Peripheral Treg Levels and Transforming Growth Factor-β (TGFβ) in Patients with Psoriatic Arthritis: A Systematic Review Meta-Analysis

Abstract

Introduction: Studies on the level of regulatory T (T_reg) cells in psoriatic arthritis (PsA) have been controversial, leading to disagreement regarding the role T_reg cells play in the pathogenesis of the disease. To clarify the status of T_reg cells in patients with PsA, we performed a meta-analysis to determine the levels of T_reg cells and serum T_reg-associated cytokines in PsA patients.

Methods: According to published data from PubMed, Web of Science, Embase, Clinical Trials.gov, MEDLINE, Web of Knowledge, Cochrane Library, and FDA.gov, we determined the T_reg and T_reg cytokine levels in patients with PsA. The effect estimates were pooled using a random-effects model.

Results: This meta-analysis included 12 studies. Compared to healthy controls (HCs), the proportions of T_reg cells had no significant difference in patients with PsA (based on standardized means[SMD] = - 1.038, 95% confidence intervals[CI] = - 2.165 to 0.089, p = 0.071). On the basis of subgroup analysis, patients with PsA had a lower percentage of CD4⁺ T_reg cells (SMD = - 1.501, 95% CI - 2.799 to - 0.202, p = 0.023) than OKT8⁺ T_reg (SMD = 0.568, 95% CI - 2.127 to 3.263, p = 0.679). Besides, CD4⁺CD25⁺FoxP3⁺ T_reg cells and CD4⁺CD25^highCD127^low T_reg cells were both significantly decreased on the levels of PBMCs in patients with PsA (SMD = - 0.764, 95% CI - 1.404 to - 0.125, p = 0.019; SMD = - 5.184, 95% CI - 6.955 to - 3.412, p < 0.001). CD4⁺CD25⁺FoxP3⁺ T_reg cells were particularly more abundant in the synovial fluid thanin peripheral blood (SMD = 3.288, 95% CI 2.127 to 4.449, p < 0.001). No significant difference was observed in the proportion of CD4⁺CD25⁺ T_reg cells in peripheral blood and CD4⁺CD25⁺FoxP3⁺ T_reg cells in CD4⁺ T cells (SMD = - 2.498, 95% CI - 7.720 to 2.725, p = 0.349; SMD = - 0.719, 95% CI - 2.525 to 1.086, p = 0.435). PsA patients had decreased cytokines such as transforming growth factor-β (TGFβ) (SMD = - 2.199, 95% CI - 3.650 to - 0.749, p = 0.003).

Conclusions: T_reg definition markers influence the scale of T_reg cells in patients with PsA. Pathogenesis of PsA may be attributed to an insufficient or malfunctioning T_reg population.

Keywords: Psoriatic arthritis; TGFβ; Treg.