1. Serum biomarker gMS-Classifier2: predicting conversion to clinically definite multiple sclerosis
- Author
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Arrambide, Georgina, Espejo, Carmen, Yarden, Jennifer, Fire, Ella, Spector, Larissa, Dotan, Nir, Dukler, Avinoam, Rovira, Alex, Montalban, Xavier, Tintoré, Mar, and Universitat Autònoma de Barcelona
- Subjects
Blood Glucose ,Male ,Multivariate analysis ,Time Factors ,Neuroimmunology ,Gastroenterology ,Clinical endpoint ,Longitudinal Studies ,Prospective Studies ,Prospective cohort study ,Multidisciplinary ,Area under the curve ,Prognosis ,Neurology ,Area Under Curve ,Cohort ,Disease Progression ,Medicine ,Female ,Algorithms ,Research Article ,Adult ,medicine.medical_specialty ,Multiple Sclerosis ,Science ,Immunoglobulins ,Autoimmune Diseases ,Immune Activation ,Internal medicine ,medicine ,Humans ,Clinical significance ,Immunoassays ,Proportional Hazards Models ,Inflammation ,business.industry ,Proportional hazards model ,Multiple sclerosis ,Immunity ,Immunologic Subspecialties ,medicine.disease ,Demyelinating Disorders ,Surgery ,Gene Expression Regulation ,Immunoglobulin M ,ROC Curve ,Humoral Immunity ,Immunologic Techniques ,Clinical Immunology ,business ,Biomarkers ,Demyelinating Diseases - Abstract
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.
- Published
- 2013