title: Disease Type- and Status-Specific Alteration of CSF Metabolome Coordinated with Clinical Parameters in Inflammatory Demyelinating Diseases of CNS.
abstract: Central nervous system (CNS) inflammatory demyelinating diseases (IDDs) are a group of disorders with different aetiologies, characterized by inflammatory lesions. These disorders include multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and idiopathic transverse myelitis (ITM). Differential diagnosis of the CNS IDDs still remains challenging due to frequent overlap of clinical and radiological manifestation, leading to increased demands for new biomarker discovery. Since cerebrospinal fluid (CSF) metabolites may reflect the status of CNS tissues and provide an interfacial linkage between blood and CNS tissues, we explored multi-component biomarker for different IDDs from CSF samples using gas chromatography mass spectrometry-based metabolite profiling coupled to multiplex bioinformatics approach. We successfully constructed the single model with multiple metabolite variables in coordinated regression with clinical characteristics, expanded disability status scale, oligoclonal bands, and protein levels. The multi-composite biomarker simultaneously discriminated four different immune statuses (a total of 145 samples; 54 MS, 49 NMOSD, 30 ITM, and 12 normal controls). Furthermore, systematic characterization of transitional metabolic modulation identified relapse-associated metabolites and proposed insights into the disease network underlying type-specific metabolic dysfunctionality. The comparative analysis revealed the lipids, 1-monopalmitin and 1-monostearin were common indicative for MS, NMOSD, and ITM whereas fatty acids were specific for the relapse identified in all types of IDDs.
authors.affiliation: The Department of Bio and Fermentation Convergence Technology, BK21 PLUS project, Kookmin University, Seoul, Korea.
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: The Department of Neurology, Research Institute and Hospital of the National Cancer Center, Goyang, Korea.
authors.forename: In Hye
authors.initials: IH
authors.lastname: Jeong
authors.affiliation: The Department of Neurology, Research Institute and Hospital of the National Cancer Center, Goyang, Korea.
authors.forename: Byung Soo
authors.initials: BS
authors.lastname: Kong
authors.affiliation: The Department of Bio and Fermentation Convergence Technology, BK21 PLUS project, Kookmin University, Seoul, Korea.
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: The Department of Biotechnology, Graduate School, Korea University, Seoul, Korea.
authors.forename: Kyoung Heon
authors.initials: KH
authors.lastname: Kim
authors.affiliation: The Department of Bio and Fermentation Convergence Technology, BK21 PLUS project, Kookmin University, Seoul, Korea.
authors.forename: Do Yup
authors.initials: DY
authors.lastname: Lee
authors.affiliation: The Department of Neurology, Research Institute and Hospital of the National Cancer Center, Goyang, Korea.
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D019540:Area Under Curve; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology*; D003711:Demyelinating Diseases / Q000134:cerebrospinal fluid* / Q000150:complications*; D016002:Discriminant Analysis; D006801:Humans; D007249:Inflammation / Q000134:cerebrospinal fluid* / Q000150:complications*; D016018:Least-Squares Analysis; D055442:Metabolome; D015233:Models, Statistical; D015999:Multivariate Analysis; D012372:ROC Curve; D012008:Recurrence
chemical_list: D015415:Biomarkers