title: Serum biomarker gMS-Classifier2: predicting conversion to clinically definite multiple sclerosis.
abstract: BACKGROUND
  Anti-glycan antibodies can be found in autoimmune diseases. IgM against glycan P63 was identified in clinically isolated syndromes (CIS) and included in gMS-Classifier2, an algorithm designed with the aim of identifying patients at risk of a second demyelinating attack.
  
  
  OBJECTIVE
  To determine the value of gMS-Classifier2 as an early and independent predictor of conversion to clinically definite multiple sclerosis (CDMS).
  
  
  METHODS
  Data were prospectively acquired from a CIS cohort. gMS-Classifier2 was determined in patients first seen between 1995 and 2007 with ≥ two 200 µL serum aliquots (N = 249). The primary endpoint was time to conversion to CDMS at two years, the factor tested was gMS-Classifier2 status (positive/negative) or units; other exploratory time points were 5 years and total time of follow-up.
  
  
  RESULTS
  Seventy-five patients (30.1%) were gMS-Classifier2 positive. Conversion to CDMS occurred in 31/75 (41.3%) of positive and 45/174 (25.9%) of negative patients (p = 0.017) at two years. Median time to CDMS was 37.8 months (95% CI 10.4-65.3) for positive and 83.9 months (95% CI 57.5-110.5) for negative patients. gMS-Classifier2 status predicted conversion to CDMS within two years of follow-up (HR = 1.8, 95% CI 1.1-2.8; p = 0.014). gMS-Classifier2 units were also independent predictors when tested with either Barkhof criteria and OCB (HR = 1.2, CI 1.0-1.5, p = 0.020) or with T2 lesions and OCB (HR = 1.3, CI 1.1-1.5, p = 0.008). Similar results were obtained at 5 years of follow-up. Discrimination measures showed a significant change in the area under the curve (ΔAUC) when adding gMS-Classifier2 to a model with either Barkhof criteria (ΔAUC 0.0415, p = 0.012) or number of T2 lesions (ΔAUC 0.0467, p = 0.009), but not when OCB were added to these models.
  
  
  CONCLUSIONS
  gMS-Classifier2 is an independent predictor of early conversion to CDMS and could be of clinical relevance, particularly in cases in which OCB are not available.
authors.affiliation: Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Vall d'Hebron University Hospital and Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Georgina
authors.initials: G
authors.lastname: Arrambide
authors.forename: Carmen
authors.initials: C
authors.lastname: Espejo
authors.forename: Jennifer
authors.initials: J
authors.lastname: Yarden
authors.forename: Ella
authors.initials: E
authors.lastname: Fire
authors.forename: Larissa
authors.initials: L
authors.lastname: Spector
authors.forename: Nir
authors.initials: N
authors.lastname: Dotan
authors.forename: Avinoam
authors.initials: A
authors.lastname: Dukler
authors.forename: Alex
authors.initials: A
authors.lastname: Rovira
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.forename: Mar
authors.initials: M
authors.lastname: Tintore
mesh_terms: D000328:Adult; D000465:Algorithms; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000032:analysis*; D003711:Demyelinating Diseases / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood* / Q000503:physiopathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007075:Immunoglobulin M
references.citation: Mult Scler. 2009 Apr;15(4):422-30
references.pmid: 19324980
references.citation: J Clin Epidemiol. 1993 Jan;46(1):85-93
references.pmid: 8433118
references.citation: Curr Opin Neurol. 2011 Jun;24(3):230-7
references.pmid: 21499098
references.citation: Inflamm Bowel Dis. 2010 Aug;16(8):1367-75
references.pmid: 20024902
references.citation: Glycobiology. 2004 Feb;14(2):197-203
references.pmid: 14638630
references.citation: J Immunol. 2006 Feb 1;176(3):1525-33
references.pmid: 16424181
references.citation: J Neurol Sci. 2006 May 15;244(1-2):59-68
references.pmid: 16480743
references.citation: Arch Neurol. 2006 Apr;63(4):614-9
references.pmid: 16606781
references.citation: J Clin Lab Anal. 1998;12(6):363-70
references.pmid: 9850188
references.citation: J Neuroimmunol. 2009 Dec 10;217(1-2):95-101
references.pmid: 19879655
references.citation: Neurology. 2008 Mar 25;70(13 Pt 2):1079-83
references.pmid: 17881717
references.citation: Neurobiol Dis. 2009 Aug;35(2):117-27
references.pmid: 19426803
references.citation: Ann Neurol. 1992 Jun;31(6):677-9
references.pmid: 1514781
references.citation: Am J Ophthalmol. 2005 Jun;139(6):1101-8
references.pmid: 15953446
references.citation: Ann Neurol. 1983 Mar;13(3):227-31
references.pmid: 6847134
references.citation: Acta Neurol Scand. 1992 Sep;86(3):317-22
references.pmid: 1414254
references.citation: Clin Diagn Lab Immunol. 1996 Mar;3(2):219-26
references.pmid: 8991640
references.citation: Eur J Neurol. 2010 Jun 1;17(6):852-60
references.pmid: 20100231
references.citation: Lancet Neurol. 2005 Jan;4(1):32-41
references.pmid: 15620855
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10273-8
references.pmid: 16014416
references.citation: BMC Med Res Methodol. 2011 Jan 28;11:13
references.pmid: 21276237
references.citation: Ann Neurol. 2011 Feb;69(2):292-302
references.pmid: 21387374
references.citation: J Clin Lab Anal. 1998;12(6):371-7
references.pmid: 9850189
references.citation: Glycobiology. 2003 Nov;13(11):749-54
references.pmid: 12851287
references.citation: Zentralbl Bakteriol. 1960 Jul;179:433-6
references.pmid: 13854323
references.citation: Stat Med. 2013 Apr 30;32(9):1467-82
references.pmid: 23296397
references.citation: Nat Immunol. 2008 Jun;9(6):593-601
references.pmid: 18490910
references.citation: J Allergy Clin Immunol. 2005 Aug;116(2):453-9
references.pmid: 16083805
references.citation: Mult Scler. 2012 Jul;18(7):966-73
references.pmid: 22183938
references.citation: Brain. 2008 Mar;131(Pt 3):808-17
references.pmid: 18234696
references.citation: Ann Neurol. 1991 Feb;29(2):147-51
references.pmid: 2012384
references.citation: Neurology. 2006 Sep 26;67(6):968-72
references.pmid: 17000962
references.citation: J Neuroimmunol. 2005 Oct;167(1-2):131-7
references.pmid: 16051375
references.citation: Neurobiol Dis. 2006 Dec;24(3):484-91
references.pmid: 17005408