TY - JOUR
T1 - The Kynurenine/Tryptophan Ratio Is a Sensitive Biomarker for the Diagnosis of Pediatric Tuberculosis Among Indian Children
AU - for the CTRIUMPH RePORT India Study Team
AU - Tornheim, Jeffrey A.
AU - Paradkar, Mandar
AU - Zhao, Henry
AU - Kulkarni, Vandana
AU - Pradhan, Neeta
AU - Kinikar, Aarti
AU - Kagal, Anju
AU - Gupte, Nikhil
AU - Mave, Vidya
AU - Gupta, Amita
AU - Karakousis, Petros C.
N1 - Funding Information:
CTRIUMPH was supported by the NIH/DBT RePORT India Consortium with funding in whole or in part from the Government of India’s (GOI) Department of Biotechnology (DBT), the Indian Council of Medical Research (ICMR), the United States National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID), Office of AIDS Research (OAR), and distributed in part by CRDF Global. This publication was made possible by support from the Johns Hopkins University Center for AIDS Research (NIH P30AI094189). AG, NG, and VM were also supported by NIH/ NIAID under award number UM1AI069465. PK was supported by NIH/NIAID (K24AI143447) and the U.S. Civilian Research & Development Foundation distributed by CRDF Global. JT was supported by NIH/NIAID (K23AI135102 and R21AI122922), the NIH/Fogarty Global Health Fellows Program Consortium (R25TW009340), and the Johns Hopkins University School of Medicine Clinician Scientist Career Development Award.
Publisher Copyright:
Copyright © 2022 Tornheim, Paradkar, Zhao, Kulkarni, Pradhan, Kinikar, Kagal, Gupte, Mave, Gupta and Karakousis.
PY - 2022/1/12
Y1 - 2022/1/12
N2 - Objectives: Pediatric tuberculosis (TB) remains difficult to diagnose. The plasma kynurenine to tryptophan ratio (K/T ratio) is a potential biomarker for TB diagnosis and treatment response but has not been assessed in children. Methods: We performed a targeted diagnostic accuracy analysis of four biomarkers: kynurenine abundance, tryptophan abundance, the K/T ratio, and IDO-1 gene expression. Data were obtained from transcriptome and metabolome profiling of children with confirmed tuberculosis and age- and sex-matched uninfected household contacts of pulmonary tuberculosis patients. Each biomarker was assessed as a baseline diagnostic and in response to successful TB treatment. Results: Despite non-significant between-group differences in unbiased analysis, the K/T ratio achieved an area under the receiver operator characteristic curve (AUC) of 0.667 and 81.5% sensitivity for TB diagnosis. Kynurenine, tryptophan, and IDO-1 demonstrated diagnostic AUCs of 0.667, 0.602, and 0.463, respectively. None of these biomarkers demonstrated high AUCs for treatment response. The AUC of the K/T ratio was lower than biomarkers identified in unbiased analysis, but improved sensitivity over existing commercial assays for pediatric TB diagnosis. Conclusions: Plasma kynurenine and the K/T ratio may be useful biomarkers for pediatric TB. Ongoing studies in geographically diverse populations will determine optimal use of these biomarkers worldwide.
AB - Objectives: Pediatric tuberculosis (TB) remains difficult to diagnose. The plasma kynurenine to tryptophan ratio (K/T ratio) is a potential biomarker for TB diagnosis and treatment response but has not been assessed in children. Methods: We performed a targeted diagnostic accuracy analysis of four biomarkers: kynurenine abundance, tryptophan abundance, the K/T ratio, and IDO-1 gene expression. Data were obtained from transcriptome and metabolome profiling of children with confirmed tuberculosis and age- and sex-matched uninfected household contacts of pulmonary tuberculosis patients. Each biomarker was assessed as a baseline diagnostic and in response to successful TB treatment. Results: Despite non-significant between-group differences in unbiased analysis, the K/T ratio achieved an area under the receiver operator characteristic curve (AUC) of 0.667 and 81.5% sensitivity for TB diagnosis. Kynurenine, tryptophan, and IDO-1 demonstrated diagnostic AUCs of 0.667, 0.602, and 0.463, respectively. None of these biomarkers demonstrated high AUCs for treatment response. The AUC of the K/T ratio was lower than biomarkers identified in unbiased analysis, but improved sensitivity over existing commercial assays for pediatric TB diagnosis. Conclusions: Plasma kynurenine and the K/T ratio may be useful biomarkers for pediatric TB. Ongoing studies in geographically diverse populations will determine optimal use of these biomarkers worldwide.
KW - biomarker
KW - diagnostics
KW - metabolomics (OMICS)
KW - pediatric tuberculosis
KW - transcriptomics
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U2 - 10.3389/fimmu.2021.774043
DO - 10.3389/fimmu.2021.774043
M3 - Article
C2 - 35095848
AN - SCOPUS:85123440734
SN - 1664-3224
VL - 12
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 774043
ER -