July 9, 2003
Laurie Barclay, MD
Medscape Medical News
Antimyelin antibodies may be useful as a predictor of clinical multiple sclerosis after a first demyelinating event, according to the results of a study published in the July 10 issue of the New England Journal of Medicine. The editorialist agrees that once these results are confirmed, this test may be important for counseling and management of these patients.
"Most patients with multiple sclerosis initially present with a clinically isolated syndrome," write Thomas Berger, MD, from the University of Innsbruck in Austria, and colleagues. "Despite the fact that clinically definite multiple sclerosis will develop in up to 80% of these patients, the course of the disease is unpredictable at its onset and requires long-term observation or repeated magnetic resonance imaging (MRI)."
Dr. Berger's group performed brain MRI, cerebrospinal fluid (CSF) analysis for oligoclonal bands, and Western blot analysis of serum samples for anti-myelin oligodendrocyte glycoprotein (MOG) and anti-myelin basic protein (MBP) in 103 patients with a clinically isolated syndrome.
Anti-MOG and anti-MBP antibodies predicted more frequent and earlier relapses. Of 39 seronegative patients, nine (23%) had a relapse, and time to relapse was 45 ± 13.7 months. Of 22 patients with anti-MOG and anti-MBP, 21 (95%) relapsed, and mean time to relapse was 7.5 ± 4.4 months. Of 42 patients with only anti-MOG, 35 (83%) relapsed within 14.6 ± 9.6 months (P < .001 for both comparisons with antibody-seronegative patients.)
Compared with seronegative patients, the adjusted hazard ratio for development of clinically definite multiple sclerosis was 76.5 (95% confidence interval [CI], 20.6 - 284.6) for patients with both antimyelin antibodies, and 31.6 (95% CI, 9.5 - 104.5) among patients with only anti-MOG.
The authors stress that they cannot prove whether antibodies against MOG and MBP have demyelinating capacity or whether they represent an epiphenomenon of myelin destruction.
"Analysis of antibodies against MOG and MBP in patients with a clinically isolated syndrome is a rapid, inexpensive, and precise method for the prediction of early conversion to clinically definite multiple sclerosis," Dr. Berger's team write. "This finding may be important for the counseling and care of patients with a first demyelinating event suggestive of multiple sclerosis."
Several authors report financial relationships with Biogen, Medacorp, Serono, Schering, Pfizer, and/or Aventis.
In an accompanying editorial, Jack P. Antel, MD, and Amit Bar-Or, MD, from the Montreal Neurological Institute of McGill University, agree that these findings, "once confirmed, will improve the quality of the diagnostic and prognostic information that can be used to guide treatment decisions, enhance insight into the pathogenesis of the disease, and possibly identify subgroups of patients for whom B-cell-directed therapies would be indicated."
In an accompanying article, Hartmut Wekerle, MD, and Reinhart Hohlfeld, MD, from the Max-Planck Institute for Neurobiology in Martinsned, Germany, discuss molecular mimicry in multiple sclerosis. They suggest that more selective therapies using altered peptide ligands derived from autoantigenic peptides might reduce activity of autoaggressive T cells while leaving the remaining immune system intact.
"Preliminary clinical trials involving an altered peptide ligand derived from MBP indicated that low and intermediate doses of the ligand have some promise, whereas high doses stimulated allergic reactions and activated, rather than muted, the activity of MBP-specific T cells," they write. "A better understanding of the mechanisms of molecular mimicry should help to explain these puzzling observations and perhaps contribute to the development of new peptide ligands for the treatment of multiple sclerosis."
N Engl J Med. 2003;349:107-109, 139-145, 185-186
Reviewed by Gary D. Vogin, MD
Laurie Barclay, MD Writer for Medscape Medical News
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