Decreased circulating follicular regulatory T cells in patients with dilated cardiomyopathy.

Xixi Liu,Wencai Zhang,Zhanying Han

doi:10.1590/1414-431x2021e11232

Abstract

Follicular regulatory T cells (Tfr) have critical functions in inflammatory and autoimmune disorders. The main purpose of the current work was to assess Tfr cell frequency in patients with dilated cardiomyopathy (DCM). Flow cytometry showed that, compared with normal controls, DCM cases showed markedly reduced Tfr cell rates and Tfr/Tfh ratios, but significantly increased follicular helper T cell (Tfh) rates. Correlation analysis showed that the Tfr rate in DCM patients was positively correlated with left ventricular ejection fraction (LVEF), and negatively correlated with N-terminal brain natriuretic peptide (NT-proBNP) levels. Lower Foxp3 and higher Bcl-6, ICOS, and PD-1 mRNA expression levels were found in patients with DCM. In addition, plasma interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-21 levels were significantly increased in DCM cases. Moreover, IgG and IgG3 levels were also elevated in individuals with DCM. Correlation analysis showed that the Tfr rate in DCM patients was negatively correlated with IgG and IgG3, while the Tfh rate was positively correlated with IgG and IgG3. Changes in circulating Tfr levels may have a critical immunomodulatory function in DCM and may become a new therapeutic target for DCM.

Highlights

Dilated cardiomyopathy (DCM) is a heterogeneous cardiomyopathy with unknown etiology and progressive characteristics, mainly featuring an enlarged chamber and impaired systolic function in at least one ventricle [1]
In the DCM group, diuretics, cardiotonic drugs, b-receptor blockers, angiotensin receptor enkephalinase inhibitors (ARNI), angiotensin-converting enzyme inhibitors (ACEI), and/or angiotensin receptor blockers (ARB) were utilized at higher frequencies compared with the healthy control group
In order to further evaluate the possible role of Tfr changes in DCM, we analyzed the associations of Tfr and Tfh cell frequencies with cardiac function indexes in DCM patients

Summary

Introduction

Dilated cardiomyopathy (DCM) is a heterogeneous cardiomyopathy with unknown etiology and progressive characteristics, mainly featuring an enlarged chamber and impaired systolic function in at least one ventricle [1]. Multiple reports revealed that immunological factors have critical functions in patients with DCM, and have demonstrated that abnormal autoimmune reactions cause impaired activation of humoral and cellular immunity, thereby participating in the development of DCM [3,4]. Activation markers, such as CD69, CD25, HLA-DR, and CD40 ligand, on the surface of T lymphocytes are significantly increased in DCM patients [5]. Cytokines, including interleukin (IL)-6 and tumor necrosis factor (TNF)-a, are significantly elevated in DCM and show negative correlations with heart function [7]. Anti-myocardial autoantibodies, anti-mitochondrial antibodies, and anti-b1Rs antibodies all have essential functions in DCM development, diagnosis, and treatment [8,9]

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