Quantitative metabolome profiling reveals the involvement of the kynurenine pathway in influenza-associated encephalopathy

Yuka Torii, Yoshihiko Kawano, Hajime Sato, Kazunori Sasaki, Tamaki Fujimori, Jun ichi Kawada, Osamu Takikawa, Chai K. Lim, Gilles J. Guillemin, Yoshiaki Ohashi, Yoshinori Ito*

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Introduction: Influenza-associated encephalopathy is a serious complication of influenza and is the most common form of acute encephalitis/encephalopathy in Japan. The number of reports from other countries is increasing, reflecting international recognition and concern. Objectives: Identification of a specific biomarker could provide important clues about the pathophysiology of influenza-associated encephalopathy. Methods: During the 2009–2011 flu seasons, 34 pediatric patients hospitalized with influenza complications, including influenza-associated encephalopathy, were enrolled in the study. Serum samples were collected during the acute and convalescent phases of disease. Patients were classified into encephalopathy (n = 12) and non-encephalopathy (n = 22) groups. Serum metabolites were identified and quantified by capillary electrophoresis coupled with time-of-flight mass spectrometry. Quantified data were evaluated for comparative analysis. Subsequently, a total of 55 patients with or without encephalopathy were enrolled for absolute quantification of serum kynurenine and quinolinic acid. Results: Based on m/z values and migration times, 136 metabolites were identified in serum samples. During the acute phase of disease, three metabolites (succinic acid, undecanoic acid, and kynurenine) were significantly higher, and two other metabolites (decanoic acid and cystine) were significantly lower, in the encephalopathy group compared to the non-encephalopathy group (p = 0.012, 0.022, 0.044, 0.038, 0.046, respectively). In a larger patient group, serum kynurenine and its downstream product in tryptophan metabolism, quinolinic acid, a known neurotoxin, were significantly higher in the encephalopathy than the non-encephalopathy without febrile seizure group. Conclusion: Comprehensive metabolite profiles revealed five metabolites as potential biomarkers for influenza-associated encephalopathy; the tryptophan–kynurenine metabolic process could be associated with its pathophysiology.

Original languageEnglish
Article number84
Pages (from-to)1-9
Number of pages9
JournalMetabolomics
Volume12
Issue number5
DOIs
Publication statusPublished - 1 May 2016

Keywords

  • Encephalopathy
  • Influenza
  • Kynurenine
  • Metabolome
  • Quinolinic acid

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