Interleukin-22 and T-helper-22 Cells in Patients with Enthesitis-related Arthritis

Background: Animal models studies show the role of interleukin-22 (IL-22) in the pathogenesis of enthesitis. We analysed an association of IL-22 levels with enthesitis in Enthesitis-related juvenile idiopathic arthritis (JIA-ERA) patients. Methods: Patients with JIA-ERA, polyarticular JIA (Poly-JIA), and healthy controls (HC) were enrolled. The frequencies of Th1, Th17 and Th22 cells in peripheral blood (PB) and synovial fluid (SF) were determined by flow cytometry, and IL-22 levels in SF by ELISA. Data is shown as median with interquartile range. Results: T-cell frequency was determined in 40 JIA-ERA (33 boys, 16 [3.3] years), 10 Poly-JIA (3 boys, 14.5 [6] years), and 10 HC (9 boys, 18 [2] years). Among 40 JIA-ERA patients, 28 had enthesitis. In JIA-ERA, Th1 cell frequency was significantly higher in SF (8.6 [4.5]) than in PB (2.9 [0.55]; P = 0.007). Th22 cell frequency in PB was higher in active JIA-ERA patients as (0.2 [0.1]; JSpADA >2.5) compared to the inactive disease (0.15 [0.18]; P = 0.02). No association was observed between Th22 cell frequency and enthesitis. No difference in serum IL-22 levels of 85 JIA-ERA (78 boys, 16 [4] years), 13 Poly-JIA (4 boys, 12 [7.5] years), and 31 HC (27 boys, 25 [8] years) was observed. SF showed higher IL-22 levels than corresponding serum samples (P = 0.04). Conclusion: High SF levels of IL-22 suggests its role in inflammation in JIA-ERA patients. The lack of association of PB Th22 cell frequency with enthesitis suggests that immune abnormalities at local site may not be reflected in PB.