Single-Cell and Spatial Omics Uncover Disease-Specific Synovial Landscapes in Rheumatoid and Psoriatic Arthritis.

Abstract

At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2025 annual meeting in Bogotá, Columbia, Alexandra Khmelevskaya and Dr. Christopher Ritchlin presented a basic symposium on synovial immunopathology. They presented a comparative analysis between rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Their multiomic studies revealed that RA is characterized by heightened intercellular signaling, particularly involving secreted phosphoprotein 1-positive (SPP1+) macrophages, chitinase-3-like protein 1-positive (CHI3L1+) fibroblasts, and fatty acid binding protein 5-positive inflammatory dendritic cell type 3 (FABP5+ iDC3]). Spatial transcriptomics confirmed direct, contact-dependent interactions between SPP1+ macrophages and iDC3 specifically in RA, whereas CHI3L1+ fibroblasts interacted with iDC3 through soluble mediators. Multiplex immunofluorescence validated the tissue localization of these subsets. In contrast, PsA was distinguished by transcriptionally activated CD8+ T cells in both synovium and peripheral blood, with open chromatin states indicating preactivation prior to tissue infiltration. These findings delineate RA-specific stromal-myeloid-dendritic cell networks and PsA-specific T-cell activation programs. Together, they underscore distinct immunopathogenic mechanisms and provide potential targets for precision therapeutics in inflammatory arthritis.