新生儿 T 细胞免疫应答与先天性巨细胞病毒感染的长期后果（CYTRIC 研究）。

T-Cell Immune Responses in Newborns and Long-Term Sequelae in Congenital Cytomegalovirus Infection (CYTRIC Study).

机构信息

Centro de Salud Ciudad Jardín, Pediatric Department, Alicante, Spain.

Instituto de Investigación Hospital 12 de Octubre (Imas12), Fundación Biomédica del Hospital Universitario 12 de Octubre (FBHU12O), Madrid, Spain.

出版信息

J Pediatr. 2024 Sep;272:114084. doi: 10.1016/j.jpeds.2024.114084. Epub 2024 May 4.

DOI:10.1016/j.jpeds.2024.114084

PMID:38705230

Abstract

OBJECTIVE

The objective of this study was to assess the role of T-lymphocyte immune responses in newborns with congenital cytomegalovirus (CMV) infection (cCMV) and their potential association with the development of long-term sequelae.

STUDY DESIGN

A multicenter, prospective study from 2017 to 2022 was conducted across 8 hospitals in Spain. Blood samples were collected within the first month of life from neonates diagnosed with cCMV. Intracellular cytokine staining was employed to evaluate the presence of CMV-specific interferon-gamma (IFN-γ)-producing CD8 and CD4 T lymphocytes (CMV-IFN-γ-CD8/CD4) using flow cytometry. The development of sequelae, including hearing loss and neurologic impairment, was assessed during follow-up.

RESULTS

In total, 64 newborns were included; 42 infants (65.6%) had symptomatic cCMV. The median age at the last follow-up visit was 25.3 months (IQR 20.1-34.4). Eighteen infants had long-term sequelae (28.1%), predominantly hearing loss (20.3%) and neurologic disorders (15.6%). No relationship was observed between total count or percentage of CMV-specific IFN-γ-CD8 or CD4 lymphocytes and long-term sequelae. Multivariable analysis demonstrated an association between lower total lymphocyte count and long-term sequelae (aOR 0.549, 95% CI: 0.323-0.833), which requires further study.

CONCLUSIONS

CMV-specific IFN-γ-CD4 and CD8 T-lymphocyte responses in neonates with cCMV were not predictive of long-term sequelae.

摘要

目的

本研究旨在评估先天性巨细胞病毒（cCMV）感染新生儿 T 淋巴细胞免疫应答的作用及其与长期后遗症发展的潜在关联。

研究设计

这是一项 2017 年至 2022 年在西班牙 8 家医院进行的多中心前瞻性研究。从诊断为 cCMV 的新生儿中采集出生后第一个月内的血样。采用细胞内细胞因子染色，通过流式细胞术评估 CMV 特异性干扰素-γ（IFN-γ）产生的 CD8 和 CD4 T 淋巴细胞（CMV-IFN-γ-CD8/CD4）的存在。在随访期间评估后遗症的发展，包括听力损失和神经功能障碍。

结果

共纳入 64 名新生儿；42 名婴儿（65.6%）患有有症状的 cCMV。最后一次随访时的中位年龄为 25.3 个月（IQR 20.1-34.4）。18 名婴儿有长期后遗症（28.1%），主要为听力损失（20.3%）和神经障碍（15.6%）。CMV 特异性 IFN-γ-CD8 或 CD4 淋巴细胞的总数或百分比与长期后遗症之间未见相关性。多变量分析表明，总淋巴细胞计数较低与长期后遗症有关（aOR 0.549，95%CI：0.323-0.833），这需要进一步研究。