title: Soluble TREM-2 in cerebrospinal fluid from patients with multiple sclerosis treated with natalizumab or mitoxantrone.
abstract: Microglia-mediated proteolysis of the triggering receptor expressed on myeloid cells-2 (TREM-2) produces soluble TREM-2 (sTREM-2) that can be measured in cerebrospinal fluid (CSF) samples. Loss-of-function mutations in TREM2 or in the gene encoding its adaptor protein cause the rare Nasu-Hakola disease (NHD). Multiple sclerosis (MS) is an autoimmune disease that in common with NHD is characterized by demyelination and microglial activation.
  
  
  
  To investigate the potential utility of sTREM-2 as a biomarker for MS and to follow treatment effects.
  
  
  
  sTREM-2 was analyzed in CSF samples from subjects with MS (N = 59); relapsing-remitting MS (RRMS) (N = 36), secondary progressive MS (SPMS) (N = 20) and primary progressive MS (PPMS) (N = 3), and controls (N = 27). CSF levels of sTREM-2 were also assessed before and after treatment of patients with natalizumab or mitoxantrone.
  
  
  
  CSF levels of sTREM-2 were significantly increased in patients with RRMS, SPMS, and PPMS compared with controls. After natalizumab treatment, the levels of sTREM-2 were normalized to control levels. The levels of sTREM-2 were also reduced after mitoxantrone treatment.
  
  
  
  Increased CSF levels of sTREM-2, a new marker of microglial activation, in MS and normalization upon treatment with either natalizumab or mitoxantrone support a role for microglial activation in active MS.
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden annika.ohrfelt@neuro.gu.se.
authors.forename: Annika
authors.initials: A
authors.lastname: Öhrfelt
authors.affiliation: Department of Neurology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Axelsson
authors.affiliation: Department of Neurology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Clas
authors.initials: C
authors.lastname: Malmeström
authors.affiliation: Department of Neurology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Lenka
authors.initials: L
authors.lastname: Novakova
authors.affiliation: UCL Institute of Neurology, University College London (UCL), London, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Heslegrave
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Department of Neurology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Lycke
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden/UCL Institute of Neurology, University College London (UCL), London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000134:cerebrospinal fluid* / Q000187:drug effects*; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000494:pharmacology*; D020528:Multiple Sclerosis, Chronic Progressive / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D000069442:Natalizumab / Q000008:administration & dosage / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000187:drug effects*; D059005:Topoisomerase II Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D007155:Immunologic Factors; D008562:Membrane Glycoproteins; D000069442:Natalizumab; D011971:Receptors, Immunologic; C498715:TREM2 protein, human; D059005:Topoisomerase II Inhibitors; D008942:Mitoxantrone
keywords: TREM-2; cerebrospinal fluid; immunosuppressive therapy; microglia; mitoxantrone; multiple sclerosis; natalizumab