Document Type : Original Article

Authors

1 Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

2 Center Hospitalier Universitaire (CHU), Nimes, France

3 Chronic kidney disease research center, Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 Chronic Kidney Disease Research Center, Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

5 Nephrology Research Center, Center of Excellence in Nephrology, Tehran University of Medical Sciences, Tehran, Iran

6 Department of Immunology, Tehran University of Medical Sciences, Tehran, Iran

7 Immunology Research Center, Immunology and Infectious Disease Institute, Iran University of Medical Sciences, Tehran, Iran

8 Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Background: Impaired renal function is considered as a significant risk factor for cardiovascular events in chronic kidney disease patients. Several immunosuppressive drugs are used in these patients, which necessitates to minimize the drug-related side effects by employing alternative strategies.
Objective: This study aimed to evaluate prospectively the influence of low dose ATG induction therapy with two different protocols (Sirolimus versus Mycophenolate mofetil) on the expression of functional markers (LAG-3, CD39, and intracellular CTLA-4) on conventional Tregs in renal recipients.
Methods: Thirty-eight renal transplant recipients were enrolled in this study. The patients were randomly assigned into two groups, including TMP: Tacrolimus (Tac), Mycophenolate mofetil (MMF), and Prednisolone (n=23); and TSP: Tac, Sirolimus (SRL), and Prednisolone (n=15). The frequency of LAG-3, CD39, and intracellular CTLA-4 on circulating Tregs was analyzed by flow cytometry before and after transplantation.
Results: Analysis of the flow cytometry data showed that the frequency of CD4+CD25+FOXP3+ Tregs increased 4 months post-transplantation compared to pre-transplantation in both groups, although this increase was only significant in TMP group. In TMP treated patients, the frequency of LAG-3+ Tregs and CD39+ Tregs increased, whereas the frequency of intracellular CTLA-4+ Tregs decreased 4 months post-transplantation. In TSP group, while the frequency of CD39+ Tregs increased, the frequency of CTLA-4+ Tregs decreased in post-transplantation compared to pre-transplantation.
Conclusions: it seems that both treatment regimen protocols with a low dose ATG induction therapy may be clinically applicable in kidney transplant recipients.

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