Objectives: This study determines the phenotypic and functional characteristics that define distinct fibroblast-like synoviocyte (FLS) populations in rheumatoid arthritis (RA) vs psoriatic arthritis (PsA).Methods: Single-cell RNA sequencing and multiparametric flow cytometry analysis (21 markers) were performed on RA and PsA synovial cell suspensions to determine FLS phenotype/function.Podoplanin (PDPN) + FLS and sorted THY1 + FLS vs THY1 FLS function in RA vs PsA was assessed by flow cytometry, enzyme-linked immunosorbent assay (ELISA), quantitative real -time quantitative polymerase chain reaction (qPCR), and metabolic analysis ex vivo, in vitro, and in the presence of verteporfin (Hippo signalling blockade).Results: Flow analysis of PDPN + FLS demonstrated significant increases in human leukocyte antigen (HLA)-DR + , yes-associated protein (YAP) + , cadherin 11 (Cad11) + , and phosphorylated protein S6 + FLS in RA (all P < .05),while CD55 was increased in PsA-FLS (P < .001).Polyfunctionality demonstrated enhanced coexpression of Cad11 + CD44 + HLA-DR + ICAM-1 + FLS (P < .01)and CD44 + HLA-DR + ICAM-1 + VCAM-1 + FLS (P < .05) in RA, whereas PsA-FLS exhibited increased coexpression of pAKT + pmTOR + (P < .01).THY1 + FLS populations were dominant in RA (P < .05),while THY1 FLS were dominant in PsA (P < .05),with differential angiogenic, chemokine, and matrix metalloproteinase expression observed.THY1 + FAP + FLS correlated with disease activity score (DAS28) (r = 0.55, P < .05)and synovitis (r = 0.54, P < .05).Further flow analysis identified 6 main distinct FLS populations, with enrichment of THY1 + CD34CD55FAP + FLS and THY1 + CD34 + CD55FAP + FLS in RA (P < .05),while PsA displayed enrichment of THY1 + CD34 -CD55 + FAP + FLS (P < .05)and THY1CD34CD55 + FAP + FLS (P < .001).Immune/adhesive markers were significantly higher in RA subpopulations, whereas metabolic/osteogenic markers were higher in PsA subpopulations.
Tynan et al. (2026) studied this question.