O20 Histological and molecular features of the diseased synovium in early untreated PsA in comparison with RA
Authors: Nerviani Alessandra , Lliso-Ribera Gloria , Boutet Marie-Astrid , Goldmann Katriona , Rivellese Felice , Kelly Stephen , Bombardieri Michele , Lewis Myles , Humby Frances , Pitzalis Costantino 
Published: April 2020

Abstract

Background
Psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are clinically distinct autoimmune joint disorders both marked by the chronic infiltration of the synovial tissue (ST) by inflammatory cells. It has been proposed that a more prominent thickening of the lining layer and a higher number of T/B-cells within the sublining characterised RA-ST. However, in most studies, patients had established disease and were already exposed to treatments. Furthermore, a prevalent number of samples from large joints may have affected these conclusions. Here, we intended to portrait the histological and molecular characteristics of the PsA-ST before any therapeutic modulation and early in the disease in comparison with RA and correlate them with the clinical features.

Methods
183 consecutive patients naïve to DMARDs/steroids with ongoing symptoms for less than 12 months and at least one inflamed joint entered the Pathobiology of Early Arthritis Cohort (PEAC) at the Barts Health NHS Trust and underwent a US-guided synovial biopsy. ST was immuno-stained for CD3-CD20-CD138-CD68 to quantify the cellular infiltrate by T-cells, B-cells, plasma cells and macrophages, respectively. Based on the semi-quantitative score (0-4) of the immune markers, patients were categorised in lympho-myeloid (CD20≥2 or CD138&gt;2), diffuse-myeloid (CD68 sublining≥2, CD20 and CD138&lt;2) and pauci-immune (CD68sublining&lt;2 and/or CD3-CD20-CD138&lt;1). Molecular analysis was performed using RNA-sequencing of 93 RA and 15 PsA-ST. RNA cellular content was quantified using Fantom5-gene-modules.

Results
Of 183 patients, 39 were diagnosed with PsA (32 polyarticular, 7 oligoarticular) and 144 with RA (2010 ACR/EULAR criteria). Age was significantly lower in PsA patients. Small joints were biopsied in 74.4% of PsA and 82% of RA patients. US-synovial thickening score of the biopsied joint was, on average, higher in PsA while the power-doppler signal was similar. The histological comparison proved fewer infiltrating T/B-cells, plasma cells and sublining macrophages in PsA than RA, yet a comparable macrophage composition of the lining. The pathotypes' distribution was different, with prevalent pauci-immune in PsA (43.2%) and lympho-myeloid in RA (43.2%). At baseline, the number of tender/swollen joints was significantly higher in RA, while there were no differences in other clinical parameters such as DAS28. In PsA, synovial pathotypes did not define clinical phenotypes, whereas RA pauci-immune patients had less severe disease activity than lympho-myeloid; this relation was confirmed in an age/gender-matched to PsA subset of 26 RA subjects. The molecular profiling revealed that PsA-ST composition had a greater content of fibroblasts, eosinophils and neutrophils. Moreover, PsA-ST had higher expression of neutrophil recruitment/enrichment, cell migration and cytoskeleton remodelling gene-modules clusters.

Conclusion
Discovering distinct synovial tissue signatures characterising early treatment-naive PsA will provide a better understanding of the disease pathogenesis and suggest innovative therapeutic targets.

Disclosures
A. Nerviani None. G. Lliso-Ribera None. M. Boutet None. K. Goldmann None. F. Rivellese None. S. Kelly None. M. Bombardieri None. M. Lewis None. F. Humby None. C. Pitzalis None.