| Description: |
Background The mechanisms underlying the progression of chronic inflammatory arthritis remain largely unclear. Methods We used single-cell mass cytometry on peripheral blood from patients with active rheumatoid arthritis (RA; n=11), psoriatic arthritis (PsA; n=12), and controls (n=9) to identify circulating cells co-expressing mesenchymal markers, including the homotypic adhesion molecule cadherin-11 (CDH11), and chemokine receptors. Proteomic profiling was performed on matched plasma using Olink. Confocal microscopy was used to investigate cell localization in synovial tissue. Results Circulating cells co-expressing mesenchymal markers, including the adhesion molecule cadherin-11 (CDH11) and chemokine receptors, were identified. Of them, circulating fibroblasts (podoplanin + CD45 - CD3 - CD19 - CD4 - CD8 - CD56 - CD66b - CD294 - ) co-expressing CDH11 and C-C Chemokine Receptor 7 (CCR7) were found exclusively in arthritis patients’ blood. These cells were not detected in paired bone marrow samples, suggesting their potential origin from inflamed joints. Increased circulating fibrocytes (CD34 + HLA-DR + CD45 + CD3 - CD19 - CD4 - CD8 - CD56 - CD66b - CD294 - ) co-expressing CDH11 and CCR7 were also found in patients’ blood. These cells were more prevalent in bone marrow, supporting their bone marrow origin. Among various leukocyte subsets, CDH11 + CD90 + CCR6 + neutrophils were markedly elevated in both RA and PsA. These populations persisted after 3 months of antirheumatic drug administration, regardless of treatment response. Proteomic profiling on matched plasma using Olink, revealed that the presence of circulating CDH11 + fibroblasts was associated with higher C-X-C Motif Chemokine Ligand 1 (CXCL1), Angiopoietin 1 (ANGPT1) and Tissue Inhibitor of Metalloproteinase 3 (TIMP3) levels, proteins involved in angiogenesis, chemotaxis, and matrix remodeling, respectively. Moreover, in patients with detectable circulating CDH11 + fibroblasts chemokine signaling and cell-substrate adhesion were enriched. Finally, CDH11 ... |