title: The Urine Proteome Profile Is Different in Neuromyelitis Optica Compared to Multiple Sclerosis: A Clinical Proteome Study.
abstract: OBJECTIVE
  Inflammatory demyelinating diseases of the CNS comprise a broad spectrum of diseases like neuromyelitis optica (NMO), NMO spectrum disorders (NMO-SD) and multiple sclerosis (MS). Despite clear classification criteria, differentiation can be difficult. We hypothesized that the urine proteome may differentiate NMO from MS.
  
  
  METHODS
  The proteins in urine samples from anti-aquaporin 4 (AQP4) seropositive NMO/NMO-SD patients (n = 32), patients with MS (n = 46) and healthy subjects (HS, n = 31) were examined by quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) after trypsin digestion and iTRAQ labelling. Immunoglobulins (Ig) in the urine were validated by nephelometry in an independent cohort (n = 9-10 pr. groups).
  
  
  RESULTS
  The analysis identified a total of 1112 different proteins of which 333 were shared by all 109 subjects. Cluster analysis revealed differences in the urine proteome of NMO/NMO-SD compared to HS and MS. Principal component analysis also suggested that the NMO/NMO-SD proteome profile was useful for classification. Multivariate regression analysis revealed a 3-protein profile for the NMO/NMO-SD versus HS discrimination, a 6-protein profile for NMO/NMO-SD versus MS discrimination and an 11-protein profile for MS versus HS discrimination. All protein panels yielded highly significant ROC curves (AUC in all cases >0.85, p≤0.0002). Nephelometry confirmed the presence of increased Ig-light chains in the urine of patients with NMO/NMO-SD.
  
  
  CONCLUSIONS
  The urine proteome profile of patients with NMO/NMO-SD is different from MS and HS. This may reflect differences in the pathogenesis of NMO/NMO-SD versus MS and suggests that urine may be a potential source of biomarkers differentiating NMO/NMO-SD from MS.
authors.affiliation: Department of Neurology, Odense University Hospital, Odense, Denmark; Institute for Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Helle H
authors.initials: HH
authors.lastname: Nielsen
authors.affiliation: Center for Clinical Proteomics, Odense University Hospital, Odense, Denmark.
authors.forename: Hans C
authors.initials: HC
authors.lastname: Beck
authors.affiliation: Center for Clinical Proteomics, Odense University Hospital, Odense, Denmark.
authors.forename: Lars P
authors.initials: LP
authors.lastname: Kristensen
authors.affiliation: Department for Clinical Genetics Odense University Hospital, Odense, Denmark.
authors.forename: Mark
authors.initials: M
authors.lastname: Burton
authors.affiliation: Department of Neurology, University of Debrecen, Faculty of Medicine, Debrecen, Hungary.
authors.forename: Tunde
authors.initials: T
authors.lastname: Csepany
authors.affiliation: Department of Neurology, Semmelweis University, Budapest, Hungary.
authors.forename: Magdolna
authors.initials: M
authors.lastname: Simo
authors.affiliation: Department of Neurology, Josa Andras Teaching Hospital, Nyiregyhaza, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Dioszeghy
authors.affiliation: Department of Neurology, Odense University Hospital, Odense, Denmark; Institute for Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Tobias
authors.initials: T
authors.lastname: Sejbaek
authors.affiliation: Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Manuela
authors.initials: M
authors.lastname: Grebing
authors.affiliation: Center for Clinical Proteomics, Odense University Hospital, Odense, Denmark; Department of Autoimmunology & Biomarkers, Statens Serum Institut, Copenhagen, Denmark; Clinical Biochemistry, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Niels H H
authors.initials: NH
authors.lastname: Heegaard
authors.affiliation: Department of Neurology, Odense University Hospital, Odense, Denmark; Institute for Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Illes
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016000:Cluster Analysis; D003710:Demography; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000652:urine*; D009471:Neuromyelitis Optica / Q000652:urine*; D025341:Principal Component Analysis; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D020543:Proteome