Tatari-Calderone Zohreh, Tamouza Ryad, Le Bouder Gama P, Dewan Ramita, Luban Naomi L C, Lasserre Jacqueline, Maury Jacqueline, Lionnet François, Krishnamoorthy Rajagopal, Girot Robert, Vukmanovic Stanislav
Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010-2970, USA.
Clin Dev Immunol. 2013;2013:937846. doi: 10.1155/2013/937846. Epub 2013 May 22.
The goal of the present work was to identify the candidate genetic markers predictive of alloimmunization in sickle cell disease (SCD). Red blood cell (RBC) transfusion is indicated for acute treatment, prevention, and abrogation of some complications of SCD. A well-known consequence of multiple RBC transfusions is alloimmunization. Given that a subset of SCD patients develop multiple RBC allo-/autoantibodies, while others do not in a similar multiple transfusional setting, we investigated a possible genetic basis for alloimmunization. Biomarker(s) which predicts (predict) susceptibility to alloimmunization could identify patients at risk before the onset of a transfusion program and thus may have important implications for clinical management. In addition, such markers could shed light on the mechanism(s) underlying alloimmunization. We genotyped 27 single nucleotide polymorphisms (SNPs) in the CD81, CHRNA10, and ARHG genes in two groups of SCD patients. One group (35) of patients developed alloantibodies, and another (40) had no alloantibodies despite having received multiple transfusions. Two SNPs in the CD81 gene, that encodes molecule involved in the signal modulation of B lymphocytes, show a strong association with alloimmunization. If confirmed in prospective studies with larger cohorts, the two SNPs identified in this retrospective study could serve as predictive biomarkers for alloimmunization.
本研究的目的是确定镰状细胞病（SCD）中预测同种免疫的候选基因标记物。红细胞（RBC）输血适用于SCD某些并发症的急性治疗、预防和消除。多次红细胞输血的一个众所周知的后果是同种免疫。鉴于一部分SCD患者会产生多种红细胞同种/自身抗体，而其他患者在类似的多次输血情况下则不会，我们研究了同种免疫可能的遗传基础。预测同种免疫易感性的生物标志物可以在输血计划开始前识别出有风险的患者，因此可能对临床管理具有重要意义。此外，这些标记物可以揭示同种免疫的潜在机制。我们对两组SCD患者的CD81、CHRNA10和ARHG基因中的27个单核苷酸多态性（SNP）进行了基因分型。一组（35名）患者产生了同种抗体，另一组（40名）尽管接受了多次输血但没有产生同种抗体。编码参与B淋巴细胞信号调节分子的CD81基因中的两个SNP与同种免疫密切相关。如果在更大队列的前瞻性研究中得到证实，本回顾性研究中确定的两个SNP可作为同种免疫的预测生物标志物。
