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A Decreased Absolute Number of Treg Cells in Patients with Active Rheumatoid Arthritis is Associated with Elevated Serum Osteopontin Levels with Disease Progression

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Abstract

Introduction

Rheumatoid arthritis (RA) is a chronic and refractory autoimmune disease characterized by synovial inflammation with unknown aetiology. Immune system dysfunction mediated by CD4+ T lymphocytes, which is regulated by the cytokine osteopontin (OPN), plays an important role in the pathogenesis of RA.

Methods

In this study, the levels of peripheral CD4+ T subsets and serum OPN in patients with active RA were measured and analysed to determine the possible pathogenesis of RA and to provide potential therapeutic targets.

Results

Serum OPN levels in both patients with active RA and patients with refractory RA were higher than those in healthy controls (HCs). Compared with HCs, the absolute numbers of Th2 cells increased in patients with active RA, while the absolute counts of Th1 and Treg cells decreased. There was no significant difference in CD4+ T subset levels between new-onset and refractory patients. As the condition persisted or deteriorated, a gradual increase in the levels of OPN and gradual declines in the absolute counts of Th1 and Treg cells were observed in patients with active RA. The fewest Th1 and Treg cells and the highest OPN levels were observed in patients with high disease activity. The serum OPN level was only significantly negatively correlated with the absolute counts of Treg cells in the CD4+ T lymphocyte subsets.

Conclusions

Fewer Treg cells with the increase in disease activity may be related to the increased OPN concentration, which may provide new ideas and directions for the targeted immunoregulatory treatment of RA.

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Acknowledgements

Funding

This work was supported by the Key Research and Development Program of Shanxi Province (No. 201803D31127), funded the study. The journal’s Rapid Service and Open Access Fees was funded by the authors.

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

Study design and manuscript writing: JX and JW. Data extraction, quality assessment, analysis and interpretation of data: JH, RJ, XW and HB. All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Li had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Disclosures

All authors declare no personal, financial, commercial or academic conflict of interest. Jian-Fang Xie, Jia Wang, Huan-Huan Bai, Jiao-Jiao He, Rui-Huan Jia, Xia Wang, Wen-Qi Zhang, Xiang-Cong Zhao, Xian-Cheng Zhang, Guang-Ying Liu, and Xiao-Feng Li all have nothing to disclose.

Compliance with Ethics Guidelines

This study was approved by the institutional review board of the Second Hospital of Shanxi Medical University (2016 KY-007). The study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments. This was an retrospective study using data which was anonymous, thus patient consent was not required.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Author notes

  1. Jian-Fang Xie and Jia Wang contributed to the work equally and should be regarded as co-first authors.

Authors and Affiliations

  1. Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China

    Jian-Fang Xie, Jia Wang, Huan-Huan Bai, Jiao-Jiao He, Rui-Huan Jia, Xia Wang, Wen-Qi Zhang, Xiang-Cong Zhao, Xian-Cheng Zhang, Guang-Ying Liu & Xiao-Feng Li

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  1. Jian-Fang Xie
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Correspondence to Xiao-Feng Li.

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Xie, JF., Wang, J., Bai, HH. et al. A Decreased Absolute Number of Treg Cells in Patients with Active Rheumatoid Arthritis is Associated with Elevated Serum Osteopontin Levels with Disease Progression. Adv Ther 39, 3280–3291 (2022). https://doi.org/10.1007/s12325-022-02171-9

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  • DOI: https://doi.org/10.1007/s12325-022-02171-9

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