Proportion of T follicular helper cells in peripheral blood of rheumatoid arthritis patients: a systematic review and meta-analysis

ABSTRACT

Introduction:Alterations in the levels and activity of Tfh may lead to impaired immune tolerance and autoimmune diseases. The aim of this study was to investigate the proportion and types of Tfh cells in the peripheral blood (PB) of RA patients.

Areas covered:Comprehensive databases were searched for studies evaluating the proportion of Tfh cells in the PB of patients with RA compared to healthy control (HCs).

The proportion of Tfh cells in RA patients was significantly higher than in HCs (SMD 0.699, [0.513, 0.884], p < 0.0001). Furthermore, Tfh cells proportion in untreated-RA and early-RA patients was markedly greater than HCs, when comparisons done without considering the definition markers, and also when Tfh cells were defined by the specified definition markers. While the proportion of Tfh cells by all definitions was higher in active-RA compared to HCs, analysis of two definitions, CD4⁺CXCR5⁺ and CD4⁺CXCR5⁺ICOS⁺, didn’t show significant differences. Furthermore, higher proportion of Tfh cells defined by all definitions and a specified definition (CD4⁺CXCR5⁺PD-1^high) was observed when S⁺RA compared to S⁻RA patients.

Expert opinion:The results demonstrate that circulating Tfh are highly elevated in RA patients highlights its potential use as a biomarker and a target for RA therapy.

KEYWORDS:

• T follicular helper cells
• tfh
• rheumatoid arthritis
• systematic review
• meta-analysis

Article highlights

• The proportion of Tfh cells defined by all definition markers was higher in PB of RA patients than HCs.

• The proportion of Tfh cells with individual definitions were higher in PB of RA patients than in HCs.

• Tfh cells proportion in untreated-RA and early-RA patients was greater than HCs.

• The proportion of Tfh cells defined by all definitions was higher in active – RA compared with HCs.

• Seropositive RA patients had higher Tfh cells proportion compared to seronegative patients.

• These results highlight potential pathogenic role of Tfh cells in RA and its potential use as a biomarker and a target for RA therapy.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

PB: conception and design. PB, MAH and KK: data collection. PB: statistical analysis and interpretation of the data. PB: paper writing. KK, KKE, RES, DK, SM: paper review & editing. All authors approved the submitted version of the manuscript.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This study was supported by Isfahan University of Medical Sciences (No 54795).