Predictive nature of IgM anti-α-glucose serum biomarker for relapse activity and EDSS progression in CIS patients: a BENEFIT study analysis

• Published in: Multiple sclerosis 2012-07, Vol.18 (7), p.966-973
• Main Authors: Freedman, MS, Metzig, C, Kappos, L, Polman, CH, Edan, G, Hartung, H-P, Miller, DH, Montalban, X, Yarden, J, Spector, L, Fire, E, Dotan, N, Schwenke, S, Lanius, V, Sandbrink, R, Pohl, C
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Autoantibodies - blood; Autoantigens - immunology; Biological and medical sciences; Biomarkers - blood; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Demyelinating Diseases - blood; Demyelinating Diseases - drug therapy; Demyelinating Diseases - immunology; Disease Progression; Female; Glucose - immunology; Humans; Immunoglobulin M - blood; Immunologic Factors - therapeutic use; Interferon-beta - therapeutic use; Male; Medical sciences; Middle Aged; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Prognosis; Recurrence; Research Papers; Young Adult
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1177/1352458511432327

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.