Aptamer-based proteomic signature of intensive phase treatment response in pulmonary tuberculosis

作者：Nahid Payam^*; Bliven Sizemore Erin; Jarl**erg Leah G; De Groote Mary A; Johnson John L; Muzanyi Grace; Engle Melissa; Weiner Marc; Janjic Nebojsa; Sterling David G; Ochsner Urs A

来源：Tuberculosis, 2014, 94(3): 187-196.

DOI：10.1016/j.tube.2014.01.006

• Tuberculosis
• Treatment response
• Biomarkers
• Proteomics
• Multiplex analysis
• SOMAscan
• Logistic regression model

Background: 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. %26lt;br%26gt;Methods: 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. %26lt;br%26gt;Results: We identified protein expression differences associated with 8-week culture status, including Coagulation Factor V, SAA, XPNPEP1, PSME1, IL-11 R alpha, HSP70, Galectin-8, alpha 2-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). %26lt;br%26gt;Conclusions: 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.

• 出版日期2014-5