title: Predictive nature of IgM anti-α-glucose serum biomarker for relapse activity and EDSS progression in CIS patients: a BENEFIT study analysis.
abstract: BACKGROUND
  Higher serum levels of at least one of a panel of four α-glucose IgM antibodies (gMS-Classifier1) in clinically isolated syndrome (CIS) patients are associated with imminent early relapse within 2 years.
  
  
  OBJECTIVE
  The objective of this study was to determine the prognostic value of gMS-Classifier1 in a large study cohort of CIS patients.
  
  
  METHODS
  The BEtaseron(®) in Newly Emerging multiple sclerosis For Initial Treatment (BENEFIT) 5-year study was designed to evaluate the impact of early versus delayed interferon-β-1b (IFNβ-1b; Betaseron(®)) treatment in patients with a first event suggestive of multiple sclerosis (MS). Patients (n = 258, 61% of total) with a minimum of 2 ml baseline serum were eligible for the biomarker study. gMS-Classifier1 antibodies' panel (anti-GAGA2, anti-GAGA3, anti-GAGA4 and anti-GAGA6) levels were measured blinded to clinical data. Subjects were classified as either 'positive' or 'negative' according to a classification rule.
  
  
  RESULTS
  gMS-Classifier1 was not predictive for the time to clinically definite MS or time to MS according to the revised McDonald's criteria, but did significantly predict an increased risk for confirmed disability progression (log-rank test: p = 0.012).
  
  
  CONCLUSIONS
  We could not confirm previous results that gMS-Classifier1 can predict early conversion to MS in CIS. However, raised titres of these antibodies may predict early disability progression in this patient population.
authors.affiliation: Multiple Sclerosis Research Clinic, The Ottawa Hospital - General Campus, Ottawa, Ontario, Canada. mfreedman@toh.on.ca
authors.forename: M S
authors.initials: MS
authors.lastname: Freedman
authors.forename: C
authors.initials: C
authors.lastname: Metzig
authors.forename: L
authors.initials: L
authors.lastname: Kappos
authors.forename: C H
authors.initials: CH
authors.lastname: Polman
authors.forename: G
authors.initials: G
authors.lastname: Edan
authors.forename: H-P
authors.initials: HP
authors.lastname: Hartung
authors.forename: D H
authors.initials: DH
authors.lastname: Miller
authors.forename: X
authors.initials: X
authors.lastname: Montalban
authors.forename: J
authors.initials: J
authors.lastname: Yarden
authors.forename: L
authors.initials: L
authors.lastname: Spector
authors.forename: E
authors.initials: E
authors.lastname: Fire
authors.forename: N
authors.initials: N
authors.lastname: Dotan
authors.forename: S
authors.initials: S
authors.lastname: Schwenke
authors.forename: V
authors.initials: V
authors.lastname: Lanius
authors.forename: R
authors.initials: R
authors.lastname: Sandbrink
authors.forename: C
authors.initials: C
authors.lastname: Pohl
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D015415:Biomarkers / Q000097:blood*; D003711:Demyelinating Diseases / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D018450:Disease Progression; D005260:Female; D005947:Glucose / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood*; D007155:Immunologic Factors / Q000627:therapeutic use; D016899:Interferon-beta / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D007075:Immunoglobulin M; D007155:Immunologic Factors; D016899:Interferon-beta; D005947:Glucose