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Increased Indoleamine-2,3-Dioxygenase Activity Is Associated With Poor Clinical Outcome in Adults Hospitalized With Influenza in the INSIGHT FLU003Plus Study

Pett, SL; Kunisaki, KM; Wentworth, D; Griffin, TJ; Kalomenidis, I; Nahra, R; Montejano Sanchez, R; ... INSIGHT FLU003 Plus Study Group, .; + view all (2018) Increased Indoleamine-2,3-Dioxygenase Activity Is Associated With Poor Clinical Outcome in Adults Hospitalized With Influenza in the INSIGHT FLU003Plus Study. Open Forum Infectious Diseases , 5 (1) , Article ofx228. 10.1093/ofid/ofx228. Green open access

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Abstract

BACKGROUND: Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections. METHODS: We performed a case-control (1:2; age and sex matched) analysis of adults hospitalized with influenza A(H1N1)pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression. RESULTS: We included 32 cases and 64 controls with a median age of 52 years; 41% were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mM/M; IQR, 0.13–0.40) than controls (0.12; IQR, 0.09–0.17; P ≤ .001). When divided into tertiles, 59% of cases vs 20% of controls had KT ratios in the highest tertile (0.21–0.84 mM/M). When adjusted for symptom duration, the odds ratio for disease progression for those in the highest vs lowest tertiles of KT ratio was 9.94 (95% CI, 2.25–43.90). CONCLUSIONS: High KT ratio was associated with poor outcome in adults hospitalized with influenza A(H1N1)pdm09. The clinical utility of this biomarker in this setting merits further exploration. CLINICALTRIALS.GOV IDENTIFIER: NCT01056185.

Type: Article
Title: Increased Indoleamine-2,3-Dioxygenase Activity Is Associated With Poor Clinical Outcome in Adults Hospitalized With Influenza in the INSIGHT FLU003Plus Study
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/ofid/ofx228
Publisher version: https://doi.org/10.1093/ofid/ofx228
Language: English
Additional information: Copyright © The Author(s) 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
Keywords: influenza; indoleamine-2,3-dioxygenase; kynurenine; outcome; tryptophan
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health
URI: https://discovery.ucl.ac.uk/id/eprint/10042369
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