Oliveira V B, Dezan M R, Gomes F C A, Menosi Gualandro S F, Krieger J E, Pereira A C, Marsiglia J D, Levi J E, Rocha V, Mendrone-Junior A, Sabino E C, Dinardo C L
Fundação Pró-Sangue Hemocentro de São Paulo, São Paulo, São Paulo, Brazil.
Discipline of Hematology, University of São Paulo School of Medicine, São Paulo, São Paulo, Brazil.
Int J Immunogenet. 2017 Oct;44(5):219-224. doi: 10.1111/iji.12334. Epub 2017 Aug 17.
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.
细胞毒性T淋巴细胞相关抗原4（CTLA-4）分子表达于T淋巴细胞膜上，对抗原呈递过程产生负向影响。由于基因多态性导致的CTLA-4表达降低与自身免疫性疾病风险增加相关，其病理生理学与输血后红细胞（RBC）同种免疫相似。我们的目标是评估影响蛋白质表达的CTLA-4基因多态性是否与RBC同种免疫相关。这是一项病例对照研究，纳入了134例镰状细胞病（SCD）患者和253例非SCD患者。所有患者均对CTLA-4基因的49A/G和-318C/T多态性进行基因分型。无论临床混杂因素如何，-318C/T的基因型频率在同种免疫和未同种免疫的SCD患者之间存在显著差异（p = 0.016）。携带-318T等位基因杂合子的SCD患者出现同种抗体的风险更高（OR：5.4，CI：1.15 - 25.6）。总之，CTLA-4基因的-318C/T多态性与SCD患者的RBC同种免疫相关。这突出了CTLA-4在输血后同种抗体产生中所起的作用。
