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

PLoS One

Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Vall d'Hebron University Hospital and Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.

Published: January 2014

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3610690PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0059953PLOS

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Article Synopsis
  • Early treatment with immunomodulating therapy improves short-term clinical outcomes in multiple sclerosis (MS) patients, reducing the risk of conversion to clinically definite MS (CDMS) by 30.5%.
  • In a study of patients with clinically isolated syndrome (CIS), those who received early treatment demonstrated fewer relapses and maintained stable disability over 15 years compared to a delayed treatment group.
  • By the 15-year mark, 66.3% of patients treated early remained employed, further indicating the benefits of starting treatment early in the disease course.
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