Abstract
Purpose
To investigate the effects of TNF-α blockage on levels of circulating Th17, Treg and their related cytokines in ankylosing spondylitis (AS) patients with different response to anti-TNF-α 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-α therapy. Therapeutic response was defined according to ASAS (Assessment in Spondyloarthritis International Society) response criteria.
Results
Significantly higher baseline circulating Th17 and serum TNF-α, IL-6, IL-17, IL-23 were observed in active AS patients than in healthy controls. After anti-TNF-α 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-α, 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-β 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-α, 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-α therapy in AS might not only neutralize the effects of TNF-α but also down-regulate Th17 and Th17-related cytokines accompanied by up-regulating the Treg/TGF-β axis in responders.
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Disclosure statement
Li Xueyi, Chen Lina and Wu Zhenbiao contributed equally to this work. Funding: This work was supported by grants from the Key Program of the National Natural Science Foundation of China (No. 81030058) and the National Basic Research Program (No. 2009CB521705). Ethics approval: The approval was granted from the Ethics Committee of the Fourth Military Medical University (No. 20080814–2). All patients and controls gave their informed consent to participate in the study.
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Xueyi, L., Lina, C., Zhenbiao, W. et al. Levels of Circulating Th17 Cells and Regulatory T Cells in Ankylosing Spondylitis Patients with an Inadequate Response to Anti−TNF-α Therapy. J Clin Immunol 33, 151–161 (2013). https://doi.org/10.1007/s10875-012-9774-0
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DOI: https://doi.org/10.1007/s10875-012-9774-0