Correspondence
Lack of Association between Antimyelin Antibodies and Progression to Multiple Sclerosis
N Engl J Med 2007; 356:1888-1889May 3, 2007
- Article
To the Editor:
Seven different studies so far have shown controversial correlations (ranging from highly significant to not significant at all) regarding the predictive value of antimyelin antibodies in patients with a clinically isolated syndrome suggestive of multiple sclerosis.1-5 To validate our initial findings1 in other populations with a clinically isolated syndrome, we provided the same antimyelin-antibody immunoblot assay for all these studies. Controversial results may thus reflect differences in study populations and designs, rather than in methods. The article by Kuhle et al. (Jan. 25 issue)3 demonstrates these differences. First, apart from antimyelin antibodies, other factors — such as a monofocal or multifocal clinical presentation, the presence or absence of oligoclonal bands in the cerebrospinal fluid, and the lesion load or number of gadolinium-enhancing lesions on magnetic resonance imaging (MRI) — lacked an association with progression to multiple sclerosis. Second, as compared with multicenter trials, single-center studies may benefit from study populations with homogenous genetic backgrounds or from well-established standard operating procedures. Finally, blood sampling within 14 days after the onset of disease, which was done in only one study,1 may limit the routine use of antimyelin antibodies as a prognostic biomarker in patients with a clinically isolated syndrome.
5 ReferencesThomas Berger, M.D.
Markus Reindl, Ph.D.
Innsbruck Medical University, A-6020 Innsbruck, Austria
thomas.berger@i-med. ac. at 1
Reindl M ,Khalil M ,Berger T . Antibodies as biological markers for pathophysiological processes in multiple sclerosis. J Neuroimmunol 2006;180:50-62
CrossRef | Web of Science | Medline2
Berger T ,Rubner P ,Schautzer F , et al. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med 2003;349:139-145
Full Text | Web of Science | Medline3
Kuhle J ,Pohl C ,Mehling M , et al. Lack of association between antimyelin antibodies and progression to multiple sclerosis. N Engl J Med 2007;356:371-378
Full Text | Web of Science | Medline4
Pelayo R ,Tintore M ,Montalban X , et al. Antimyelin antibodies with no progression to multiple sclerosis. N Engl J Med 2007;356:426-428
Full Text | Web of Science | Medline5
Tomassini V, De Giglio L, Reindl M, et al. Anti-myelin antibodies predict the clinical outcome after a first episode suggestive of MS. Mult Scler (in press).
Author/Editor Response
We thank Reindl and Berger for their generous support in establishing the method,1 and we agree that our study's failure to confirm their results is not due to technical differences. Serum antibodies against myelin oligodendrocyte glycoprotein and myelin basic protein had no prognostic value for progression to multiple sclerosis either in the total population or in subgroups analyzed in the Betaferon in Newly Emerging Multiple Sclerosis for Initial Treatment (BENEFIT) study, whereas other factors with known prognostic relevance, such as the number of hyperintense lesions on T2-weighted MRI scans or of gadolinium-enhancing lesions on T1-weighted MRI scans or the presence of oligoclonal bands in cerebrospinal fluid, were confirmed.2 A potential effect of genetic variability may be further elucidated in the ongoing analysis of DNA and RNA expression in the BENEFIT study. We doubt that the longer mean interval between blood sampling and the initial event had a major effect on the results, because we did not find any increased association by comparing patients who had shorter intervals with those who had longer intervals.
We remain convinced that our study provided an ideal basis for a definitive validation of claims such as those raised by Berger et al.3: it included a large number of patients from a representative sample of centers across Europe and Canada and was carefully monitored according to Good Clinical Practice standards.4 Patients were selected and observed according to predefined, independently evaluated and centrally reconfirmed inclusion and outcome criteria.
4 ReferencesLudwig Kappos, M.D.
Jens Kuhle, M.D.
University Hospital, CH-4031 Basel, Switzerland
lkappos@uhbs.ch Rupert Sandbrink, M.D., Ph.D.
Bayer Schering Pharma, 13342 Berlin, Germany1
Kuhle J ,Lindberg RL ,Regeniter A , et al. Antimyelin antibodies in clinically isolated syndromes correlate with inflammation in MRI and CSF. J Neurol 2007;254:160-168
CrossRef | Web of Science | Medline2
Kappos L ,Polman CH ,Freedman MS , et al. Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology 2006;67:1242-1249
CrossRef | Web of Science | Medline3
Berger T ,Rubner P ,Schautzer F , et al. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med 2003;349:139-145
Full Text | Web of Science | Medline4
Guideline for Good Clinical Practice: principles according to the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (topic E6). London: European Medicines Agency, 2002. (Accessed April 13, 2007, at http://www.emea.eu.int/pdfs/human/ich/013595en.pdf.)
