Clinical and Experimental Medicine

, Volume 19, Issue 1, pp 55–64 | Cite as

Imbalance of circulating Tfr/Tfh ratio in patients with rheumatoid arthritis

  • Xiuzhen Wang
  • Chunshu Yang
  • Feng Xu
  • Lin Qi
  • Jianing Wang
  • Pingting YangEmail author
Original Article


Follicular helper T(Tfh) cells and follicular regulatory T(Tfr) cells are critical for the development and maintenance of germinal center and humoral immune responses. Accumulating evidence has demonstrated that the dysregulation of either Tfh or Tfr cells contributes to the pathogenesis of autoimmune diseases. The aim of this study was to examine the numbers of Tfh and Tfr cells in patients with rheumatoid arthritis (RA). Twenty-four patients with RA patients and 20 health controls (HCs) were enrolled in this study. We analyzed the numbers of Tfh (CD4+ CXCR5+ PD-1hi) cells and Tfr (CD4+ CXCR5+CD127lo) cells in 24 RA patients via flow cytometry. The level of the soluble PD-1 and its ligands (sPD-L1 and sPDL-2) were examined by ELISA. Flow cytometry revealed that both circulating Tfh and Tfr cells were increased in RA patients compared with HCs. More importantly, the ratio of Tfr/Tfh was decreased, indicating a disruption of the balance between Tfh and Tfr. The Tfr/Tfh ratio was inversely correlated with level of serum CRP, ESR, RF, anti-CCP, IgG and DAS28 index. We also found that the serum level of sPD-1 was significantly elevated in the RA patients, which was positively correlated with CRP, ESR and the number of Tfh cells. These results indicate that an imbalance of circulating Tfr and Tfh cells may be involved in the immunopathogenesis of RA and may provide novel insight for the development of RA therapies.


Rheumatoid arthritis Follicular helper T cell(Tfh) Follicular regulatory T cell(Tfr) Tfr/Tfh PD-1 



Rheumatoid arthritis


Circulating follicular helper T


Circulating follicular regulatory T


Germinal center


Enzyme‐linked immunosorbent assay


C-reaction protein


Erythrocyte sedimentation rate


Immunoglobulin G


Rheumatoid factor


CXC chemokine receptor 5


Cyclic citrullinated peptide


Soluble PD-1


Soluble PD-L1


Soluble PD-L2


Disease activity score in 28 joints


Disease-modifying antirheumatic drug



This work was supported by the following grants: foundation from clinical medical research center of Shenyang City (18_009-4-03 to PT.Y.), foundation from the Major State Research Development Program of Liaoning, China (No. 2017225024 to PT.Y.), foundation from the Project for Construction of Major Discipline Platform in Universities of Liaoning province, China (2017001 to PT.Y.), the Program of the Distinguished Professor of Liaoning Province, Rheumatology (2017 to PT.Y.).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The studies have been approved by the ethics committee of the first affiliated hospital of China Medical University. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Rheumatology and ImmunologyFirst Affiliated Hospital, China Medical UniversityShenyangPeople’s Republic of China
  2. 2.Department of Rheumatology and ImmunologyFirst Affiliated Hospital, Jinzhou Medical UniversityJinzhouPeople’s Republic of China
  3. 3.Department of First Cancer InstituteFirst Affiliated Hospital, China Medical UniversityShenyangPeople’s Republic of China

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