Synovial cytokine expression in psoriatic arthritis and associations with lymphoid neogenesis and clinical features

Introduction: Psoriatic arthritis (PsA) is an autoantibody-negative immune-mediated disease in which synovial lymphoid neogenesis (LN) occurs. We determined whether LN is associated with specific patterns of inflammatory cytokine expression in paired synovial tissue (ST) and fluid (SF) samples and their potential correlation with the clinical characteristics of PsA. Methods: ST and paired SF samples were obtained from the inflamed knee of PsA patients. ST samples were immunostained with CD3 (T cell), CD20 (B cell), and MECA-79 (high endothelial vessels). Total ST mRNA was extracted, and the gene expression of 21 T-cell-derived and proinflammatory cytokines were measured with quantitative real-time PCR. SF concentrations of Th1, Th2, Th17, and proinflammatory cytokines were determined with the Quantibody Human Th17 Array. Clinical and biologic data were collected at inclusion and after a median of 27 months of follow-up. Results: Twenty (43.5%) of 46 patients had LN. Only two genes showed differences (Wilcoxon test, P < 0.06) in ST between LN-positive and LN-negative patients: interleukin-23A (IL-23A) (P = 0.058) and transforming growth factor-beta (TGF-beta 1) (P = 0.050). IL-23A expression was higher, and TGF-beta 1 expression was lower in LN-positive patients. ST IL-15 mRNA showed a nonsignificant trend toward higher expression in LN-positive patients, and SF IL-15 protein levels were significantly higher in LN-positive patients (P = 0.002). In all PsA patients, IL-23A mRNA expression correlated with C-reactive protein (CRP) (r = 0.471; P = 0.001) and swollen-joint count (SJC) (r = 0.350; P = 0.018), whereas SF levels of IL-6 and CC chemokine-ligand 20 (CCL-20) correlated with CRP levels (r = 0.377; P = 0.014 and r = 0.501; P < 0.0001, respectively). Conclusions: These findings suggest differences in the cytokine profile of PsA patients with LN, with a higher expression of IL-23A and IL-15 and a lower expression of TGF-beta 1. In the entire group of patients, IL-23 ST expression and CCL20 SF levels strongly correlated with markers of disease activity. This cytokine pattern was not accompanied by gross clinical or biologic differences between LN-positive and -negative patients. Taken together, these results suggest a role of the IL-17/IL-23 cytokine axis in synovial LN in PsA.