Decreased numbers and sex-based differences of circulating regulatory T cells in patients with seropositive undifferentiated arthritis

Abstract

Aims: CD4+ T cells play crucial roles as both mediators and regulators of the pathogenesis of rheumatoid arthritis (RA). However, the characteristics of CD4+ T cell subpopulations in the earliest stage of RA development remain unclear. Hence, we determined the proportions and absolute counts of circulating CD4+ T cell subsets in patients with seropositive undifferentiated arthritis (SUA), the early and preclinical stage of RA. Methods: Peripheral blood samples and clinical information were collected from 177 patients with SUA, 104 patients with RA, and 120 healthy controls. All patients were newly diagnosed and untreated. Proportions and absolute counts of CD4+ T cell subpopulations were determined by flow cytometric analysis. Results: In patients with SUA, percentages and absolute counts of circulating regulatory T (Treg) cells were decreased significantly and Th17/Treg cell ratios were abnormally increased, whereas Th17 cell numbers were similar to those in healthy controls. In addition, sex-based differences in circulating Treg cells were observed, with female SUA patients having lower proportions and absolute counts of Treg cells than those in males. Moreover, female patients with SUA had higher erythrocyte sedimentation rates and 28-joint Disease Activity Scores than those in males. Conclusion: Immune tolerance deficiency resulting from an abnormal reduction in circulating Treg cells might be the most crucial immunological event in the earliest stage of RA. The sex-specific disparity in Treg cells should also be considered for immunoregulatory and preventive strategies targeting early RA.

Characteristics of the Gut Microbiome and Its Relationship With Peripheral CD4+ T Cell Subpopulations and Cytokines in Rheumatoid Arthritis

“…After washing, the samples were analyzed by flow cytometry. The percentages and absolute counts of CD4 + T cell subpopulations were determined using BD Multitest software (BD Biosciences) (Niu et al, 2021).…”

Dose-dependent effects of oleuropein administration on regulatory T-cells in patients with rheumatoid arthritis: An in vitro approach

“…The substantial defect in the frequency of Tregs has previously been identified in RA patients. 13 , 14 , 53 However, the flow cytometry results showed no statistically significant difference in Treg frequencies between HC and RA patients, which might be related to the different effects of conventional and biological DMARDs on Tregs in RA patients. 54 – 57 A number of studies have shown that treatment of RA patients with some but not all of DMARDs, such as methotrexate, tumor necrosis factor-α inhibitors (TNF-αi), adalimumab, and etanercept can restore the regulatory functions of Tregs and increase the frequency of these cells through various mechanisms.…”

“… 2 , 4 , 10 – 12 In addition, a consistent number of studies have reported a decrease in the percentage of circulating Tregs in RA patients compared to healthy individuals. 13 , 14 Clinical treatment of RA, essentially involves the use of medications to improve disease progression and minimize disease activity. The majority of these medications have shown adverse effects.…”

Alterations in gut microbiota associated with lymphocyte subsets, cytokines, and disease activity in ankylosing spondylitis

“…BD TruCount tubes were used to determine the absolute counts of total CD4 + T cells in the peripheral blood. The absolute numbers of CD4 + T subsets (e.g., CD4 + Treg cells) were then calculated with the following calculation formula: Number of CD4 + T subsets = Number of CD4 + T cells × Percentage of CD4 + T subsets [24].…”