OP0121 SYNOVIAL CELLULAR NICHES ARE DETERMINANTS OF ARTHRITIS PERSISTENCE VERSUS RESOLUTION IN EARLY UNTREATED ARTHRITIS

Background Published synovial research largely focuses on persistent clinical syndromes such as RA and PsA. However spontaneously resolving synovitis is a common manifestation of viral infection (parvovirus, influenza), post-bacterial reactive states metabolic disease gout. The study tissue taken from patients using advanced single cell methodologies may provide biomarkers outcome in early but also valuable resource to understand mechanisms underlying the subversion healthy resolution resulting disease. Objectives To use RNA sequencing cellular interactions governing versus persistence untreated with active arthritis. Methods Synovial biopsies were obtained ultrasound guidance treatment naïve Birmingham BEACON arthritis cohort presenting at least one clinically swollen joint amenable guided biopsy. Tissue samples who went develop (n=15) or PsA (n=7) according ACR criteria CASPAR 24month follow-up, whose resolved (n=5) underwent enzymatic disaggregation processed through multimodal single-cell approach including characterisation transcriptome 58 surface-protein-panel profile. Sequenced gene libraries integrated batch sample Harmony integrative algorithm before clustering annotating canonical marker genes. Seurat-based automated pipelines used for variable identification clustering. We DESeq2 identify per type genes, weighted co-expression network analysis (WGCNA) programmes associated (RA PSA) groups. NAMTI was unique niches resolution. Results ~90,000 viable cells sequenced data normalised, clustered annotated describing over 80 across eight main types (T, B, Plasma, Plasmacytoid DC, myeloid, fibroblast, mural vascular). A total 1945 genes varied significantly prognosis, distributed unequally (Table 1). Table 1. Cell T B Plasma DC Myeloid Fibroblast Mural Vascular Upregulated 43 300 0 4 378 270 11 153 persisting 37 82 3 1 205 223 7 228 Persistence (i) presence plasma se (ii) phenotypic shift vascular, Th, B-cell populations enrichment SPP1+ populations. Patients destined resolve exhibited Treg cells. Persistent characterised by significant compositional differences key lining sublining fibroblast subpopulations MMP3 positive cells, expression related matrix remodeling fibroblast:macrophage interactions. Conclusion spontaneous inflammation are accompanied characteristic mechanistic signatures that can be observed during inflammation. There potential exploit aim disrupting REFERENCES: NIL. Acknowledgements: Disclosure Interests Andrew Filer Consultant of: Janssen, Sonoma, Grant/research support from: BMS, Roche, UCB, Nascient, Mestag, GSK, Jason D. Turner: None declared, Cesar Prada-Medina: Moustafa Attar: Christopher D Buckley: Stephen Sansom: Karim Raza Abbvie Sanofi, Bristol Myers Squibb.