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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

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posted on 2023-06-09, 13:59 authored by Sarah L Pett, Ken M Kunisaki, Deborah Wentoworth, Timothy J Griffin, Ioannis Kalomenidis, Raquel Nahra, Rocio Montejano Sanchez, Shane W Hodgson, Kiat Ruxrungtham, Dominic Dwyer, Richard T Davey, Chris H Wendy, Melanie NewportMelanie Newport, INSIGHT FLU003 Plus Study Group
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. CLINICALTRIALSGOV IDENTIFIER: NCT01056185.

History

Publication status

  • Published

File Version

  • Published version

Journal

Open Forum Infectious Diseases

ISSN

2328-8957

Publisher

Oxford University Press

Issue

1

Volume

5

Page range

1-9

Department affiliated with

  • Global Health and Infection Publications

Research groups affiliated with

  • Wellcome Trust Brighton and Sussex Centre for Global Health Research Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-06-28

First Open Access (FOA) Date

2018-06-28

First Compliant Deposit (FCD) Date

2018-06-27

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