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出生时的免疫生物标志物可预测大型出生队列中下呼吸道感染风险

Immune Biomarkers at Birth Predict Lower Respiratory Tract Infection Risk in a Large Birth Cohort.

作者信息

Mondell Ethan, Nino Gustavo, Hong Xiumei, Wang Xiaobin, Gutierrez Maria J

机构信息

School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.

Division of Pulmonary and Sleep Medicine, Children's National Hospital, George Washington University, Washington, DC 20010, USA.

出版信息

Pathogens. 2024 Sep 5;13(9):765. doi: 10.3390/pathogens13090765.

Abstract

Lower respiratory tract infections (LRTIs) remain the leading cause of infant morbidity and mortality worldwide and affect long-term respiratory health. Identifying immunological determinants of LRTI susceptibility may help stratify disease risk and identify therapies. This study aimed to identify neonatal immunological factors predicting LRTI risk in infancy. Cord blood plasma from 191 neonates from the Boston Birth Cohort was analyzed for 28 soluble immune factors. LRTI was defined as bronchiolitis, bronchitis, or pneumonia during the first year of life. Welch's -test demonstrated significantly higher log transformed concentrations of IL-17 and IFNγ in the LRTI group compared to neonates without LRTI in the first year of life ( < 0.05). Risk associations were determined using multivariate survival models. There were 29 infants with LRTIs. High cord blood levels of IFNγ (aHR = 2.35, 95% CI 1.07-5.17), TNF-β (aHR = 2.86, 95% CI 1.27-6.47), MIP-1α (aHR = 2.82, 95% CI 1.22-6.51), and MIP-1β (aHR = 2.34, 95% CI 1.05-5.20) were associated with a higher risk of LRTIs. RANTES was associated with a lower risk (aHR = 0.43, 95% CI 0.19-0.97). Soluble immune factors linked to antiviral immunity (IFNγ) and cytokines mediating inflammatory responses (TNF-β), and cell homing (MIP-1α/b), at birth were associated with an increased risk of LRTIs during infancy.

摘要

下呼吸道感染(LRTIs)仍然是全球婴儿发病和死亡的主要原因,并影响长期呼吸健康。确定LRTI易感性的免疫决定因素可能有助于分层疾病风险并确定治疗方法。本研究旨在确定预测婴儿期LRTI风险的新生儿免疫因素。对来自波士顿出生队列的191名新生儿的脐带血血浆进行了28种可溶性免疫因子分析。LRTI定义为生命第一年的细支气管炎、支气管炎或肺炎。韦尔奇t检验表明,与生命第一年未患LRTI的新生儿相比,LRTI组中白细胞介素-17(IL-17)和干扰素γ(IFNγ)的对数转换浓度显著更高(P<0.05)。使用多变量生存模型确定风险关联。有29名婴儿患有LRTIs。脐带血中高水平的IFNγ(调整后风险比[aHR]=2.35,95%置信区间[CI]1.07-5.17)、肿瘤坏死因子-β(TNF-β,aHR=2.86,95%CI 1.27-6.47)、巨噬细胞炎性蛋白-1α(MIP-1α,aHR=2.82,95%CI 1.22-6.51)和巨噬细胞炎性蛋白-1β(MIP-1β,aHR=2.34,95%CI 1.05-5.20)与LRTIs风险较高相关。调节激活正常T细胞表达和分泌的趋化因子(RANTES)与较低风险相关(aHR=0.43,95%CI 0.19-0.97)。出生时与抗病毒免疫相关的可溶性免疫因子(IFNγ)以及介导炎症反应的细胞因子(TNF-β)和细胞归巢(MIP-1α/b)与婴儿期LRTIs风险增加相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4408/11435078/6300058e8d76/pathogens-13-00765-g001.jpg

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