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巴西寨卡病毒感染患者中与神经并发症及先天性中枢神经系统异常相关的特定生物标志物

Specific Biomarkers Associated With Neurological Complications and Congenital Central Nervous System Abnormalities From Zika Virus-Infected Patients in Brazil.

作者信息

Kam Yiu-Wing, Leite Juliana Almeida, Lum Fok-Moon, Tan Jeslin J L, Lee Bernett, Judice Carla C, Teixeira Daniel Augusto de Toledo, Andreata-Santos Robert, Vinolo Marco A, Angerami Rodrigo, Resende Mariangela Ribeiro, Freitas Andre Ricardo Ribas, Amaral Eliana, Junior Renato Passini, Costa Maria Laura, Guida José Paulo, Arns Clarice Weis, Ferreira Luis Carlos S, Rénia Laurent, Proença-Modena Jose Luiz, Ng Lisa F P, Costa Fabio T M

机构信息

Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR).

Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas (Unicamp), São Paulo.

出版信息

J Infect Dis. 2017 Jul 15;216(2):172-181. doi: 10.1093/infdis/jix261.

Abstract

BACKGROUND

Zika virus (ZIKV) infections have been linked to different levels of clinical outcomes, ranging from mild rash and fever to severe neurological complications and congenital malformations.

METHODS

We investigated the clinical and immunological response, focusing on the immune mediators profile in 95 acute ZIKV-infected adult patients from Campinas, Brazil. These patients included 6 pregnant women who later delivered during the course of this study. Clinical observations were recorded during hospitalization. Levels of 45 immune mediators were quantified using multiplex microbead-based immunoassays.

RESULTS

Whereas 11.6% of patients had neurological complications, 88.4% displayed mild disease of rash and fever. Several immune mediators were specifically higher in ZIKV-infected patients, and levels of interleukin 10, interferon gamma-induced protein 10 (IP-10), and hepatocyte growth factor differentiated between patients with or without neurological complications. Interestingly, higher levels of interleukin 22, monocyte chemoattractant protein 1, TNF-α, and IP-10 were observed in ZIKV-infected pregnant women carrying fetuses with fetal growth-associated malformations. Notably, infants with congenital central nervous system deformities had significantly higher levels of interleukin 18 and IP-10 but lower levels of hepatocyte growth factor than those without such abnormalities born to ZIKV-infected mothers.

CONCLUSIONS

This study identified several key markers for the control of ZIKV pathogenesis. This will allow a better understanding of the molecular mechanisms of ZIKV infection in patients.

摘要

背景

寨卡病毒(ZIKV)感染与不同程度的临床结果相关,范围从轻微皮疹和发热到严重的神经并发症和先天性畸形。

方法

我们调查了95名来自巴西坎皮纳斯的急性ZIKV感染成年患者的临床和免疫反应,重点关注免疫介质谱。这些患者包括6名在本研究过程中后来分娩的孕妇。住院期间记录临床观察结果。使用基于微珠的多重免疫测定法定量45种免疫介质的水平。

结果

11.6%的患者有神经并发症,88.4%表现为皮疹和发热的轻症。几种免疫介质在ZIKV感染患者中特别高,白细胞介素10、干扰素γ诱导蛋白10(IP-10)和肝细胞生长因子的水平在有或没有神经并发症的患者之间有所不同。有趣的是,在携带与胎儿生长相关畸形胎儿的ZIKV感染孕妇中观察到白细胞介素22、单核细胞趋化蛋白1、TNF-α和IP-10的水平较高。值得注意的是,患有先天性中枢神经系统畸形的婴儿白细胞介素18和IP-10水平明显高于ZIKV感染母亲所生无此类异常的婴儿,但肝细胞生长因子水平较低。

结论

本研究确定了控制ZIKV发病机制的几个关键标志物。这将有助于更好地理解ZIKV感染患者的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d104/5853428/fdb2ba9ad90e/jix26101.jpg

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