Proteome-Scale Antibody Responses and Outcome of Mycobacterium tuberculosis Infection in Nonhuman Primates and in Tuberculosis Patients
Proteome-Scale Antibody Responses and Outcome of Mycobacterium tuberculosis Infection in Nonhuman Primates and in Tuberculosis Patients
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DOI：
10.1093/infdis/jis421
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发表时间：
2012-09-01
影响因子：
6.4
通讯作者：
Gennaro, Maria L.
中科院分区：
文献类型：
--
作者：
Kunnath-Velayudhan, Shajo;Davidow, Amy L.;Gennaro, Maria L.
背景。需要从潜伏结核分枝杆菌感染到活动性结核进展的生物标志物。通过高通量、蛋白质组尺度的血清学研究，我们评估了猕猴和人感染结果与抗体反应之间的相关性。方法：用代表不同感染结果的猕猴系列血清和结核病嫌疑人的单点人类血清对结核分枝杆菌蛋白质组微阵列进行了探测。通过计算Z分数和相关P值来分析荧光强度数据。用多项式回归分析猕猴抗体反应的时间变化。结果：猕猴结果组表现出不同的抗体谱：潜伏感染时早期、短暂的抗体反应，活动性和再活动性疾病时抗体稳定增加。在人类中，抗体水平和反应蛋白数量随着细菌负荷的增加而增加。结论：猕猴和人类数据的整合揭示了抗体反应与结果相关的动态特性，并为转化研究提供了可操作的发现。其中包括抗体反应检测急性感染和临床前结核病的潜力，以及鉴定结核病细菌负荷谱的血清诊断蛋白。
Background. Biomarkers of progression from latent Mycobacterium tuberculosis infection to active tuberculosis are needed. We assessed correlations between infection outcome and antibody responses in macaques and humans by high-throughput, proteome-scale serological studies.Methods.Mycobacterium tuberculosis proteome microarrays were probed with serial sera from macaques representing various infection outcomes and with single-point human sera from tuberculosis suspects. Fluorescence intensity data were analyzed by calculating Z scores and associated P values. Temporal changes in macaque antibody responses were analyzed by polynomial regression. Correlations between human responses and sputum bacillary burden were assessed by quantile and hurdle regression.Results.Macaque outcome groups exhibited distinct antibody profiles: early, transient responses in latent infection and stable antibody increase in active and reactivation disease. In humans, antibody levels and reactive protein numbers increased with bacillary burden. Responses to a subset of 10 proteins were more tightly associated with disease state than reactivity to the broader reactive proteome.Conclusions.Integration of macaque and human data reveals dynamic properties of antibody responses in relation to outcome and leads to actionable findings for translational research. These include the potential of antibody responses to detect acute infection and preclinical tuberculosis and to identify serodiagnostic proteins for the spectrum of bacillary burden in tuberculosis.