title: Association of cerebrospinal fluid levels of lateral olfactory tract usher substance (LOTUS) with disease activity in multiple sclerosis.
abstract: OBJECTIVE
  Although multiple sclerosis (MS) is generally considered an autoimmune demyelinating disorder of the central nervous system, axonal degeneration through Nogo receptor-1 signaling was recently recognized as an important pathological feature. Our previous identification of lateral olfactory tract usher substance (LOTUS), an endogenous Nogo receptor-1 antagonist, prompted us to analyze the relationship between LOTUS levels of cerebrospinal fluid and the clinical course of MS to evaluate whether LOTUS could be a useful biomarker for MS.
  
  
  OBJECTIVE
  To examine variations in LOTUS concentrations in the cerebrospinal fluid of patients with MS in accordance with their clinical course.
  
  
  METHODS
  Cerebrospinal fluid samples were obtained retrospectively from normal controls (NCs; n = 27) and patients with MS (n = 40), amyotrophic lateral sclerosis (n = 22), and multiple system atrophy (n = 10) between January 1, 2008, and January 1, 2014. Patients with MS were divided into relapsing-remitting MS (RRMS; n = 30) and secondary progressive MS (n = 10). Patients with RRMS were further divided into relapse and remission groups.
  
  
  METHODS
  The LOTUS concentration in cerebropsinal fluid was quantitatively detected by immunoblotting using a specific LOTUS antibody and the concentrations compared in accordance with the patients' clinical course, such as remission and relapse groups in RRMS and secondary progressive MS.
  
  
  RESULTS
  The mean (SD) cerebrospinal fluid LOTUS concentration in the relapse group of RRMS (9.3 [3.6] µg/dL) was lower than that of NCs (19.2 [4.7] µg/dL; P < .001) whereas the level in the remission group of RRMS (19.6 [5.8] µg/dL) was similar to that of NCs. The LOTUS concentration in SPMS (6.7 [1.4] µg/dL; P < .001) was lower than that of NCs and the remission group of RRMS. The LOTUS levels in other neurodegenerative diseases, such as amyotrophic lateral sclerosis and multiple system atrophy, were normal.
  
  
  CONCLUSIONS
  Variations in LOTUS concentrations were correlated with disease activity in MS. Therefore, LOTUS concentration may be useful as a possible biomarker for MS. Low LOTUS concentrations may be possibly involved in Nogo receptor-1 signaling, which may induce axonal degeneration in the relapse phase of RRMS and secondary progressive MS.
authors.affiliation: Molecular Medical Bioscience Laboratory, Department of Medical Life Science, Yokohama City University Graduate School of Medical Life Science, Yokohama, Japan2Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicin.
authors.forename: Keita
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Molecular Medical Bioscience Laboratory, Department of Medical Life Science, Yokohama City University Graduate School of Medical Life Science, Yokohama, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kurihara
authors.affiliation: Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yume
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
authors.affiliation: Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.affiliation: Molecular Medical Bioscience Laboratory, Department of Medical Life Science, Yokohama City University Graduate School of Medical Life Science, Yokohama, Japan.
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Takei
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002555:Cerebrospinal Fluid / Q000737:chemistry; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000134:cerebrospinal fluid*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid*; D019578:Multiple System Atrophy / Q000134:cerebrospinal fluid; D009185:Myelin Proteins / Q000037:antagonists & inhibitors*; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*
chemical_list: D015415:Biomarkers; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070816:Nogo Receptor 1; C486580:RTN4R protein, human; D011956:Receptors, Cell Surface