Regulatory T-cells and their impacts on cytokine profile of end-stage renal disease patients suffering from systemic lupus erythematosus

Abstract

Autoimmunity is an identified factor for development of end-stage renal disease (ESRD). Regulatory T-cells (Tregs) play a fundamental role in preventing autoimmunity. This study aimed to determine Treg frequency and its effects on cytokine profile of ESRD patients with and without systemic lupus erythematosus (SLE). Moreover, this study also determines how Treg number is affected by blood transfusion and gender. Peripheral blood mononuclear cells were isolated from 26 ESRD and 10 healthy subjects and stained with anti-CD4, anti-CD25, and anti-FoxP3 antibodies. Treg frequencies in ESRD patients with and without blood transfusion were determined by flow cytometry. Antibodies against human leukocyte antigens (HLAs) were investigated by panel-reactive antibodies screening. Tumor growth factor (TGF)-beta 1, interleukin (IL)-4, IL-10, TNF-alpha, IL-17A, and interferon (IFN)-gamma serum levels in participants were measured by enzyme-linked immunoasorbent assay (ELISA). ESRD patients with SLE, unlike the patients without SLE, showed a significant reduction in Treg percentage compared to healthy subjects (P < 0.01). All women had a reduced number of Tregs compared to men. Treg number was significantly decreased in ESRD patients with HLA antibodies (P < 0.05). Blood transfusion enhanced Treg development in ESRD patients without SLE, unlike the patients with SLE (P < 0.05). ESRD patients with low Treg showed a reduction in TGF-beta 1 and IL-4 and an increase in TNF-alpha and IL-17A levels compared to control groups (P < 0.05-0.0001). However, no change was observed in IL-10 and IFN-gamma levels. Treg frequency was negatively associated with the age of patients (P < 0.01), while this association was not observed in healthy subjects. Based on these findings, it can be observed that reduction in Treg number may contribute to ESRD development in patients with SLE.