By Neil Osterweil, Senior Associate Editor, MedPage Today
Reviewed by Rubeen K. Israni, M.D., Fellow, Renal-Electrolyte and Hypertension Division, University of Pennsylvania School of Medicine
January 24, 2007
BASEL, Switzerland, Jan. 24 -- Contrary to a previous report, the presence in the blood of two types of antibodies to myelin is not diagnostic of multiple sclerosis, investigators here reported.
Action Points
Explain to interested patients that the demyelinating disease multiple sclerosis is diagnosed according to clinical symptoms and MRI evidence of brain lesions. Contrary to findings of an earlier research group, this study suggests that the presence of antibodies to myelin are not diagnostic of MS or of MS risk.
Nor does the presence of the antibodies indicate a risk of progression to clinically definite MS, found Jens Kuhle, M.D., of University Hospital here, along with European and Canadian investigators.
Although other investigators have found that the patients with serum antibodies against myelin oligodendrocyte glycoprotein and myelin basic protein were at increased risk for MS, Dr. Kuhle and colleagues could find no such link, they reported in the Jan. 25 issue of the New England Journal of Medicine.
In a study of 462 patients with a first clinical event suggestive of MS and at least two silent brain lesions on MRI, there was no association between serum levels of either of two antimyelin antibody types and risk of progression to clinically definite MS.
"Our results strongly suggest that antimyelin antibodies have no role in the diagnosis of multiple sclerosis or in the identification of patients at high risk for the development of clinically definite disease," the investigators wrote. "Alternatively, there may be a role for such antibodies, but we may need more sophisticated methods to detect them."
The investigators used serum samples from the 462 patients enrolled in the BENEFIT study, a randomized double-blind, placebo-controlled, phase III trial evaluating Betaseron (interferon beta-1b) at a dose of 250 μg subcutaneously every other day in patients with a first clinical episode suggestive of MS, and at least two clinically silent lesions detect on MRI scans of the brain.
They measured serum anti-myelin oligodendrocyte glycoprotein and anti-myelin basic protein at baseline by Western blot analysis, and compared the results with the time and rate of progression to clinically definite multiple sclerosis, or to a diagnosis of multiple sclerosis as defined by an international panel (the McDonald criteria).
The patients had regular visits for the assessment of neurologic impairment and for MRI before treatment and at months three, six, nine, 12, 18, and 24.
They used chi square analysis and the Kruskal-Wallis test to compare the baseline characteristics of the patients in the placebo and treatment groups according to antibody status.
They used Kaplan-Meier analysis to calculate cumulative risk of progression to clinically definite multiple sclerosis, or multiple sclerosis as defined by the McDonald criteria), and created Cox proportional-hazards models adjusted for potential confounding variables to assess whether antibody status predicted the development of MS.
They controlled for age, sex, use of corticosteroid treatment for the first event, the effect of treatment with Betaseron, multifocal or monofocal disease presentation, and the number of gadolinium-enhancing lesions on T1-weighted MRI scans and the number of hyperintense lesions on T2-weighted scans.
During the two-year study, 150 patients (32%) were diagnosed with clinically definite multiple sclerosis, and 331 (72%) were diagnosed with MS according to the McDonald criteria.
The authors found that "there was no increase in the risk of clinically definite multiple sclerosis or of multiple sclerosis according to the McDonald criteria among patients who were positive for anti-myelin oligodendrocyte glycoprotein antibodies, anti-myelin basic protein antibodies, or both," the authors wrote.
"This was true for both IgM and IgG antibodies not only in the total study population but also in all subgroups analyzed: patients receiving placebo or interferon beta-1b, patients with positive cerebrospinal fluid findings, patients who had received corticosteroid treatment, and patients with shorter or longer intervals between the initial clinical event and blood collection."
"Finally, we were unable to confirm the previously reported association between the number of lesions seen on gadolinium-enhanced MRI brain scans and the anti-myelin oligodendrocyte glycoprotein or anti-myelin basic protein antibody status," they added.
They noted that time of blood sample collection -- for example, within a few days of the first manifestation of clinical disease and before corticosteroids -- could have had an influence on the results.
They also acknowledged that the follow-up in the study, which was limited to two years, may have been too short to detect a positive correlation between the antibodies and MS.
"However, in view of the number of patients in whom clinically definite multiple sclerosis or multiple sclerosis according to the Mc-Donald criteria was diagnosed during the two-year follow-up period, a major change in the results with longer follow-up would be highly improbable, " they wrote.
The study was supported in part by Schering AG, which sponsored the BENEFIT study, and by a grant from the Swiss Multiple Sclerosis Society.
No potential conflicts of interest relevant to the study were reported by the authors.
