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

Payam Nahid, Erin Bliven-Sizemore, Leah G. Jarlsberg, Mary A. De Groote, John L. Johnson, Grace Muzanyi, Melissa Engle, Marc Weiner, Nebojsa Janjic, David G. Sterling, Urs A. Ochsner

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34 Scopus citations

Abstract

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. 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. Results 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). 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.

Original languageEnglish (US)
Pages (from-to)187-196
Number of pages10
JournalTuberculosis
Volume94
Issue number3
DOIs
StatePublished - May 2014

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Keywords

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

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Nahid, P., Bliven-Sizemore, E., Jarlsberg, L. G., De Groote, M. A., Johnson, J. L., Muzanyi, G., Engle, M., Weiner, M., Janjic, N., Sterling, D. G., & Ochsner, U. A. (2014). Aptamer-based proteomic signature of intensive phase treatment response in pulmonary tuberculosis. Tuberculosis, 94(3), 187-196. https://doi.org/10.1016/j.tube.2014.01.006