Plasma host protein biomarkers correlating with increasing Mycobacterium tuberculosis infection activity prior to tuberculosis diagnosis in people living with HIV.
Plasma host protein biomarkers correlating with increasing Mycobacterium tuberculosis infection activity prior to tuberculosis diagnosis in people living with HIV.
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DOI：
10.1016/j.ebiom.2021.103787
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发表时间：
2022-01
期刊：
影响因子：
11.1
通讯作者：
Achkar JM
中科院分区：
文献类型：
--
作者：
Singer SN;Ndumnego OC;Kim RS;Ndung'u T;Anastos K;French A;Churchyard G;Paramithiothis E;Kasprowicz VO;Achkar JM
迫切需要与无症状个体中结核分枝杆菌感染活动/负担相关的生物标志物来识别和治疗那些发展为活动性结核病(TB)的最高风险人群。我们的主要目标是确定在艾滋病毒携带者(PLHIV)患者发生结核病之前随时间变化的血浆宿主蛋白生物标记物。利用多重MRM-MS，我们研究了纵向(每隔3-6个月)收集和储存南非(SA)和美国队列中确诊为结核病的PLHIV患者的血浆中宿主蛋白的表达。我们对蛋白质进行了时间趋势和判别分析，为了确保临床相关性，我们进一步将结核病诊断时的蛋白质水平与干扰素-伽马释放试验(IGRA；SA)或结核菌素皮肤试验(TST；US)阳性和阴性的无结核病队列受试者进行了比较。分别对SA和US探查数据进行分析。在控制了10%的误发率后，我们在SA(n=30)和美国(n=24)发病结核病受试者中鉴定了15种蛋白质，它们都从两年前到结核病诊断时发生了变化，并且在结核病诊断时与非结核病受试者相比有显著差异(p<；0.01)。CD14、A2GL、NID1、SCTM1和A1AG1 5个蛋白在两个队列之间重叠。此外，经过交叉验证，由5-12个蛋白质组成的小组能够在诊断前两年预测结核病。宿主蛋白可作为增加结核分枝杆菌感染活动/负担、早期结核病和预测PLHIV中结核病发展的生物标志物。NIH/NIAID AI117927、AI146329和AI127173到JMA。
Biomarkers correlating with Mycobacterium tuberculosis infection activity/burden in asymptomatic individuals are urgently needed to identify and treat those at highest risk for developing active tuberculosis (TB). Our main objective was to identify plasma host protein biomarkers that change over time prior to developing TB in people living with HIV (PLHIV). Using multiplex MRM-MS, we investigated host protein expressions from 2 years before until time of TB diagnosis in longitudinally collected (every 3-6 months) and stored plasma from PLHIV with incident TB, identified within a South African (SA) and US cohort. We performed temporal trend and discriminant analyses for proteins, and, to assure clinical relevance, we further compared protein levels at TB diagnosis to interferon-gamma release assay (IGRA; SA) or tuberculin-skin test (TST; US) positive and negative cohort subjects without TB. SA and US exploratory data were analyzed separately. We identified 15 proteins in the SA (n=30) and 10 in the US (n=24) incident TB subjects which both changed from 2 years prior until time of TB diagnosis after controlling for 10% false discovery rate, and were significantly different at time of TB diagnosis compared to non-TB subjects (p<0.01). Five proteins, CD14, A2GL, NID1, SCTM1, and A1AG1, overlapped between both cohorts. Furthermore, after cross-validation, panels of 5 – 12 proteins were able to predict TB up to two years before diagnosis. Host proteins can be biomarkers for increasing Mycobacterium tuberculosis infection activity/burden, incipient TB, and predict TB development in PLHIV. NIH/NIAID AI117927, AI146329, and AI127173 to JMA.
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影响因子：
158.5
作者：
Churchyard, Gavin J.;Fielding, Katherine L.;Grant, Alison D.
通讯作者：
Grant, Alison D.
影响因子：
11.8
作者：
Brumme, Zabrina;Wang, Bingxia;Losina, Elena
通讯作者：
Losina, Elena
影响因子：
5.4
作者：
Barkan, SE;Melnick, SL;Feldman, J
通讯作者：
Feldman, J
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
5.2
作者：
Darboe, Fatoumatta;Mbandi, Stanley Kimbung;Erasmus, Mzwandile
通讯作者：
Erasmus, Mzwandile