1200. Quantitative Metabolome Profiling Reveals Novel Potential Biomarkers in Influenza-Associated Encephalopathy
Session: Oral Abstract Session: Biomarkers of Infectious Diseases
Saturday, October 5, 2013: 8:30 AM
Room: The Moscone Center: 300
Background: Influenza-associated encephalopathy (IAE) is a serious complication of influenza, showing high mortality and morbidity rates. Cases of IAE have mostly been reported from Japan since the 1990s, and the number of reports is increasing among other countries, reflecting international recognition and concern. However, the pathology of IAE has not been fully clarified. Metabolome profiling, an approach capable of describing an entire set of metabolites, has become an effective measure for discovering new biomarkers associated with disease pathophysiology. Serum samples from IAE patients were analyzed using this approach.

Methods: During 2009-2011 flu seasons, 34 pediatric patients hospitalized with influenza complications including IAE were enrolled in the study. Serum samples were collected at the acute and convalescent phases of disease. Patients were classified into an IAE group (n=12) and a non-IAE group (n=22). Serum metabolites were identified and quantified by capillary electrophoresis coupled with time-of-flight mass spectrometry. Quantified data were evaluated for comparative analysis. Welch’s t test and the paired t test were used to assess the significance of differences among groups or among phases.

Results: Based on m/z values and migration time, 174 metabolites were identified in serum samples. Levels of three metabolites (succinic acid, kynurenine, and undecanoic acid) were significantly higher, and those of two other metabolites (decanoic acid and cystine) were significantly lower in the IAE group than in the non-IAE group at the acute phase of disease (p=0.012, 0.044, 0.022, 0.022, 0.046, respectively). Kynurenine and its downstream product in tryptophan metabolism, quinolinic acid, were analyzed because quinolinic acid is known as a neurotoxin. Although quinolinic acid levels were not significantly elevated in the IAE group, a correlation was seen between kynurenine and quinolinic acid (p<0.001, r=0.654).

Conclusion: Metabolite profiles revealed five metabolites as potential biomarkers for IAE. The tryptophan-kynurenine metabolic process could be associated with the pathophysiology of IAE.

Yuka Torii, MD1, Yoshihiko Kawano, MD1, Hajime Sato2, Tamaki Fujimori, PhD.2, Kazunori Sasaki2, Jun-Ichi Kawada, MD1, Yoshiaki Ohashi, PhD2 and Yoshinori Ito, MD1, (1)Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan, (2)Human Metabolome Technologies, Inc., Tsuruoka, Japan

Disclosures:

Y. Torii, Human Metabolome Technologies, Inc.: Collaborator, Research grant

Y. Kawano, Human Metabolome Technologies, Inc.: Collaborator, Research grant

H. Sato, Human Metabolome Technologies, Inc.: Collaborator, Research grant

T. Fujimori, Human Metabolome Technologies, Inc.: Collaborator, Research grant

K. Sasaki, Human Metabolome Technologies, Inc.: Collaborator, Research grant

J. I. Kawada, Human Metabolome Technologies, Inc.: Collaborator, Research grant

Y. Ohashi, Human Metabolome Technologies, Inc.: Collaborator, Research grant

Y. Ito, Human Metabolome Technologies, Inc.: Collaborator, Research grant

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