Role of synovial fibroblast subsets across synovial pathotypes in rheumatoid arthritis: a deconvolution analysis

• DOI: 10.1136/rmdopen-2021-001949
• Publication Date: 2022-01-05T16:45:19Z
• Authors: Raphael Micheroli; Muriel Elhai; Sam Edalat; Mojca Frank-Berto...; Kristina Bürki; Adrian Ciurea; Lucy MacDonald; Mariola Kurowska-...; Myles J Lewis; Katriona Goldmann; Cankut Cubuk; Tadeja Kuret; Oliver Distler; Costantino Pitzalis; Caroline Ospelt
• Keywords: 0301 basic medicine; 2403 Immunology; rheumatoid; 2745 Rheumatology; Synovial Membrane; 10051 Rheumatology Clinic and Institute of Physical Medicine; 610 Medicine & health; Rheumatoid Arthritis; Fibroblasts; Arthritis, Rheumatoid; 03 medical and health sciences; arthritis; fibroblasts; 2723 Immunology and Allergy; Humans; synovitis

To integrate published single-cell RNA sequencing (scRNA-seq) data and assess the contribution of synovial fibroblast (SF) subsets to pathotypes respective clinical characteristics in treatment-naïve early arthritis.In this silico study, we integrated scRNA-seq from studies with additional unpublished in-house data. Standard Seurat, Harmony Liger workflow was performed for integration differential gene expression analysis. We estimated single cell type proportions bulk RNA-seq (deconvolution) tissue 87 arthritis patients Pathobiology Early Arthritis Cohort using MuSiC. SF across (fibroid, lymphoid myeloid) relationship disease activity measurements different were assessed.We identified four clusters marker genes: PRG4+ (CD55, MMP3, PRG4, THY1neg ); CXCL12+ (CXCL12, CCL2, ADAMTS1, THY1low POSTN+ (POSTN, collagen genes, THY1); CXCL14+ (CXCL14, C3, CD34, ASPN, THY1) that correspond lining (PRG4+ SF) sublining (CXCL12+ SF, + subsets. most prominent fibroid while appeared highest myeloid pathotype. Corresponding, assessed by histology (assessed Krenn-Score) thicker myeloid, but also pathotype correlated positively severity parameters fibroid, whereas showed negative association all pathotypes.This study shows a so far unexplored between distinct pathologies subtypes defined scRNA-seq. The knowledge diverse interplay immune cells will advance opportunities tailored targeted treatments.