Levels of Circulating Th17 Cells and Regulatory T Cells in Ankylosing Spondylitis Patients with an Inadequate Response to Anti-TNF-α Therapy

Purpose To investigate the effects of TNF-alpha blockage on levels of circulating Th17, Treg and their related cytokines in ankylosing spondylitis (AS) patients with different response to anti-TNF-alpha therapy. Methods The frequencies of circulating Th17 and Treg and serum levels of related cytokines were determined using flow cytometry analysis and ELISA, respectively, in 222 AS patients both before (baseline) and 6 months after anti-TNF-alpha therapy. Therapeutic response was defined according to ASAS (Assessment in Spondyloarthritis International Society) response criteria. Results Significantly higher baseline circulating Th17 and serum TNF-alpha, IL-6, IL-17, IL-23 were observed in active AS patients than in healthy controls. After anti-TNF-alpha therapy, 168 patients (75.7 %) were responders and 54 (24.3 %) were non-responders. Frequencies of Th17 significantly decreased in responders, but significantly increased in non-responders. Treg increased significantly in responders but decreased significantly in non-responders. Levels of TNF-alpha, IL-6, IL-17, and IL-23 were significantly decreased in responders. In contrast, IL-17 and IL-23 significantly increased in non-responders. TGF-beta were significantly increased only in responders, whereas no significant changes were seen in IL-10 in either responders or non-responders. Spearman correlation analysis showed that frequencies of Th17 and levels of TNF-alpha, IL-6, IL-17, and IL-23 were positively correlated with BASDAI score. They were also positively correlated with BASFI score except for IL-6. Treg were found to be negatively correlated with BASDAI score. Conclusions The beneficial effect of anti-TNF-alpha therapy in AS might not only neutralize the effects of TNF-alpha but also down-regulate Th17 and Th17-related cytokines accompanied by up-regulating the Treg/TGF-beta axis in responders.