Shiraz Transplant Research Center, Namazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
Mol Biol Rep. 2013 Oct;40(10):5833-42. doi: 10.1007/s11033-013-2689-x. Epub 2013 Sep 22.
Determinative associations may exist between costimulatory molecule gene polymorphisms with a variety of post hematopoietic stem cell transplantation (HSCT) viral related clinical outcomes especially acute graft versus host disease (aGVHD). Therefore in this study the associations between costimulatory molecule gene polymorphisms including: cytotoxic T-lymphocyte antigen-4 (CTLA4), programmed cell death-1 (PD-1), inducible T cell costimulator (ICOS), and cluster differentiation 28 (CD28) with active cytomegalovirus (CMV) infection were evaluated in HSCT patients. The 72 allogeneic HSCT patients with and without aGVHD were enrolled in this cross sectional study between years: 2004-2011. The single nucleotide polymorphisms in loci of the costimulatory molecules including: CTLA4 gene (-318 C/T, 1722 T/C, 1661 A/G, +49 A/G), PD-1 gene (PD-1.3 A/G, PD-1.9 C/T), ICOS gene (1720 C/T), and CD28 gene (+17 C/T) were analyzed in studied HSCT patients by PCR-RFLP methods. The active CMV infection was evaluated in fresh EDTA-treated blood samples of each allogeneic HSCT patients by CMV antigenemia kit according to manufacturer's instruction. Active CMV infection was found in 11 of 72 (15.27 %) of allogeneic HSCT patients. The T allele and TT genotype of the CD28 +17 C/T were significantly higher frequency in active CMV infected allogeneic HSCT patients experienced aGVHD. The G allele and GG genotype of the CTLA4 -1661 A/G were significantly higher frequent in active CMV infected allogeneic HSCT patients experienced low grade of aGVHD. Finally, finding of significant associations between CD28 +17 C/T and CTLA4 -1661 A/G genotypes with CMV active infection in allogeneic HSCT patients experienced aGVHD emphasize on the importance of the genetic pattern of costimulatory genes in outcomes of active CMV infection in HSCT patients needs completed studies.
在造血干细胞移植（HSCT）后多种与病毒相关的临床结果，尤其是急性移植物抗宿主病（aGVHD）中，共刺激分子基因多态性可能存在决定性关联。因此，在这项研究中，评估了共刺激分子基因多态性与 HSCT 患者活动性巨细胞病毒（CMV）感染之间的关联，这些基因包括细胞毒性 T 淋巴细胞抗原 4（CTLA4）、程序性细胞死亡 1（PD-1）、诱导性 T 细胞共刺激分子（ICOS）和分化簇 28（CD28）。这项病例对照研究纳入了 2004 年至 2011 年间的 72 例异基因 HSCT 患者，包括有和无 aGVHD 的患者。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法分析了研究 HSCT 患者共刺激分子基因座中的单核苷酸多态性，包括 CTLA4 基因（-318 C/T、1722 T/C、1661 A/G、+49 A/G）、PD-1 基因（PD-1.3 A/G、PD-1.9 C/T）、ICOS 基因（1720 C/T）和 CD28 基因（+17 C/T）。根据制造商的说明，通过 CMV 抗原血症试剂盒评估新鲜 EDTA 处理的每份异基因 HSCT 患者的血液样本中的活动性 CMV 感染。在 72 例异基因 HSCT 患者中，有 11 例（15.27%）发现活动性 CMV 感染。在发生 aGVHD 的异基因 HSCT 患者中，CD28+17 C/T 的 T 等位基因和 TT 基因型的频率显著更高。在发生低级别 aGVHD 的异基因 HSCT 患者中，CTLA4-1661 A/G 的 G 等位基因和 GG 基因型的频率显著更高。最后，在发生 aGVHD 的异基因 HSCT 患者中，CD28+17 C/T 和 CTLA4-1661 A/G 基因型与 CMV 活动性感染之间存在显著关联，这强调了共刺激基因遗传模式在 HSCT 患者 CMV 活动性感染结果中的重要性，需要进一步研究。
