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根据供体和受者 CCR5、MCP-1、IL-10 和 TLR9 基因中的单核苷酸多态性,评估异基因造血干细胞移植患者中活性巨细胞病毒感染的发生率和动态变化。

Incidence and dynamics of active cytomegalovirus infection in allogeneic stem cell transplant patients according to single nucleotide polymorphisms in donor and recipient CCR5, MCP-1, IL-10, and TLR9 genes.

机构信息

Microbiology Service, Hospital Clínico Universitario, Fundación INCLIVA, Valencia, Spain.

出版信息

J Med Virol. 2015 Feb;87(2):248-55. doi: 10.1002/jmv.24050. Epub 2014 Aug 17.

Abstract

Single nucleotide polymorphisms (SNPs) in genes involved in the activation or regulation of innate and adaptive immune responses may modulate the susceptibility to and the natural history of certain chronic viral infections. The current study aimed to investigate whether donor and recipient SNPs in the chemokine receptor 5 (rs1800023), monocyte chemoattractant protein 1 (rs13900), interleukin-10 (rs1878672), and Toll-like receptor 9 (rs352140) genes would exert any influence on the rate of incidence and features of CMV DNAemia in the allogeneic stem cell transplantation setting. This was a retrospective observational multicenter study. The cohort consisted of 102 non-consecutive allogeneic stem cell transplant recipients. SNP genotyping was performed by allele-specific real-time PCR. CMV surveillance was performed by the pp65 antigenemia assay/and or by real-time PCR. Seventy-three patients developed CMV DNAemia within the first 100 days after transplantation (71.5%). Neither donor nor recipient SNPs were associated significantly with the rate of incidence of active CMV infection, nor with the need for pre-emptive antiviral therapy. Both the duration of CMV DNAemia and the plasma CMV DNA peak load during episodes were significantly higher in patients harboring the donor (but not the recipient) chemokine receptor 5 A/A genotype, than in their A/G and G/G counterparts (P = 0.022 and P = 0.045, respectively). The data reported suggest that SNPs in chemokine receptor 5 may influence the dynamics of CMV infection in the Allo-SCT setting.

摘要

单核苷酸多态性(SNPs)在参与固有和适应性免疫反应的激活或调节的基因中,可能调节某些慢性病毒感染的易感性和自然史。本研究旨在探讨趋化因子受体 5(rs1800023)、单核细胞趋化蛋白 1(rs13900)、白细胞介素-10(rs1878672)和 Toll 样受体 9(rs352140)基因中的供体和受体 SNPs 是否会对同种异体干细胞移植背景下 CMV DNAemia 的发生率和特征产生任何影响。这是一项回顾性观察性多中心研究。该队列包括 102 例非连续异体干细胞移植受者。通过等位基因特异性实时 PCR 进行 SNP 基因分型。通过 pp65 抗原血症测定/和或实时 PCR 进行 CMV 监测。73 例患者在移植后 100 天内发生 CMV DNAemia(71.5%)。供体和受体 SNPs 均与活动性 CMV 感染的发生率或预防性抗病毒治疗的需要无显著相关性。携带供体趋化因子受体 5 A/A 基因型的患者比携带 A/G 和 G/G 基因型的患者的 CMV DNAemia 持续时间和感染期间的血浆 CMV DNA 峰值负荷均显著更高(P=0.022 和 P=0.045)。报告的数据表明,趋化因子受体 5 中的 SNPs 可能影响同种异体干细胞移植背景下 CMV 感染的动力学。

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