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.
Highlights
The transfusion therapy remains the conventional and essential treatment for thalassemia patients to this day [1], [2]
It is confronted to Red blood cells (RBC) alloimmunizations challenge by erythrocyte phenotypic missmatched between donors and recipients [3]-[6] leading to delayed transfusion hemolysis and difficulties to finding compatible units leading to a transfusion deadlock [7]
The alloimmunization can affect the outcomes after allogeneic hematopoietic stem cell transplants (HSCT) and increase the transplant rejection risk [8]
Summary
The transfusion therapy remains the conventional and essential treatment for thalassemia patients to this day [1], [2]. The identification of regulatory T lymphocytes (Tregs) among the CD4 + CD25 + T cell subset as a key regulators of peripheral tolerance in mice as well as in humans has ushered in an exciting era in prevention and treatment of autoimmune diseases and for the improvement of organ transplantation [11]. Their potential to induce transfusion tolerance remains to be explored
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