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CTLA-4 多态性与异基因造血干细胞移植后的临床结局。

CTLA-4 polymorphism and clinical outcome post allogeneic hematopoietic stem cell transplantation.

机构信息

Bone Marrow Transplantation Laboratory Unit, National Cancer Institute, Cairo University, Cairo, Egypt.

出版信息

Hum Immunol. 2013 Dec;74(12):1643-8. doi: 10.1016/j.humimm.2013.08.002. Epub 2013 Aug 22.

Abstract

CTLA-4 inhibitory molecule plays an important role in regulating T cell activation. It is considered a crucial element in keeping the immune balance and has been implicated in cancer, autoimmunity and transplantation immunology. Inconsistent observations are reported regarding its association with hematopoietic stem cell transplantation (HSCT). Genotyping of CTLA-4 was performed in recipients and their HLA-matched donors for +49A/G and CT60 polymorphisms (80 and 94 pairs, respectively) using PCR-RFLP. No association was encountered between both polymorphisms in patients and donors and acute or chronic graft versus host disease. Significant association was observed between recipient +49A/G G allele and lower disease-free survival and overall survival compared to AA genotype (HR: 2.17, p = 0.03, 95% CI: 1.05-4.48 and HR: 2.54, p = 0.01, 95% CI: 1.16-5.54), respectively. Our results suggest that CTLA-4 genotyping may predict outcome in patients post HSCT. To validate our results, further studies on a larger cohort are needed.

摘要

CTLA-4 抑制分子在调节 T 细胞活化中起着重要作用。它被认为是维持免疫平衡的关键因素,与癌症、自身免疫和移植免疫学有关。关于其与造血干细胞移植 (HSCT) 的关系,报道的观察结果不一致。使用 PCR-RFLP 对受者及其 HLA 匹配供者的 CTLA-4 +49A/G 和 CT60 多态性(分别为 80 对和 94 对)进行基因分型。在患者和供者中,两种多态性均与急性或慢性移植物抗宿主病无关。与 AA 基因型相比,受者 +49A/G G 等位基因与无病生存和总生存的相关性显著降低(HR:2.17,p = 0.03,95%CI:1.05-4.48 和 HR:2.54,p = 0.01,95%CI:1.16-5.54)。我们的结果表明,CTLA-4 基因分型可能预测 HSCT 后患者的预后。为了验证我们的结果,需要对更大的队列进行进一步的研究。

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