Achkar Jacqueline M, Cortes Laetitia, Croteau Pascal, Yanofsky Corey, Mentinova Marija, Rajotte Isabelle, Schirm Michael, Zhou Yiyong, Junqueira-Kipnis Ana Paula, Kasprowicz Victoria O, Larsen Michelle, Allard René, Hunter Joanna, Paramithiotis Eustache
Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA ; Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.
Caprion Proteomics Inc., 201 President-Kennedy Ave., Montreal H2X 3Y7, Quebec, Canada.
EBioMedicine. 2015 Jul 30;2(9):1160-8. doi: 10.1016/j.ebiom.2015.07.039. eCollection 2015 Sep.
Biomarkers for active tuberculosis (TB) are urgently needed to improve rapid TB diagnosis. The objective of this study was to identify serum protein expression changes associated with TB but not latent Mycobacterium tuberculosis infection (LTBI), uninfected states, or respiratory diseases other than TB (ORD). Serum samples from 209 HIV uninfected (HIV(-)) and co-infected (HIV(+)) individuals were studied. In the discovery phase samples were analyzed via liquid chromatography and mass spectrometry, and in the verification phase biologically independent samples were analyzed via a multiplex multiple reaction monitoring mass spectrometry (MRM-MS) assay. Compared to LTBI and ORD, host proteins were significantly differentially expressed in TB, and involved in the immune response, tissue repair, and lipid metabolism. Biomarker panels whose composition differed according to HIV status, and consisted of 8 host proteins in HIV(-) individuals (CD14, SEPP1, SELL, TNXB, LUM, PEPD, QSOX1, COMP, APOC1), or 10 host proteins in HIV(+) individuals (CD14, SEPP1, PGLYRP2, PFN1, VASN, CPN2, TAGLN2, IGFBP6), respectively, distinguished TB from ORD with excellent accuracy (AUC = 0.96 for HIV(-) TB, 0.95 for HIV(+) TB). These results warrant validation in larger studies but provide promise that host protein biomarkers could be the basis for a rapid, blood-based test for TB.
迫切需要用于活动性肺结核（TB）的生物标志物来改善肺结核的快速诊断。本研究的目的是确定与肺结核相关，但与潜伏性结核分枝杆菌感染（LTBI）、未感染状态或除肺结核之外的呼吸道疾病（ORD）无关的血清蛋白表达变化。研究了209名未感染人类免疫缺陷病毒（HIV）（HIV（-））和合并感染HIV（HIV（+））个体的血清样本。在发现阶段，通过液相色谱和质谱分析样本，在验证阶段，通过多重多反应监测质谱（MRM-MS）分析生物独立样本。与LTBI和ORD相比，宿主蛋白在肺结核中显著差异表达，并参与免疫反应、组织修复和脂质代谢。生物标志物组根据HIV状态的不同而组成不同，在HIV（-）个体中由8种宿主蛋白组成（CD14、硒蛋白P1、淋巴细胞功能相关抗原1、腱生蛋白X、层黏连蛋白、肽酶D、醌氧化还原酶1、软骨寡聚基质蛋白、载脂蛋白C1），在HIV（+）个体中由10种宿主蛋白组成（CD14、硒蛋白P1、肽聚糖识别蛋白2、丝切蛋白1、血管星状蛋白、羧肽酶N2、原肌球蛋白2、胰岛素样生长因子结合蛋白6），分别以优异的准确性区分肺结核与ORD（HIV（-）肺结核的曲线下面积[AUC]=0.96，HIV（+）肺结核的AUC=0.95）。这些结果值得在更大规模的研究中进行验证，但表明宿主蛋白生物标志物有望成为基于血液的肺结核快速检测的基础。
