Reduction of peripheral regulatory T cells in active rheumatoid arthritis patients with coronary artery disease

Yanyan Wang,Chong Gao,Caihong Wang,Xiaopu Yu,Rui Su,Xiaofeng Li,Fangyuan Hu,Mingxia Ma,Qiaoling Guo,Lizhi Wang,Baochen Li

doi:10.1186/s12865-021-00466-0

Abstract

ObjectiveTo identify lymphocyte and CD4 + T cell subset characteristics, particularly regulatory T cells (Tregs), in active rheumatoid arthritis (RA) patients with coronary artery disease (CAD).MethodsA total of 54 RA patients with CAD (RA-CAD group), 43 RA patients without CAD (pure RA group), and 43 healthy controls (HC group) were enrolled. The absolute number and frequency of lymphocyte subpopulations and CD4 + T cell subsets were analyzed by flow cytometry. Serum levels of cytokines were analyzed using a cytometric bead array. Clinical and laboratory data were collected retrospectively and their correlation with CD4 + T subsets were analyzed.ResultsThere was a significant decrease in the absolute number of Treg cells (CD4 + CD25 + Foxp3 + T cells) in the RA-CAD group compared to the pure RA group (p < 0.001). Similarly, both the absolute number (p = 0.001) and frequency (p = 0.011) of Tregs in the RA-CAD group were decreased compared to the HCs, causing a Th17/Treg imbalance (p = 0.044). No difference was found in the absolute number and frequency of Treg cells between the pure RA and HC groups. However, the absolute Th17 cell count was increased in the pure RA group (p = 0.032). The serum level of cytokine IL-17 was lower in the RA-CAD group than in the pure RA group (p = 0.023). In the RA-CAD group, the Treg number was negatively correlated with the RA disease activity score and ESR value, and LDL and ApoB100 levels were negatively correlated with the number of Th17 cells.ConclusionsActive RA patients with CAD sustain more severe immune tolerance damage and Th17/Treg disorder. Monitoring of lymphocyte and CD4 + T cell subsets, particularly Treg cells, is crucial to understanding immune status in this group. Focusing on RA activity and CAD risk control, immune-regulatory therapy based on the Treg level may be more beneficial for RA patients with CAD.

Highlights

Rheumatoid arthritis (RA) is a common immune-mediated inflammatory disease characterized by chronic synovitis and vasculitis
Based on analyses of the clinical factors correlated with combined RA-coronary artery disease (CAD) disease, which is different from pure RA disease, this study explored lymphocyte subsets, Treg cell characteristics, revealing the immune status of this group and thereby providing guidance on immune-based treatment
Serum levels of IgM and IgA were lower in the RA-CAD group than in the pure RA group; there were no significant differences in other assay indexes

Summary

Introduction

Rheumatoid arthritis (RA) is a common immune-mediated inflammatory disease characterized by chronic synovitis and vasculitis. Coronary artery disease (CAD) occurs more frequently as a manifestation of CVD in RA, and RA patients have higher levels of all types of coronary plaque, contributing to future adverse cardiac events [4]. This can be explained by the accumulation of classic risk factors for CAD, linked to the metabolic syndrome, and the systemic inflammatory load in RA [5]. Autoimmune disorders in RA patients induce activation of immune cells and the release of large amounts of inflammatory factors, which directly lead to vascular endothelial damage and platelet aggregation, accelerating the progression of atherosclerosis

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