title: Soluble serum VCAM-1, whole blood mRNA expression and treatment response in natalizumab-treated multiple sclerosis.
abstract: BACKGROUND
  Natalizumab reduces disease activity in multiple sclerosis (MS). Natalizumab binds to the very late antigen-4 and inhibits vascular cell adhesion molecule-1 (VCAM-1)-mediated transmigration of immune cells across the blood-brain-barrier. This is associated with decreased serum concentrations of soluble (s)VCAM-1 and an altered composition of immune cell-subsets in the blood.
  
  
  OBJECTIVE
  We aimed to examine if sVCAM-1 serum concentrations and whole blood mRNA expression levels of immune activation biomarkers is associated with disease activity in natalizumab-treated MS-patients.
  
  
  METHODS
  sVCAM-1 serum concentrations and whole blood mRNA expression were measured in blood samples from untreated RRMS-patients and from two independent groups of natalizumab-treated patients.
  
  
  RESULTS
  sVCAM-1 serum concentrations and whole blood expression of HLX1 and IL1B mRNA were lower, whereas expression of EBI3 mRNA was higher in natalizumab-treated MS-patients. Five genes were differentially expressed in clinically unstable natalizumab-treated MS-patients in the discovery but not in the validation group.
  
  
  CONCLUSIONS
  Decreased serum concentrations of sVCAM-1 and altered whole blood mRNA expression levels of a panel of immunomarkers, associated with natalizumab-treatment, are not sensitive markers of MS disease activity. However, decreased expression of pro-inflammatory HLX1 and IL1B and increased expression of immunoregulatory EBI3 may indicate a less pathogenic immune activation status in natalizumab-treated MS.
authors.affiliation: Danish Multiple Sclerosis Center, Department of neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Electronic address: Eva.rosa.petersen@regionh.dk.
authors.forename: E R
authors.initials: ER
authors.lastname: Petersen
authors.affiliation: Danish Multiple Sclerosis Center, Department of neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: H B
authors.initials: HB
authors.lastname: Søndergaard
authors.affiliation: Danish Multiple Sclerosis Center, Department of neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: A B
authors.initials: AB
authors.lastname: Oturai
authors.affiliation: Danish Multiple Sclerosis Center, Department of neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peh
authors.initials: P
authors.lastname: Jensen
authors.affiliation: Danish Multiple Sclerosis Center, Department of neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: P S
authors.initials: PS
authors.lastname: Sorensen
authors.affiliation: Danish Multiple Sclerosis Center, Department of neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Sellebjerg
authors.affiliation: Danish Multiple Sclerosis Center, Department of neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Börnsen
mesh_terms: D000328:Adult; D054316:Biomarkers, Pharmacological / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D018398:Homeodomain Proteins / Q000097:blood; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000097:blood; D007378:Interleukins / Q000097:blood; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000097:blood; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D000069442:Natalizumab / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000097:blood*; D013997:Time Factors; D014157:Transcription Factors / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
chemical_list: D054316:Biomarkers, Pharmacological; C097732:EBI3 protein, human; D005938:Glucocorticoids; C084058:HLX protein, human; D018398:Homeodomain Proteins; C508585:IL1B protein, human; D007155:Immunologic Factors; D053583:Interleukin-1beta; D007378:Interleukins; D015778:Minor Histocompatibility Antigens; D000069442:Natalizumab; D012333:RNA, Messenger; D014157:Transcription Factors; D019010:Vascular Cell Adhesion Molecule-1
keywords: Disease modifying therapies; Immunology; Multiple Sclerosis; Natalizumab; Relapsing/remitting; SVCAM-1