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 H Weiner, Nebojsa Janjic, David G. Sterling, Urs A. Ochsner

Research output: Contribution to journalArticle

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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 - 2014

Fingerprint

Pulmonary Tuberculosis
Proteomics
Tuberculosis
Galectin 2
Logistic Models
Eph Family Receptors
Interleukin-11
Insulin-Like Growth Factor Binding Protein 1
Therapeutics
Interleukin-7
Antifibrinolytic Agents
Proteins
Uganda
Factor V
Centers for Disease Control and Prevention (U.S.)
ROC Curve
Pharmaceutical Preparations
Area Under Curve
Blood Proteins
Immunity

Keywords

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

ASJC Scopus subject areas

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

Cite this

Nahid, P., Bliven-Sizemore, E., Jarlsberg, L. G., De Groote, M. A., Johnson, J. L., Muzanyi, 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

Aptamer-based proteomic signature of intensive phase treatment response in pulmonary tuberculosis. / Nahid, Payam; Bliven-Sizemore, Erin; Jarlsberg, Leah G.; De Groote, Mary A.; Johnson, John L.; Muzanyi, Grace; Engle, Melissa; Weiner, Marc H; Janjic, Nebojsa; Sterling, David G.; Ochsner, Urs A.

In: Tuberculosis, Vol. 94, No. 3, 2014, p. 187-196.

Research output: Contribution to journalArticle

Nahid, P, Bliven-Sizemore, E, Jarlsberg, LG, De Groote, MA, Johnson, JL, Muzanyi, G, Engle, M, Weiner, MH, Janjic, N, Sterling, DG & Ochsner, UA 2014, 'Aptamer-based proteomic signature of intensive phase treatment response in pulmonary tuberculosis', Tuberculosis, vol. 94, no. 3, pp. 187-196. https://doi.org/10.1016/j.tube.2014.01.006
Nahid P, Bliven-Sizemore E, Jarlsberg LG, De Groote MA, Johnson JL, Muzanyi G et al. Aptamer-based proteomic signature of intensive phase treatment response in pulmonary tuberculosis. Tuberculosis. 2014;94(3):187-196. https://doi.org/10.1016/j.tube.2014.01.006
Nahid, Payam ; Bliven-Sizemore, Erin ; Jarlsberg, Leah G. ; De Groote, Mary A. ; Johnson, John L. ; Muzanyi, Grace ; Engle, Melissa ; Weiner, Marc H ; Janjic, Nebojsa ; Sterling, David G. ; Ochsner, Urs A. / Aptamer-based proteomic signature of intensive phase treatment response in pulmonary tuberculosis. In: Tuberculosis. 2014 ; Vol. 94, No. 3. pp. 187-196.
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AU - Johnson, John L.

AU - Muzanyi, Grace

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N2 - 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.

AB - 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.

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