Background/Purpose: Rheumatoid arthritis (RA) is a progressive immune-mediated disease involving the synovitis that can culminate in joint destruction and early mortality.IL-17-producing T (Th17) cells and regulatory T (Treg) cells have been showed to play critical roles in the pathogenesis of RA. Osteopontin (OPN) is a matricellular protein that mediates diverse biological functions. OPN mediates cell migration, adhesion, and survival in many cell types. OPN also functions as a Th1 cytokine, promotes cell-mediated immune responses, and plays a role in chronic inflammatory and autoimmune diseases. Recently, studies revealed that OPN produced in RA SF was responsible for markedly increased Th17 and Both Treg-intrinsic and Treg-extrinsicis factors maintaining Bcl6 are important for controlling Treg cell stability. Recently, our studies have found that absolute number of CD4⁺CD25⁺Foxp3⁺ regulatory T cells (CD4⁺Tregs) was significantly decreased in peripheral blood from patients with RA as compared to that from normal controls. The purpose is to investigate the absolute number of Th17, CD4⁺CD25⁺Foxp3⁺ Treg cells as well as OPN content in peripheral blood of patients with RA and the correlation between OPN content with Th17 and Treg cells, to find a possible pathogenesis related to RA and new therapy for the RA treatment.

Methods: A total 67 of new-onset diagnosed patients with RA fulfilled the 2010 ACR/EULAR Classification Criteria of Rheumatoid Arthritis were enrolled and 93 healthy donors were used as control. The absolute number of peripheral CD4⁺Tregs cell was detected by multicolor flow cytometry . ELISA was used to detect OPN. Meanwhile, Test parameters were anti-cyclic citrullinated peptide antibody (Anti-CCP), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), rheumatoid factor(RF). At the same time, the DAS28 score of RA group was calculated.

Results: The levels of OPN in RA patients were increased significantly [(14.84±8.64) vs (10.59±3.40), P<0.001] and significantly positively correlated to ESR, DAS28 score, and RF (r=0.284, P=0.02; r=0.290, P=0.039; r=0.376, P=0.007). The absolute number of Treg cells was significantly decreased in RA patients as compared with the controls[(23.63±2.80) vs (33.67±26.83)ng/µl, P<0.001]. However, the absolute number of Treg cells was negatively to OPN levels, and the difference was statistically significant (r=-0.459, P=0.000). The absolute number of Th17 cells tends to reduce and there was no statistical significance[(7.64±6.44 ) vs (6.64±4.26) ng/µl, P=0.0129]. There is no significant correlation between OPN and Th17(r=0.006,P=0.963).

Conclusion: The levels of OPN in peripheral blood plasma in RA were significantly higher than in healthy group, OPN was positively correlated with the laboratory parameters of disease activity. There was a negative correlation between Treg cells and OPN in RA group, which suggested that the reduction of Treg cell levels may be associated with OPN concentration. The correlation of decreased CD4⁺Tregs and OPN may be involved in the pathogenesis of RA. Whether OPN lays a role in the reduction of Treg cells need to study further