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巨细胞病毒(CMV)基因型与异基因造血干细胞移植。

Cytomegalovirus (CMV) genotype in allogeneic hematopoietic stem cell transplantation.

机构信息

Department of Clinical Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.

出版信息

BMC Infect Dis. 2013 Jul 10;13:310. doi: 10.1186/1471-2334-13-310.

Abstract

BACKGROUND

Based on sequence variation in the UL55 gene that encodes glycoprotein B (gB), human cytomegalovirus (CMV) can be classified into four gB genotypes. Previous studies have suggested an association between CMV gB genotype and clinical outcome in patients who underwent an allogeneic hematopoietic stem cell transplant (HSCT). The goals of this study were identify patients with active infection caused by CMV in recipients of HSCT; determine the prevalence of CMV genotypes in the study group; correlate genotype with CMV disease, acute GVHD and overall survival.

METHODS

The diagnosis of active CMV infection after allogeneic HSCT was detected by antigenemia (AGM) and/or nested-PCR (N-PCR). Positive samples from patients with active CMV infection were submitted to genotyping using N-PCR to amplify a region of UL55, followed by restriction analysis based on HinfI and RsaI digestion. Real-time PCR (qPCR) was used to determine the viral load during active CMV infection and antiviral treatment.

RESULTS

Sixty-three allogeneic HSCT recipients were prospectively evaluated; 49/63 (78%) patients were infected with CMV genotypes - gB1 19/49 (39%), gB2 17/49 (35%), gB3 3/49 (6%), gB4 7/49 (14%) - and 3 (6%) had mixed CMV genotypes (gB1 + gB3, gB1 + gB4 and gB2 + gB4). Characterized by gastrointestinal disease, CMV disease occurred in 3/49 (6.1%) patients, who had CMV gB3 genotype. These gB3 genotype patients presented an increasing AGM number, mean 125 (± 250) (P = 0.70), and qPCR copies/ml, mean 37938 (SD ± 50542) (P = 0.03), during antiviral treatment, when compared with other CMV genotypes. According to CMV genotypes, stratified overall survival was 55% for gB1, 43% for gB2; 0% for gB3 and 57% for gB4 (P = 0.03).

CONCLUSIONS

One of the restrictions of the presented study was the low number of CMV gB sub-cohorts). However, we demonstrated that the frequency of active CMV infection in this HSCT population was high, and the most prevalent genotype in these patients with active CMV infection was gB1 and gB2 genotype (74%). In Brazil, HSCT recipients seem to carry mainly gB1 and gB2 CMV genotype.

摘要

背景

根据编码糖蛋白 B (gB) 的 UL55 基因的序列变异,人巨细胞病毒 (CMV) 可分为 4 种 gB 基因型。先前的研究表明,CMV gB 基因型与接受异基因造血干细胞移植 (HSCT) 的患者的临床结局有关。本研究的目的是确定 HSCT 受者中由 CMV 引起的活动性感染患者;确定研究组中 CMV 基因型的流行率;将基因型与 CMV 疾病、急性移植物抗宿主病和总生存率相关联。

方法

通过抗原血症 (AGM) 和/或巢式 PCR (N-PCR) 检测异基因 HSCT 后 CMV 活动性感染的诊断。对患有活动性 CMV 感染的患者的阳性样本进行 N-PCR 扩增 UL55 区,然后进行基于 HinfI 和 RsaI 消化的限制性分析。实时 PCR (qPCR) 用于检测活动性 CMV 感染和抗病毒治疗期间的病毒载量。

结果

对 63 例异基因 HSCT 受者进行前瞻性评估;49/63 (78%) 患者感染了 CMV 基因型 - gB1 19/49 (39%)、gB2 17/49 (35%)、gB3 3/49 (6%)、gB4 7/49 (14%) - 3 (6%) 具有混合 CMV 基因型(gB1 + gB3、gB1 + gB4 和 gB2 + gB4)。以胃肠道疾病为特征的 CMV 疾病发生在 3/49 (6.1%) 患者中,这些患者为 CMV gB3 基因型。这些 gB3 基因型患者在抗病毒治疗期间的 AGM 数量(平均值 125(±250))和 qPCR 拷贝/ml(平均值 37938(SD ±50542))均呈增加趋势,与其他 CMV 基因型相比,差异均有统计学意义(P=0.70)。根据 CMV 基因型分层的总生存率为 gB1 为 55%,gB2 为 43%;gB3 为 0%,gB4 为 57%(P=0.03)。

结论

本研究的局限性之一是 CMV gB 亚群的数量较少。然而,我们证明了该 HSCT 人群中 CMV 活动性感染的频率很高,并且在这些患有活动性 CMV 感染的患者中最常见的基因型是 gB1 和 gB2 基因型(74%)。在巴西,HSCT 受者似乎主要携带 gB1 和 gB2 CMV 基因型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4cb/3727998/6a13cb087898/1471-2334-13-310-1.jpg

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