Serviço de Hematologia, Hemoterapia e Terapia Celular do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo/Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil.
Regional Blood Center of Ribeirão Preto, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
Transfusion. 2020 Jul;60(7):1573-1578. doi: 10.1111/trf.15832. Epub 2020 May 4.
Red blood cell (RBC) alloimmunization is an important transfusion complication which is prevalent among sickle cell disease (SCD) patients. Autoimmune diseases are a known risk factor for RBC alloimmunization, suggesting that autoimmunity and post-transfusion alloantibody development occur through similar physiopathological pathways. Polymorphisms in the FcγR2B gene have already been associated with several autoimmune disorders and hypothetically could be associated with RBC alloimmunization. Our goal was to evaluate if important polymorphisms of FcγR2B have an impact on the risk of RBC alloimmunization among SCD patients.
This was a case-control study in which alloimmunized and non-alloimmunized SCD patients were compared in terms of the genotype frequency of the FcγR2B polymorphisms -386G/C, -120 T/A, and 695C/T, genotyped through direct Sanger sequencing.
A total of 237 patients met the eligibility criteria, 120 cases (alloimmunized) and 117 controls (non-alloimmunized). RBC alloimmunization was associated with female sex (p < 0.001), lifetime number of RBC units transfused (p = 0.002) and 120 T/A FcγR2B genotype (p = 0.031). The FcγR2B promoter region haplotype 2B.4 (386C120A) was positively associated with RBC alloimunization (p = 0.045). The logistic regression (LR) model identified female sex (OR 10.03, CI 95% 5.16-19.49; p < 0.001) and FcγR2B 2B.4 haplotype (OR 4.55, CI95% 1.1118.65; p = 0.035) as independent predictors of RBC alloimmunization in SCD patients.
SCD patients with the FcγR2B 2B.4 haplotype had over a fourfold higher risk for RBC alloimmunization. This highlights the role played by FcγR2B on RBC alloimmunization and may be helpful in identifying the immune responders.
红细胞（RBC）同种免疫是一种重要的输血并发症，在镰状细胞病（SCD）患者中较为常见。自身免疫性疾病是 RBC 同种免疫的已知危险因素，这表明自身免疫和输血后同种抗体的产生是通过相似的病理生理途径发生的。FcγR2B 基因的多态性已与多种自身免疫性疾病相关，推测其可能与 RBC 同种免疫相关。我们的目标是评估 FcγR2B 的重要多态性是否会影响 SCD 患者 RBC 同种免疫的风险。
这是一项病例对照研究，比较了 RBC 同种免疫和非同种免疫的 SCD 患者在 FcγR2B 多态性-386G/C、-120T/A 和 695C/T 的基因型频率方面的差异，这些多态性通过直接 Sanger 测序进行基因分型。
共有 237 名患者符合入选标准，其中 120 例为病例（同种免疫），117 例为对照（非同种免疫）。RBC 同种免疫与女性性别（p<0.001）、终生输血量（p=0.002）和 FcγR2B 120T/A 基因型（p=0.031）相关。FcγR2B 启动子区域 2B.4 单倍型（386C120A）与 RBC 同种免疫呈正相关（p=0.045）。逻辑回归（LR）模型确定女性性别（OR 10.03，95%CI 5.16-19.49；p<0.001）和 FcγR2B 2B.4 单倍型（OR 4.55，95%CI1.1118.65；p=0.035）是 SCD 患者 RBC 同种免疫的独立预测因子。
携带 FcγR2B 2B.4 单倍型的 SCD 患者发生 RBC 同种免疫的风险增加了四倍以上。这突出了 FcγR2B 在 RBC 同种免疫中的作用，可能有助于识别免疫反应者。
