Circulating cell-free RNA in blood as a host response biomarker for detection of tuberculosis

Adrienne Chang, Conor J. Loy, Daniel Eweis-LaBolle, Joan S. Lenz, Amy Steadman, Alfred Andgrama, Nguyen Viet Nhung, Charles Yu, William Worodria, Claudia M. Denkinger, Payam Nahid, Adithya Cattamanchi and Iwijn De Vlaminck ()
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Adrienne Chang: Cornell University
Conor J. Loy: Cornell University
Daniel Eweis-LaBolle: Cornell University
Joan S. Lenz: Cornell University
Amy Steadman: Inc.
Alfred Andgrama: World Alliance for Lung and Intensive Care Medicine in Uganda
Nguyen Viet Nhung: National Lung Hospital
Charles Yu: De La Salle Medical and Health Sciences Institute
William Worodria: World Alliance for Lung and Intensive Care Medicine in Uganda
Claudia M. Denkinger: University Hospital Heidelberg & German Center of Infection Research
Payam Nahid: University of California San Francisco
Adithya Cattamanchi: University of California San Francisco
Iwijn De Vlaminck: Cornell University

Nature Communications, 2024, vol. 15, issue 1, 1-8

Abstract: Abstract Tuberculosis (TB) remains a leading cause of death from an infectious disease worldwide, partly due to a lack of effective strategies to screen and triage individuals with potential TB. Whole blood RNA signatures have been tested as biomarkers for TB, but have failed to meet the World Health Organization’s (WHO) optimal target product profiles (TPP). Here, we use RNA sequencing and machine-learning to investigate the utility of plasma cell-free RNA (cfRNA) as a host-response biomarker for TB in cohorts from Uganda, Vietnam and Philippines. We report a 6-gene cfRNA signature, which differentiates TB-positive and TB-negative individuals with AUC = 0.95, 0.92, and 0.95 in test, training and validation, respectively. This signature meets WHO TPPs (sensitivity: 97.1% [95% CI: 80.9-100%], specificity: 85.2% [95% CI: 72.4-100%]) regardless of geographic location, sample collection method and HIV status. Overall, our results identify plasma cfRNA as a promising host response biomarker to diagnose TB.

Date: 2024
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DOI: 10.1038/s41467-024-49245-6

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