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手术肠标本中巨细胞病毒感染在坏死性小肠结肠炎和自发性肠穿孔婴儿中的高发生率:一项回顾性观察研究。

High prevalence of cytomegalovirus infection in surgical intestinal specimens from infants with necrotizing enterocolitis and spontaneous intestinal perforation: A retrospective observational study.

机构信息

Department of Medicine, Exp Cardiovascular Research Unit and Department of Neurology, Center for Molecular Medicine, Solna, Karolinska Institute, Stockholm, Sweden.

Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

出版信息

J Clin Virol. 2017 Aug;93:57-64. doi: 10.1016/j.jcv.2017.05.022. Epub 2017 Jun 3.

Abstract

BACKGROUND

Necrotizing enterocolitis (NEC) is a severe, often fatal gastrointestinal emergency that predominantly affects preterm infants, and there is evidence that neonatal cytomegalovirus (CMV) infection may in some cases contribute to its pathogenesis.

OBJECTIVES

This study aimed to evaluate the prevalence of CMV in infants with NEC.

STUDY DESIGN

Seventy intestinal specimens from 61 infants with NEC, spontaneous intestinal perforation (SIP), or related surgical complications were collected at Karolinska University Hospital and Uppsala University Hospital, Sweden. Ten specimens from autopsied infants without bowel disease served as controls. Samples were analyzed for CMV immediate-early antigen (IEA), CMV late antigen (LA), 5-lipoxigenase (5LO) and CMV-DNA by immunohistochemistry (IHC) and in situ hybridization (ISH), respectively. In 10 index samples, CMV DNA was analyzed with Taqman PCR after laser capture microdissection (LCM) of cells positive for CMV IEA by IHC.

RESULTS

CMV IEA was detected by IHC in 57 (81%) and CMV LA in 45 (64%) of 70 intestinal specimens from index cases; 2 (20%) of 10 control specimens were positive for both antigens. 5LO was detected in intestinal tissue section obtained from all examined index and controls. CMV DNA was detected in 4 of 10 samples (40%) after LCM. By ISH, all 13 IHC-IEA-positive samples were positive for CMV DNA; however, 3 of 5 IHC-IEA-negative samples (60%) were also positive.

CONCLUSIONS

CMV-specific antigens and CMV DNA were highly prevalent in intestinal specimens from infants with NEC, SIP, and related surgical complications. Our findings provide further evidence that neonatal CMV infection contributes to the pathogenesis of these diseases and may affect patient outcome.

摘要

背景

坏死性小肠结肠炎(NEC)是一种严重的、常致命的胃肠道急症,主要影响早产儿,有证据表明,新生儿巨细胞病毒(CMV)感染在某些情况下可能有助于其发病机制。

目的

本研究旨在评估 NEC 患儿中 CMV 的流行情况。

研究设计

在瑞典卡罗林斯卡大学医院和乌普萨拉大学医院收集了 61 例 NEC、自发性肠穿孔(SIP)或相关手术并发症婴儿的 70 个肠标本,10 个无肠道疾病的尸检婴儿标本作为对照。分别采用免疫组化(IHC)和原位杂交(ISH)法分析标本中的 CMV 早期抗原(IEA)、CMV 晚期抗原(LA)、5-脂氧合酶(5LO)和 CMV-DNA。在 10 个指数样本中,通过激光捕获微切割(LCM)后,用 Taqman PCR 分析 CMV IEA 阳性细胞的 CMV DNA。

结果

IHC 检测到 70 个指数样本中 57 个(81%)和 45 个(64%)的 CMV IEA,10 个对照样本中 2 个(20%)均为阳性。所有检测的指数和对照组织切片中均检测到 5LO。经 LCM 后,10 个样本中的 4 个(40%)检测到 CMV DNA。ISH 检测结果显示,13 个 IHC-IEA 阳性样本均为 CMV DNA 阳性,而 5 个 IHC-IEA 阴性样本中 3 个(60%)也为阳性。

结论

NEC、SIP 和相关手术并发症婴儿的肠道标本中 CMV 特异性抗原和 CMV DNA 高度流行。我们的研究结果进一步表明,新生儿 CMV 感染有助于这些疾病的发病机制,并可能影响患者的预后。

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