Correspondence

Antimyelin Antibodies with No Progression to Multiple Sclerosis

N Engl J Med 2007; 356:426-428January 25, 2007

Article

To the Editor:

The presence of antibodies against myelin, myelin oligodendrocyte glycoprotein (MOG), and myelin basic protein (MBP) in serum from patients with a clinically isolated syndrome and multiple lesions detected on magnetic resonance imaging (MRI) has been associated with the more rapid development of a second neurologic event and conversion to clinically definite multiple sclerosis. However, there is controversy concerning this issue.1-3 Discordant results have not been explained, but clinical or laboratory differences in assay methods have been identified as possible causes. We investigated whether the presence of serum antibodies against MBP and MOG in patients with a clinically isolated syndrome was associated with the rate of and time to conversion to clinically definite multiple sclerosis. We used the same laboratory methods as the investigators who reported such an association.1

Our study was based on longitudinal clinical, cerebrospinal fluid, and MRI data prospectively collected from a cohort of patients with a clinically isolated syndrome; recruitment started in 1995.4,5 Brain MRI was performed within 3 months after the first demyelinating event. From the total cohort of 463 patients, only the 290 patients with frozen serum samples were considered for inclusion in these analyses. There were no significant differences in demographic, clinical, or MRI characteristics between the group with preserved serum samples and the group without preserved samples. A total of 114 patients with a clinically isolated syndrome were included in the analysis. We used the same inclusion criteria that were used previously1: abnormal baseline MRI as described by Fazekas et al., at least 1 year of follow-up, and a positive test for oligoclonal bands. Serum samples were evaluated by technicians who were not aware of the clinical status of the patients. Antibody tests were determined according to a previously described technique.3,6,7 We compared the characteristics of the patients and their disease according to antibody status by means of one-way analysis of variance, chi-square testing, or Kruskal–Wallis testing. A P value of 0.05 or lower was considered to indicate statistical significance.

After a mean (±SD) follow-up period of 46.7±21.2 months, there were no significant differences in the rate of conversion to clinically definite multiple sclerosis according to antibody status. Moreover, among patients with conversion to clinically definite multiple sclerosis during the study period, no significant differences in the median time to conversion were found between patients with and those without antimyelin antibodies (Table 1Table 1Conversion to Clinically Definite Multiple Sclerosis among 114 Patients with a Clinically Isolated Syndrome, According to Antibody Status.).

Our study, which used the same assay as that used in the previously reported study,1 did not show an association between the presence of antimyelin antibodies and a higher or earlier rate of conversion to clinically definite multiple sclerosis.

Raul Pelayo, M.D.
Mar Tintoré, M.D.
Xavier Montalban, M.D.
Alex Rovira, M.D.
Carmen Espejo, Ph.D.
Vall d'Hebron University Hospital, 08035 Barcelona, Spain

Markus Reindl, Ph.D.
Thomas Berger, M.D.
Innsbruck Medical University, A-6020 Innsbruck, Austria

7 References

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Citing Articles (8)

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   Ulf Ziemann, Mathias Wahl, Elke Hattingen, Hayrettin Tumani. (2011) Development of biomarkers for multiple sclerosis as a neurodegenerative disorder. Progress in Neurobiology 95:4, 670-685
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   Jens Kuhle, Axel Petzold. (2011) What makes a prognostic biomarker in CNS diseases: strategies for targeted biomarker discovery? Part 2: chronic progressive and relapsing disease. Expert Opinion on Medical Diagnostics 5:5, 393-410
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   M. Comabella, M. Fernandez, R. Martin, S. Rivera-Vallve, E. Borras, C. Chiva, E. Julia, A. Rovira, E. Canto, J. C. Alvarez-Cermeno, L. M. Villar, M. Tintore, X. Montalban. (2010) Cerebrospinal fluid chitinase 3-like 1 levels are associated with conversion to multiple sclerosis. Brain 133:4, 1082-1093
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   Johannes Brettschneider, Troy D. Jaskowski, Hayrettin Tumani, Sana Abdul, Dee Husebye, Haniah Seraj, Harry R. Hill, Ella Fire, Larissa Spector, Jennifer Yarden, Nir Dotan, John W. Rose. (2009) Serum anti-GAGA4 IgM antibodies differentiate relapsing remitting and secondary progressive multiple sclerosis from primary progressive multiple sclerosis and other neurological diseases. Journal of Neuroimmunology 217:1-2, 95-101
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   Keren Politi Elishkevitz, Udi Nussinovitch, Moshe Nussinovitch. (2009) Lactic Dehydrogenase Isoenzymes in Adolescents With Multiple Sclerosis. Pediatric Neurology 41:4, 259-262
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   Bettina Kuenz, Florian Deisenhammer, Thomas Berger, Markus Reindl. (2007) Diagnostic biomarkers in multiple sclerosis. Expert Opinion on Medical Diagnostics 1:2, 225-233
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7. 7

   (2007) Lack of Association between Antimyelin Antibodies and Progression to Multiple Sclerosis. New England Journal of Medicine 356:18, 1888-1889
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   Kuhle, Jens, Pohl, Christoph, Mehling, Matthias, Edan, Gilles, Freedman, Mark S., Hartung, Hans-Peter, Polman, Chris H., Miller, David H., Montalban, Xavier, Barkhof, Frederik, Bauer, Lars, Dahms, Susanne, Lindberg, Raija, Kappos, Ludwig, Sandbrink, Rupert, . (2007) Lack of Association between Antimyelin Antibodies and Progression to Multiple Sclerosis. New England Journal of Medicine 356:4, 371-378
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