Role of circulating CD4+CD25+FOXP-3+T-regulatory cells and FOXP-3 rs3761548 gene polymorphism in acute liver allograft rejection

Ghoneim, Enas M.; Ghonaim, Mabrouk M.; Makled, Amal F.; Altabbakh, Mohamed A.; Helwa, Mohamed; Salem, Radwa H.; Awad, Samah M.

doi:10.21608/ejmm.2020.250255

Role of circulating CD4+CD25+FOXP-3+T-regulatory cells and FOXP-3 rs3761548 gene polymorphism in acute liver allograft rejection

Document Type : New and original researches in the field of Microbiology.

Authors

¹ Department of Clinical Microbiology and Immunology, National Liver Institute, Menoufia University, Egypt

² Department of Medical Microbiology and Immunology, Faculty of Medicine, Menoufia University, Egypt

³ Department of Hepatology, National Liver Institute, Menoufia University, Egypt

⁴ Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Egypt

10.21608/ejmm.2020.250255

Abstract

Background: FOXP3 gene, is a major regulator of T-regulatory (Treg) cells that have a critical role in immune responses to alloantigens and acute cellular rejection (ACR) after liver transplantation (LT). Objectives: To investigate the role of FOXP-3 rs3761548 gene polymorphism on ACR after LT and to determine the relation between the circulating CD4+CD25+FOXP-3+Treg cells, and infection on the severity of ACR. Methodology: Blood samples were obtained from 60 allograft liver recipients and 20 healthy volunteers. FOXP-3 (rs3761548) polymorphism was studied using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Flowcytometry was used to enumerate circulating CD4+CD25+FOXP-3+Treg cells in peripheral blood of liver transplant recipients. Results: Bacterial and candida infections were more significantly detected in liver transplant recipients with ACR. A significant predominance of the AA genotype and the A allele of FOXP3 gene (rs3761548) was found in liver transplant recipients with compared to those without ACR. Highly significant reduction in percentage and count of CD4+and Treg cells were demonstrated in the liver transplant recipients with ACR. A significant negative correlation was detected between degree of ACR and percentage and count of Treg cells. Conclusion: Genetic polymorphism of FOXP-3 (rs3761548) and decreased percentage and count of Treg cells were associated with ACR. Carriers of the AA genotype and the A allele were more liable to severe degree of ACR after LT.

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