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. 2013 Jan;33(1):151-61. doi: 10.1007/s10875-012-9774-0. Epub 2012 Aug 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antirheumatic Agents / therapeutic use
  • CD4 Lymphocyte Count
  • Cells, Cultured
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / therapeutic use
  • Male
  • Middle Aged
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Spondylitis, Ankylosing / blood
  • Spondylitis, Ankylosing / drug therapy*
  • Spondylitis, Ankylosing / immunology*
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology*
  • Th17 Cells / pathology
  • Time Factors
  • Treatment Failure
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / blood
  • Young Adult


  • Antirheumatic Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Etanercept