title: Cerebrospinal fluid lipocalin 2 in patients with clinically isolated syndromes and early multiple sclerosis.
abstract: Lipocalin 2 (LCN2) may be involved in the immunopathogenesis of multiple sclerosis (MS) and might further impact on iron homoeostasis. Brain iron accumulates in MS; however, the association to iron-related proteins is still unsolved.
  
  
  
  To investigate cerebrospinal fluid (CSF) and serum LCN2, transferrin (Trf) and ferritin in early MS in relation to disease evolution and longitudinal brain iron accumulation.
  
  
  
  We analysed CSF and serum LCN2 by enzyme-linked immunosorbent assay (ELISA) and Trf and ferritin by nephelometry in 55 patients (45 clinically isolated syndrome (CIS), 10 MS, median clinical follow-up 4.8 years) and 63 controls. In patients, we assessed sub-cortical grey matter iron by 3T magnetic resonance imaging (MRI) R2* relaxometry (median imaging follow-up 2.2 years).
  
  
  
  Compared to controls serum (p < 0.01), CSF (p < 0.001) LCN2 and CSF Trf (p < 0.001) levels were reduced in the patients. CSF LCN2 correlated with CSF Trf (r = 0.5, p < 0.001). In clinically stable patients, CSF LCN2 levels correlated with basal ganglia iron accumulation (r = 0.5, p < 0.05). In CIS, higher CSF LCN2 levels were associated with conversion to clinically definite MS (p < 0.05).
  
  
  
  We demonstrate altered LCN2 regulation in early MS and provide first evidence for this to be possibly linked to both clinical MS activity and iron accumulation in the basal ganglia.
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria michael.khalil@medunigraz.at.
authors.forename: M
authors.initials: M
authors.lastname: Khalil
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Renner
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Langkammer
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria/Division of Neuroradiology, Department of Radiology, Medical University of Graz, Graz, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Enzinger
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Ropele
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Stojakovic
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Scharnagl
authors.affiliation: Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Bachmaier
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Pichler
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: J J
authors.initials: JJ
authors.lastname: Archelos
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Fuchs
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Seifert-Held
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: F
authors.initials: F
authors.lastname: Fazekas
mesh_terms: D000328:Adult; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000378:metabolism*; D003711:Demyelinating Diseases / Q000097:blood / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007501:Iron / Q000378:metabolism*; D000071068:Lipocalin-2 / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging
chemical_list: C489506:LCN2 protein, human; D000071068:Lipocalin-2; D007501:Iron
keywords: 3T MRI; Lipocalin 2; biomarker; brain iron; cerebrospinal fluid; clinically isolated syndrome; multiple sclerosis