1326. Quantitative Metabolome Profiling Reveals Novel Potential Biomarkers in Human Herpesvirus 6 Encephalopathy
Session: Poster Abstract Session: Biomarkers and Correlates of Protection
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • 2013_IDSA_poster_Kawano_final_1024x768.pdf (1.5 MB)
  • Background: Primary human herpesvirus (HHV)-6 infects the majority of human populations worldwide and causes roseola (exanthema subitum). Occasionally, primary HHV-6 infection shows accompanying neurological complications, including febrile seizures and acute encephalopathy. In Japan, HHV-6 is the second most common pathogen causing acute sporadic encephalitis/encephalopathy in children. However, the pathology of HHV-6 encephalopathy remains unclear. Metabolomics is a remarkable method that searches for disease-specific biomarkers by analyzing the comprehensive kinetics of metabolites, resulting in an assessment of disease pathophysiology. Metabolome profiling was investigated for identifying novel biomarkers in HHV-6 encephalopathy.

    Methods: Nine patients with HHV-6 encephalopathy, 11 with HHV-6 febrile seizure (FS), nine with non-HHV-6 FS (control-FS) and seven with non-HHV-6 infection without FS (control) were enrolled in this study. Serum samples in the acute phase of the disease were collected, and metabolites were identified and quantified by capillary electrophoresis coupled with time-of-flight mass spectrometry. These data were evaluated for statistical significance using Welch’s t test and analysis of variance.

    Results: Based on m/z values and migration time, 159 candidates were identified in the serum samples. Eight metabolites showed higher levels in the HHV-6 encephalopathy group than in the HHV-6 FS group. Among those eight metabolites, the p-values for kynurenine and sarcosine were 0.023 and 0.029, respectively. Levels of kynurenine and sarcosine were higher in the HHV-6 encephalopathy group than in the control group (p=0.006 and p=0.0025, respectively). In 110 of the 159 candidates, levels of 56 metabolites, including kynurenine and sarcosine were quantified. We further analyzed kynurenine and its downstream product; quinolinic acid, because quinolinic acid is a known neurotoxin. Quinolinic acid tended to be higher in the HHV-6 encephalopathy group than in the HHV-6 FS group (p=0.054).

    Conclusion: Metabolite profiles revealed two metabolites as potential biomarkers for HHV-6 encephalopathy. While the function of sarcosine has been uncovered, the tryptophan-kynurenine metabolic process could be associated with the pathophysiology of HHV-6 encephalopathy.

    Yoshihiko Kawano, MD1, Yuka Torii, 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. Kawano, Human Metabolome Technologies, Inc.: Collaborator, Research grant

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

    H. Sato, None

    T. Fujimori, None

    K. Sasaki, None

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

    Y. Ohashi, None

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

    Findings in the abstracts are embargoed until 12:01 a.m. PST, Oct. 2nd with the exception of research findings presented at the IDWeek press conferences.