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Tuberculosis (Edinb). 2014 May;94(3):187-96. doi: 10.1016/j.tube.2014.01.006. Epub 2014 Feb 7.

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

Author information

1
Pulmonary and Critical Care Medicine, University of California, San Francisco at San Francisco General Hospital, 1001 Potrero Ave, 5K1, San Francisco, CA 94110, USA. Electronic address: pnahid@ucsf.edu.
2
Centers for Disease Control and Prevention, Division of Tuberculosis Elimination, 1600 Clifton Rd., NE, MS E10, Atlanta, GA 30333, USA.
3
Pulmonary and Critical Care Medicine, University of California, San Francisco at San Francisco General Hospital, 1001 Potrero Ave, 5K1, San Francisco, CA 94110, USA.
4
Department of Microbiology, Immunology and Pathology, Colorado State University, Campus Box 1682, Fort Collins, CO 80523, USA; SomaLogic, Inc., 2945 Wilderness Place, Boulder, CO 80301, USA.
5
Tuberculosis Research Unit, Division of Infectious Diseases, Case Western Reserve University, Cleveland, OH, USA; Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda.
6
Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda.
7
Department of Medicine, Division of Infectious Diseases, University of Texas Health Science Center, San Antonio, TX, USA.
8
SomaLogic, Inc., 2945 Wilderness Place, Boulder, CO 80301, USA.
9
SomaLogic, Inc., 2945 Wilderness Place, Boulder, CO 80301, USA. Electronic address: uochsner@somalogic.com.

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.

KEYWORDS:

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

PMID:
24629635
PMCID:
PMC4028389
DOI:
10.1016/j.tube.2014.01.006
[Indexed for MEDLINE]
Free PMC Article

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