Analysis of CTLA-4 -318C/T Polymorphism in Thalassemia Patients Transfused at the Casablanca Children's Hospital (Morocco)

Abstract

Red blood cells (RBC) alloimmunization is a delayed adverse transfusion reaction in thalassemia patients. The mechanisms behind the inhibition or tolerance of red blood cells are still poorly understood. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) molecule is expressed on Treg -lymphocyte membrane and is an inhibitory molecule which plays the mediator role of peripheral tolerance and maintains tolerance to self-antigens. Recent studies have reported that defect in the CTLA-4 gene expression could affect its function and be involved in the development of various pathologies as autoimmune diseases and the outcome after Allogenic hematopoietic stem cell transplantation; indeed, the objective of our study is the search for the association of the CTLA-4 polymorphism with the susceptibility to red blood cells alloimmunizations. In this study we looked for the polymorphism of the CTLA-4 gene at the -318 C/T position in 35 β-thalassemic patients (15alloimmunized and 20 non alloimunized) followed at the children's hospital in Casablanca, and 20 healthy controls, by PCR-RFLP and Sanger sequencing. In our cohort, none of the group cases revealed the mutation carried out by PCR RFLP. Indeed, this result was confirmed by Sanger sequencing. This study does not find an association of -318C/T SNPs in CTLA-4 gene and RBC alloimmunization among our cohort. Following these preliminary results, an investigation of the other exons of the CTLA-4 gene on a large cohort is necessary to complete this study.