The Kynurenine/Tryptophan Ratio Is a Sensitive Biomarker for the Diagnosis of Pediatric Tuberculosis Among Indian Children

Frontiers in Immunology

Aarti Kinikar¹  Anju Kagal¹  Mandar Paradkar²  Vandana Kulkarni²  Neeta Pradhan²  Vidya Mave²  Nikhil Gupte²  Jeffrey A. Tornheim³  Petros C. Karakousis⁵  Amita Gupta⁵  Henry Zhao⁶ 

[1] Byramjee Jeejeebhoy Government Medical College, Pune, India;Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site, Pune, India;Center for Clinical Global Health Education, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States;Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States;Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States;Johns Hopkins University, Baltimore, MD, United States;

关键词: biomarker;    transcriptomics;    metabolomics (OMICS);    diagnostics;    pediatric tuberculosis;   

DOI  :  10.3389/fimmu.2021.774043

来源: DOAJ

【 摘 要 】

ObjectivesPediatric 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.MethodsWe 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.ResultsDespite 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.ConclusionsPlasma 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.

【 授权许可】

Unknown