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Levels of Peripheral Th17 Cells and Th17-Related Cytokines in Patients with Ankylosing Spondylitis: A Meta-analysis

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Abstract

Background

Ankylosing spondylitis (AS) is a chronic inflammatory disease. Several proinflammatory cytokines produced by T helper 17 (Th17) cells are involved in the pathogenesis of AS. We performed a meta-analysis to determine the levels of Th17 cells and serum Th17-associated cytokines in patients with AS.

Methods

We determined the levels of Th17 cells and Th17 cytokines in patients with AS using data extracted from published articles retrieved from the PubMed, Embase, Web of Science, Cochrane Library, MEDLINE, Web of Knowledge, Clinical Trials.gov, and FDA.gov. databases. The effect estimates were pooled using a random-effects model. The review protocols were registered on PROSPERO (reference: CRD42021255741) and followed the PRISMA guideline.

Results

This meta-analysis included 138 studies. Compared to healthy controls (HCs), patients with AS had a higher proportion of Th17 cells (standardized mean difference [SMD] 2.23, 95% confidence interval [CI] 1.78–2.68; p < 0.001) and levels of proinflammatory cytokines, such as interleukin (IL)-17 (SMD 2.04, 95% CI 1.70–2.38; p < 0.001), IL-21 (SMD 1.77, 95% CI 0.95–2.59; p < 0.001), and IL-23 (SMD 1.11, 95% CI 0.78–1.44; p < 0.001). The subgroup analysis showed higher levels of IL-17+ Th17 cells among peripheral blood mononuclear cells (PBMCs) and CD4+ T cells in patients with AS compared to HCs (SMD 2.26, 95% CI 1.58–2.94 [p < 0.001] and SMD 1.61, 95% CI 0.55–2.67 [p = 0.003], respectively). Patients with AS had higher levels of CD4+IL-17+IFN-γ− Th17 in PBMCs and of CD4+CCR6+CCR4+Th17 in CD4+ T cells compared to HCs (SMD 1.85, 95% CI 1.06–2.64 [p < 0.001] and SMD 7.72, 95% CI 6.55–8.89 [p < 0.001], respectively). No significant differences were observed in the proportions of CD4+IL-17+IFN-γ− Th17 in CD4+ T cells and CD4+CCR6+CCR4+ Th17 in PBMCs (SMD − 0.11, 95% CI − 0.61 to 0.38 [p = 0.650] and SMD 1.32, 95% CI − 0.54 to 3.19 [p = 0.165], respectively). In addition, compared to stable AS, the levels of Th17 cells and IL-17 and IL-23 were significantly higher in active AS (SMD 1.58, 95% CI 0.30–2.85 [p = 0.016], SMD 3.52, 95% CI 0.72–6.33 [p = 0.014], and SMD 5.10, 95% CI 1.83–8.36 [p = 0.002], respectively).

Conclusions

The levels of Th17 cells and serum IL-17, IL-21, and IL-23 were higher in patients with AS than in HCs and, compared with stable AS, they increased more significantly in active AS. These results suggest that Th17 cells and Th17-related cytokines play major roles in AS pathogenesis and are an important target for treatment.

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Acknowledgements

An earlier version of this study was presented as a poster in 23rd Asia-Pacific League of Associations for Rheumatology (https://onlinelibrary.wiley.com/doi/10.1111/1756-185X.14200).

Funding

This work was supported by the National Natural Science Foundation of China (No. 82001740). The journal’s Rapid Service Fee was supported by The Second Hospital of Shanxi Medical University.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Author Contributions

QYS designed the study. JWZ and TYZ did the database search and selected the data. QYS and JYY analyzed the data. QYS and JWZ wrote the manuscript. SS, RZ, JKD, SXZ, CHW, HYG contributed to manuscript revision, read the revised manuscript, and approved the submitted version.

Disclosures

None of the the authors reports any conflict of interest, financial or otherwise. Qin-Yi Su, Jing-Wen Zheng, Jing-Yuan Yang, Tong-Yuan Zhang, Shan Song, Rong Zhao, Jing-Kai Di, Sheng-Xiao Zhang, Cai-Hong Wang and Hui-Ying Gao have nothing to disclose.

Compliance with Ethics Guidelines

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Data Availability

All data relevant to the study are included in the article or uploaded as online supplemental information. No additional data available.

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Authors and Affiliations

  1. Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China

    Qin-Yi Su, Shan Song, Rong Zhao, Sheng-Xiao Zhang, Cai-Hong Wang & Hui-Ying Gao

  2. Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Taiyuan, China

    Qin-Yi Su, Jing-Wen Zheng, Jing-Yuan Yang, Tong-Yuan Zhang, Shan Song, Rong Zhao, Jing-Kai Di, Sheng-Xiao Zhang, Cai-Hong Wang & Hui-Ying Gao

  3. Shanxi Provincial Key Laboratory of Rheumatism Immune Microecology, Taiyuan, Shanxi, China

    Qin-Yi Su, Shan Song, Rong Zhao, Sheng-Xiao Zhang, Cai-Hong Wang & Hui-Ying Gao

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Su, QY., Zheng, JW., Yang, JY. et al. Levels of Peripheral Th17 Cells and Th17-Related Cytokines in Patients with Ankylosing Spondylitis: A Meta-analysis. Adv Ther 39, 4423–4439 (2022). https://doi.org/10.1007/s12325-022-02240-z

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