <1), (ii) Myeloid(M):(CD68SL >2, CD20 <1 and or CD3 >1) and (iii) Lymphoid(L):(grade 2–3 CD20 +aggregates, CD20 >2).Results90/186 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.RA acpa +N909ungradedRA acpa-N5512ungradedPsAN410ungradedP value fisher testP value acpa+vs acpa-P value acpa+vs PsAP value acpa- vs PsA F 15 (16%)17 (31%)15 (36%)0.01*0.03*0.005*0.41M 25 (28%)14 (25%)11 (27%)L 41 (45%)12 (22%)10 (24%)ConclusionsOur 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.Disclosure of InterestNone declared