‐318C/T polymorphism of the CTLA‐4 gene is an independent risk factor for RBC alloimmunization among sickle cell disease patients |
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| Authors: | V. B. Oliveira M. R. Dezan F. C. A. Gomes S. F. Menosi Gualandro J. E. Krieger A. C. Pereira J. D. Marsiglia J. E. Levi V. Rocha A. Mendrone‐Junior E. C. Sabino C. L. Dinardo |
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| Affiliation: | 1. Funda??o Pró‐Sangue Hemocentro de S?o Paulo, S?o Paulo, S?o Paulo, Brazil;2. Discipline of Hematology, University of S?o Paulo School of Medicine, S?o Paulo, S?o Paulo, Brazil;3. Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of S?o Paulo School of Medicine, S?o Paulo, S?o Paulo, Brazil;4. Institute of Tropical Medicine, University of S?o Paulo, S?o Paulo, S?o Paulo, Brazil |
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| Abstract: | Cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4) molecule is expressed on T‐lymphocyte membrane and negatively influences the antigen‐presenting process. Reduced expression of CTLA‐4 due to gene polymorphisms is associated with increased risk of autoimmune disorders, whose physiopathology is similar to that of post‐transfusion red blood cell (RBC) alloimmunization. Our goal was to evaluate if polymorphisms of CTLA‐4 gene that affect protein expression are associated with RBC alloimmunization. This was a case–control study in which 134 sickle cell disease (SCD) patients and 253 non‐SCD patients were included. All patients were genotyped for the polymorphisms 49A/G and ‐318C/T of CTLA‐4 gene. The genotype frequency of ‐318C/T differed significantly between alloimmunized and nonalloimmunized SCD patients, irrespective of clinical confounders (p = .016). SCD patients heterozygous for ‐318T allele presented higher risk of alloantibody development (OR: 5.4, CI: 1.15–25.6). In conclusion, the polymorphism ‐318C/T of CTLA‐4 gene is associated with RBC alloimmunization among SCD patients. This highlights the role played by CTLA‐4 on post‐transfusion alloantibody development. |
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| Keywords: | alloimmunization CTLA‐4 polymorphism sickle cell |
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