Aptamer-based proteomic signature of intensive phase treatment response in pulmonary tuberculosis.
Aptamer-based proteomic signature of intensive phase treatment response in pulmonary tuberculosis.
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DOI：
10.1016/j.tube.2014.01.006
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Ochsner UA
中科院分区：
文献类型：
--
作者：
Nahid P;Bliven-Sizemore E;Jarlsberg LG;De Groote MA;Johnson JL;Muzanyi G;Engle M;Weiner M;Janjic N;Sterling DG;Ochsner UA
结核病的治疗需要更有效、持续时间更短的新药物方案。准确、定量、非培养的治疗反应标志物的鉴定将提高二期结核病药物试验的效率。在一种无偏倚的生物标志物发现方法中，我们应用了一种高度多元的、基于适体体的蛋白质组学技术，分析了来自乌干达坎帕拉的39名肺结核患者在基线和治疗8周后收集的血清样本，这些患者参加了疾病控制和预防中心（CDC）结核病试验联盟的2B期治疗试验。我们鉴定了与8周培养状态相关的蛋白表达差异，包括凝血因子V、SAA、XPNPEP1、PSME1、il - 11r α、HSP70、半乳糖凝集素-8、α2-抗凝血蛋白、ECM1、YES、IGFBP-1、CATZ、BGN、LYNB和IL-7。在应答者和缓慢应答者之间存在差异变化的标志物包括连接素样蛋白2、EphA1 （Ephrin type-A受体1）、gp130、CNDP1、TGF-b RIII、MRC2、ADAM9和CDON。结合8周培养状态相关指标建立logistic回归模型，ROC曲线AUC=0.96，灵敏度=0.95，特异性=0.90。其他标记显示反应者和慢反应者（连接蛋白样蛋白）之间的差异变化，或与培养转化时间（KLRK1）相关。参与凝血级联、中性粒细胞活性、免疫、炎症和组织重塑的血清蛋白被发现与结核病治疗反应有关。在这项初步研究中，确定了一种定量的、非基于培养的、预测8周培养状态的五标记签名。
New drug regimens of greater efficacy and shorter duration are needed for tuberculosis (TB) treatment. The identification of accurate, quantitative, non-culture based markers of treatment response would improve the efficiency of Phase 2 TB drug testing. In an unbiased biomarker discovery approach, we applied a highly multiplexed, aptamer-based, proteomic technology to analyze serum samples collected at baseline and after 8 weeks of treatment from 39 patients with pulmonary TB from Kampala, Uganda enrolled in a Centers for Disease Control and Prevention (CDC) TB Trials Consortium Phase 2B treatment trial. We identified protein expression differences associated with 8-week culture status, including Coagulation Factor V, SAA, XPNPEP1, PSME1, IL-11 Rα, HSP70, Galectin-8, α2-Antiplasmin, ECM1, YES, IGFBP-1, CATZ, BGN, LYNB, and IL-7. Markers noted to have differential changes between responders and slow-responders included nectin-like protein 2, EphA1 (Ephrin type-A receptor 1), gp130, CNDP1, TGF-b RIII, MRC2, ADAM9, and CDON. A logistic regression model combining markers associated with 8-week culture status revealed an ROC curve with AUC=0.96, sensitivity=0.95 and specificity=0.90. Additional markers showed differential changes between responders and slow-responders (nectin-like protein), or correlated with time-to-culture-conversion (KLRK1). Serum proteins involved in the coagulation cascade, neutrophil activity, immunity, inflammation, and tissue remodeling were found to be associated with TB treatment response. A quantitative, non-culture based, five-marker signature predictive of 8-week culture status was identified in this pilot study.
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影响因子：
3.7
作者：
Gold L;Ayers D;Bertino J;Bock C;Bock A;Brody EN;Carter J;Dalby AB;Eaton BE;Fitzwater T;Flather D;Forbes A;Foreman T;Fowler C;Gawande B;Goss M;Gunn M;Gupta S;Halladay D;Heil J;Heilig J;Hicke B;Husar G;Janjic N;Jarvis T;Jennings S;Katilius E;Keeney TR;Kim N;Koch TH;Kraemer S;Kroiss L;Le N;Levine D;Lindsey W;Lollo B;Mayfield W;Mehan M;Mehler R;Nelson SK;Nelson M;Nieuwlandt D;Nikrad M;Ochsner U;Ostroff RM;Otis M;Parker T;Pietrasiewicz S;Resnicow DI;Rohloff J;Sanders G;Sattin S;Schneider D;Singer B;Stanton M;Sterkel A;Stewart A;Stratford S;Vaught JD;Vrkljan M;Walker JJ;Watrobka M;Waugh S;Weiss A;Wilcox SK;Wolfson A;Wolk SK;Zhang C;Zichi D
通讯作者：
Zichi D
DOI：
10.1164/rccm.201105-0827ws
发表时间：
2011-10-15
影响因子：
24.7
作者：
Nahid, Payam;Saukkonen, Jussi;Burman, William
通讯作者：
Burman, William
影响因子：
8.6
作者：
Nemeth, Johannes;Winkler, Heide-Maria;Winkler, Stefan
通讯作者：
Winkler, Stefan
影响因子：
5.4
作者：
Gold, Larry;Walker, Jeffrey J.;Williams, Stephen
通讯作者：
Williams, Stephen
DOI：
10.1016/s0140-6736(06)69342-2
发表时间：
2006-09-16
期刊：
Lancet (London, England)
影响因子：
--
作者：
Agranoff D;Fernandez-Reyes D;Papadopoulos MC;Rojas SA;Herbster M;Loosemore A;Tarelli E;Sheldon J;Schwenk A;Pollok R;Rayner CF;Krishna S
通讯作者：
Krishna S