Kynurenine pathway metabolomics predicts and provides mechanistic insight into multiple sclerosis progression

Chai K. Lim*, Ayse Bilgin, David B. Lovejoy, Vanessa Tan, Sonia Bustamante, Bruce V. Taylor, Alban Bessede, Bruce J. Brew, Gilles J. Guillemin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

89 Citations (Scopus)
21 Downloads (Pure)

Abstract

Activation of the kynurenine pathway (KP) of tryptophan metabolism results from chronic inflammation and is known to exacerbate progression of neurodegenerative disease. To gain insights into the links between inflammation, the KP and multiple sclerosis (MS) pathogenesis, we investigated the KP metabolomics profile of MS patients. Most significantly, we found aberrant levels of two key KP metabolites, kynurenic acid (KA) and quinolinic acid (QA). The balance between these metabolites is important as it determines overall excitotoxic activity at the N-methyl-D-Aspartate (NMDA) receptor. We also identified that serum KP metabolic signatures in patients can discriminate clinical MS subtypes with high sensitivity and specificity. A C5.0 Decision Tree classification model discriminated the clinical subtypes of MS with a sensitivity of 91%. After validation in another independent cohort, sensitivity was maintained at 85%. Collectively, our studies suggest that abnormalities in the KP may be associated with the switch from early-mild stage MS to debilitating progressive forms of MS and that analysis of KP metabolites in MS patient serum may have application as MS disease biomarkers.

Original languageEnglish
Article number41473
Pages (from-to)1-9
Number of pages9
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 3 Feb 2017

Bibliographical note

Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • QUINOLINIC ACID
  • INDOLEAMINE 2,3-DIOXYGENASE
  • MASS-SPECTROMETRY
  • DENDRITIC CELLS
  • DISEASE COURSE
  • HUMAN PLASMA
  • METABOLISM
  • TRYPTOPHAN
  • ENCEPHALOMYELITIS
  • EXCITOTOXICITY

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