Correspondence
Antimyelin Antibodies in Multiple Sclerosis
N Engl J Med 2003; 349:2269-2271December 4, 2003
- Article
To the Editor:
In their article on the use of antimyelin antibodies in multiple sclerosis (July 10 issue),1 Berger and colleagues restrict their report to IgM antibodies alone. Autoantibodies of the IgG class are, in general, more specific markers of autoimmune disease than those of the IgM class. Were IgG antibodies measured, and if so, how did they perform?
The authors also report that of the nine patients who were originally seronegative for antibodies and who subsequently had a relapse, eight were seropositive for antibodies at the time of relapse. Were antibodies measured sequentially in all the patients? If they were, what was the interval between the appearance of antibodies and the relapse, and did antibodies develop in other seronegative patients during the course of the study? This information is needed to assess the potential of the use of the test for the prediction of relapse.
1 ReferencesGerald A. Maguire, Ph.D.
Addenbrooke's Hospital, Cambridge CB2 2QR, United Kingdom
gam1004@cam.ac. uk 1
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 | Medline
To the Editor:
Berger and colleagues show that the presence of serum antibodies to myelin oligodendrocyte glycoprotein (MOG) and to myelin basic protein (MBP) in patients with suspected multiple sclerosis predicts early conversion to clinically definite disease. By Western blot analysis they detected anti-MOG IgM antibodies in 64 of 103 patients. Their report raises issues concerning the pathogenesis of multiple sclerosis. In particular, it would be of interest to know whether anti-MOG IgM antibodies seroconvert to IgG antibodies when multiple sclerosis becomes definite, since the diagnosis of multiple sclerosis rests on IgG oligoclonality. There is also the problem of discrepancies between Western blotting and enzyme-linked immunosorbent assay in the detection of anti-MOG IgG antibodies.1-3 Anti-MOG antibodies can occur in various neurologic diseases, including non–immune-mediated conditions, so their presence, even in association with neurologic signs or findings on magnetic resonance imaging, does not point unequivocally to multiple sclerosis. I therefore propose that involved centers should coordinate efforts to validate clinically the use of antimyelin antibodies in multiple sclerosis.
3 ReferencesRenato Mantegazza, M.D.
National Neurologic Institute Carlo Besta, 20133 Milan, Italy
rmantegazza@istituto-besta.it 1
Reindl M ,Linington C ,Brehm U , et al. Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study. Brain 1999;122:2047-2056
CrossRef | Web of Science | Medline2
Lindert R-B ,Haase CG ,Brehm U ,Linington C ,Wekerle H ,Hohlfeld R . Multiple sclerosis: B- and T-cell responses to the extracellular domain of the myelin oligodendrocyte glycoprotein. Brain 1999;122:2089-2100
CrossRef | Web of Science | Medline3
Kennel De March A ,De Bouwerie M ,Kolopp-Sarda MN ,Faure GC ,Bene MC ,Bernard CC . Anti-myelin oligodendrocyte glycoprotein B-cell responses in multiple sclerosis. J Neuroimmunol 2003;135:117-125
CrossRef | Web of Science | Medline
To the Editor:
Although Antel and Bar-Or imply in their Perspective article1 that antimyelin antibodies contribute to disease progression in multiple sclerosis, it is difficult to accept this hypothesis, for several reasons. First, these antibodies are present in neurologic diseases such as head injury, stroke, amyotrophic lateral sclerosis, and encephalitis2-4; second, IgM or IgG antimyelin antibodies would poorly penetrate an intact blood–brain barrier; third, plasma exchange or intravenous immunoglobulin does not modify the progression of multiple sclerosis5; and fourth, there is no pathological evidence that antimyelin-antibody–dependent neuronal injury occurs in multiple sclerosis.5
Antimyelin antibodies are epiphenomena in multiple sclerosis. We would be concerned if the results of this study were used to persuade patients who are positive for antibodies and have clinically isolated demyelinating syndromes to receive immunotherapy for multiple sclerosis.
5 ReferencesAbhijit Chaudhuri, D.M., M.D.
Peter O. Behan, D.Sc., M.D.
University of Glasgow, Glasgow G51 4TF, United Kingdom
ac54p@udcf.gla. ac. uk 1
Antel JP ,Bar-Or A . Do myelin-directed antibodies predict multiple sclerosis? N Engl J Med 2003;349:107-109
Full Text | Web of Science | Medline2
Mukherjee A ,Vogt RF ,Linthicum DS . Measurement of myelin basic protein by radioimmunoassay in closed head trauma, multiple sclerosis and other neurological diseases. Clin Biochem 1985;18:304-307
CrossRef | Web of Science | Medline3
Ruutiainen J ,Arnadottir T ,Molnar G ,Salmi A ,Frey H . Myelin basic protein antibodies in the serum and CSF of multiple sclerosis and subacute sclerosing panencephalitis patients. Acta Neurol Scand 1981;64:196-206
CrossRef | Web of Science | Medline4
Lisak RP ,Zwiman B ,Norman M . Antimyelin antibodies in neurological diseases: immunofluorescent demonstration. Arch Neurol 1975;32:163-167
Web of Science | Medline5
Behan PO ,Chaudhuri A ,Roep BO . The pathogenesis of multiple sclerosis revisited. J R Coll Physicians Edinb 2002;32:244-265
Author/Editor Response
Drs. Chaudhuri and Behan are concerned about the hypothesis that antimyelin antibodies may contribute to disease progression in multiple sclerosis. However, recent work has shown that T-cell–dependent inflammation, which is responsible for a local breakdown of the blood–brain barrier and subsequent influx of cellular and humoral immune components, is not sufficient to cause the typical demyelinating plaques of multiple sclerosis. Antibodies have been identified as one potential cause of demyelination in multiple sclerosis.1,2 Furthermore, plasmapheresis is effective in certain patients with multiple sclerosis.3 Although antimyelin antibodies are present in other neurologic diseases,4 we would like to emphasize again that our study was powered to determine the prognostic, rather than diagnostic or therapeutic, value of antimyelin antibodies. Because one disease-modifying substance is widely approved for use in patients with a clinically isolated syndrome,5 we do not share the concern that patients will be persuaded to start this treatment on the basis of our study results.
Further relapses were not assessed in our study because the primary end point was the time to a first relapse in patients with a clinically isolated demyelinating event. We agree with Dr. Maguire that the prognostic value of antimyelin antibodies requires investigations in patients with established relapsing and remitting multiple sclerosis in order to determine whether antimyelin antibodies may also predict further relapses. However, such a study would be complex, especially because of variable durations of disease and variable therapeutic effects. In cooperation with other multiple sclerosis centers, we are currently performing a longitudinal study to investigate this important issue. We have previously shown that anti-MOG IgG antibodies are detected more often in patients with relapsing and remitting and secondary chronic progressive disease than in those with clinically isolated syndromes.5 Therefore, topics addressed in the ongoing study also include the dynamics of antimyelin immunoglobulin subclass switching and the potential influence of different therapies on antimyelin antibodies.
5 ReferencesThomas Berger, M.D.
Markus Reindl, Ph.D.
University of Innsbruck, A-6020 Innsbruck, Austria
thomas.berger@uibk. ac. at 1
Lassmann H ,Bruck W ,Lucchinetti C . Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy. Trends Mol Med 2001;7:115-121
CrossRef | Web of Science | Medline2
Kornek B ,Lassmann H . Neuropathology of multiple sclerosis -- new concepts. Brain Res Bull 2003;61:321-326
CrossRef | Web of Science | Medline3
Weinshenker BG ,O'Brien PC ,Petterson TM , et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol 1999;46:878-886
CrossRef | Web of Science | Medline4
Reindl M ,Linington C ,Brehm U , et al. Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study. Brain 1999;122:2047-2056
CrossRef | Web of Science | Medline5
Jacobs LD ,Beck RW ,Simon JH , et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. N Engl J Med 2000;343:898-904
Full Text | Web of Science | Medline
- Citing Articles (2)
Citing Articles
1
Doris Lambracht-Washington, Kevin C. O'Connor, Elizabeth M. Cameron, Andrea Jowdry, E. Sally Ward, Elliot Frohman, Michael K. Racke, Nancy L. Monson. (2007) Antigen specificity of clonally expanded and receptor edited cerebrospinal fluid B cells from patients with relapsing remitting MS. Journal of Neuroimmunology 186:1-2, 164-176
CrossRef2
Richard Foa. (2004) BACK FROM CAPE COD. Neurology Today 4:7, 4
CrossRef
