Discrimination of primary and chronic cytomegalovirus infection based on humoral immune profiles in pregnancy.

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Andrew P Hederman, Christopher Al Remmel, Shilpee Sharma, Harini Natarajan, Joshua A Weiner, Daniel Wrapp, Catherine Donner, Marie-Luce Delforge, Piera d'Angelo, Milena Furione, Chiara Fornara, Jason S McLellan, Daniele Lilleri, Arnaud Marchant, Margaret E Ackerman
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引用次数: 0

Abstract

BACKGROUNDMost humans have been infected with cytomegalovirus (CMV) by midlife without clinical signs of disease. However, in settings in which the immune system is undeveloped or compromised, the virus is not adequately controlled and consequently presents a major infectious cause of both congenital disease during pregnancy as well as opportunistic infection in children and adults. With clear evidence that risk to the fetus varies with gestational age at the time of primary maternal infection, further research on humoral responses to primary CMV infection during pregnancy is needed.METHODSHere, systems serology tools were applied to characterize antibody responses to CMV infection in pregnant and nonpregnant women experiencing either primary or chronic infection.RESULTSWhereas strikingly different antibody profiles were observed depending on infection status, limited differences were associated with pregnancy status. Beyond known differences in IgM responses used clinically for identification of primary infection, distinctions observed in IgA and FcγR-binding antibodies and among antigen specificities accurately predicted infection status. Machine learning was used to define the transition from primary to chronic states and predict time since infection with high accuracy. Humoral responses diverged over time in an antigen-specific manner, with IgG3 responses toward tegument decreasing over time as typical of viral infections, while those directed to pentamer and glycoprotein B were lower during acute and greatest during chronic infection.CONCLUSIONIn sum, this work provides insights into the antibody response associated with CMV infection status in the context of pregnancy, revealing aspects of humoral immunity that have the potential to improve CMV diagnostics.FUNDINGCYMAF consortium and NIH NIAID.

根据妊娠期体液免疫图谱区分原发性和慢性巨细胞病毒感染。
背景:大多数人在四十岁之前就已经感染了巨细胞病毒(CMV)。虽然大多数巨细胞病毒感染都能被免疫系统很好地控制,但先天性感染可导致严重的健康影响,甚至导致胎儿和新生儿死亡。大多数人在中年时已经感染了巨细胞病毒(CMV),但没有临床症状。然而,在免疫系统不发达或受损的情况下,病毒得不到充分控制,因此成为孕期先天性疾病以及儿童和成人机会性感染的主要传染病因。有明确证据表明,母体慢性感染对胎儿的风险较低,且与母体原发感染时的胎龄有关,因此需要进一步研究妊娠期原发 CMV 感染的体液免疫反应。方法:本文应用系统血清学工具描述了原发或慢性感染的孕妇和非孕妇对 CMV 感染的抗体反应:结果:根据感染状态观察到了明显不同的抗体特征,而与怀孕状态相关的差异则较为有限。除了临床上用于识别原发性感染的 IgM 反应的已知差异外,在横断面队列中观察到的 IgA 和 FcγR 结合抗体反应以及病毒抗原特异性之间的差异也能准确预测感染状态。利用机器学习技术,纵向样本也被用来定义 CMV 感染从原发状态向慢性状态过渡的免疫时钟,并准确预测原发感染后的时间。随着时间的推移,体液反应以抗原特异性的方式出现分化,IgG3对皮损的反应随着时间的推移而降低,这是病毒感染的典型特征,而针对五聚体和糖蛋白B的反应在急性感染期间较低,在慢性感染期间最高:总之,这项研究为了解妊娠期CMV感染状态相关的抗体反应提供了新的视角,揭示了体液免疫的各个方面,有可能改善CMV的诊断,并为减少CMV母婴传播的干预措施的临床试验提供支持:试验注册:不适用CYMAF联盟和美国国立卫生研究院。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Clinical Investigation
Journal of Clinical Investigation 医学-医学:研究与实验
CiteScore
24.50
自引率
1.30%
发文量
1034
审稿时长
2 months
期刊介绍: The Journal of Clinical Investigation, established in 1924 by the ASCI, is a prestigious publication that focuses on breakthroughs in basic and clinical biomedical science, with the goal of advancing the field of medicine. With an impressive Impact Factor of 15.9 in 2022, it is recognized as one of the leading journals in the "Medicine, Research & Experimental" category of the Web of Science. The journal attracts a diverse readership from various medical disciplines and sectors. It publishes a wide range of research articles encompassing all biomedical specialties, including Autoimmunity, Gastroenterology, Immunology, Metabolism, Nephrology, Neuroscience, Oncology, Pulmonology, Vascular Biology, and many others. The Editorial Board consists of esteemed academic editors who possess extensive expertise in their respective fields. They are actively involved in research, ensuring the journal's high standards of publication and scientific rigor.
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