PLoS ONE (Jan 2013)

Serum biomarker gMS-Classifier2: predicting conversion to clinically definite multiple sclerosis.

  • Georgina Arrambide,
  • Carmen Espejo,
  • Jennifer Yarden,
  • Ella Fire,
  • Larissa Spector,
  • Nir Dotan,
  • Avinoam Dukler,
  • Alex Rovira,
  • Xavier Montalban,
  • Mar Tintore

DOI
https://doi.org/10.1371/journal.pone.0059953
Journal volume & issue
Vol. 8, no. 3
p. e59953

Abstract

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BackgroundAnti-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.ObjectiveTo determine the value of gMS-Classifier2 as an early and independent predictor of conversion to clinically definite multiple sclerosis (CDMS).MethodsData 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.ResultsSeventy-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.ConclusionsgMS-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.