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.
Khmelevskaya et al. (Mon,) studied this question.