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Observational Study
. 2022 Jan 12:12:774043.
doi: 10.3389/fimmu.2021.774043. eCollection 2021.

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

Jeffrey A Tornheim  1   2 , Mandar Paradkar  3 , Henry Zhao  4 , Vandana Kulkarni  3 , Neeta Pradhan  3 , Aarti Kinikar  5 , Anju Kagal  5 , Nikhil Gupte  2   3 , Vidya Mave  2   3 , Amita Gupta  1   2   6 , Petros C Karakousis  1   2   6
Affiliations
Observational Study

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

Jeffrey A Tornheim et al. Front Immunol. .

Abstract

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.

Keywords: biomarker; diagnostics; metabolomics (OMICS); pediatric tuberculosis; transcriptomics.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Changes in Metabolite Abundance and Transcript Expression Over Time Among Cases and Controls. Abundance of each biomarker of interest is expressed as a boxplot with a smoothed regression line in red indicating change over time at each visit, indicated by month of visit. Shading around each red line indicates 95% confidence around the trend. The top row of panels contains plots for cases and the bottom row of panels indicates plots for controls. Each column represents a distinct biomarker with IDO-1 transcript expression in the left column, followed by tryptophan abundance, kynurenine abundance, and the kynurenine/tryptophan (K/T) ratio moving from left to right. None of these biomarkers demonstrated a significant change over duration of follow-up among cases or controls.
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