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.
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Acknowledgments
We thank the doctors for providing samples from patients. We also thank Fumiyo Ando for technical assistance. This work was supported by Human Metabolome Technologies, Inc.
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Hajime Sato, Kazunori Sasaki, Tamaki Fujimori, and Yoshiaki Ohashi are employees of Human Metabolome Technologies, Inc. All other authors report no potential conflicts.
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The study design and purpose were approved by the institutional review board of Nagoya University and were fully explained to all patients and/or their guardians. Written informed consent was provided by study participants and/or their legal guardians prior to enrolment.
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Torii, Y., Kawano, Y., Sato, H. et al. Quantitative metabolome profiling reveals the involvement of the kynurenine pathway in influenza-associated encephalopathy. Metabolomics 12, 84 (2016). https://doi.org/10.1007/s11306-016-1011-z
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DOI: https://doi.org/10.1007/s11306-016-1011-z