Multiple Sclerosis,

Antimyelin Antibodies and Mimicry in a new BM&L debate this week

 

In the July 10 Number of the New England Journal of Medicine, three extremely intriguing articles on Multiple Sclerosis (MS) rise a very interesting debate, which BRAIN MIND & LIFE INTERNATIONAL will dedicate the next week-end workshop session.

For participation information, please write to info@brainmindlife.org, subject: INTERNATIONAL: Antimyelin Antibodies in MS.

An article by Jack P. Antel, M.D., and Amit Bar-Or, M.D. (Do Myelin-Directed Antibodies Predict Multiple Sclerosis? Vol 349: 107-109, Number 2, July 10, 2003) introduces the problem of the early axonal injury depending on the primary lesion directed at the myelin itself or its cell of origin, the oligodendrocyte, and discusses the role of myelin-directed antibodies in predicting the developing of MS. The research article by Thomas Berger, M.D., Paul Rubner, M.D., Franz Schautzer, M.D., Robert Egg, M.D., Hanno Ulmer, Ph.D., Irmgard Mayringer, M.D., Erika Dilitz, M.D., Florian Deisenhammer, M.D., and Markus Reindl, Ph.D. (Antimyelin Antibodies as a Predictor of Clinically Definite Multiple Sclerosis after a First Demyelinating Event. Vol 349: 139-145, Number 2, July 10, 2003) suggests a new diagnostic tool for MS. Here we report the entire abstract:

 Background Most patients with multiple sclerosis initially present with a clinically isolated syndrome. Despite the fact that clinically definite multiple sclerosis will develop in up to 80 percent of these patients, the course of the disease is unpredictable at its onset and requires long-term observation or repeated magnetic resonance imaging (MRI). We investigated whether the presence of serum antibodies against myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP) in patients with a clinically isolated syndrome predicts the interval to conversion to clinically definite multiple sclerosis.

Methods A total of 103 patients with a clinically isolated syndrome, positive findings on cerebral MRI, and oligoclonal bands in the cerebrospinal fluid were studied. At base line, serum samples were collected to test for anti-MOG and anti-MBP antibodies with Western blot analysis, and the lesions detected by cerebral MRI were quantified. Neurologic examinations for relapse or disease progression (defined as conversion to clinically definite multiple sclerosis) were performed at base line and subsequently every three months.

Results Patients with anti-MOG and anti-MBP antibodies had relapses more often and earlier than patients without these antibodies. Only 9 of 39 antibody-seronegative patients (23 percent) had a relapse, and the mean (±SD) time to relapse was 45.1±13.7 months. In contrast, 21 of 22 patients (95 percent) with antibodies against both MOG and MBP had a relapse within a mean of 7.5±4.4 months, and 35 of 42 patients (83 percent) with only anti-MOG antibodies had a relapse within 14.6±9.6 months (P<0.001 for both comparisons with antibody-seronegative patients). The adjusted hazard ratio for the development of clinically definite multiple sclerosis was 76.5 (95 percent confidence interval, 20.6 to 284.6) among the patients who were seropositive for both antibodies and 31.6 (95 percent confidence interval, 9.5 to 104.5) among the patients who were seropositive only for anti-MOG antibodies, as compared wit seronegative patients.

Conclusions 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. This finding may be important for the counseling and care of patients with a first demyelinating event suggestive of multiple sclerosis.

 

The third article is written by Hartmut Wekerle, M.D., and Reinhard Hohlfeld, M.D. (Molecular Mimicry in Multiple Sclerosis. Vol 349: 185-186, Number 2, July 10, 2003). A recent research by Lang and his colleagues, centred on molecular mimicry, newly attracted the attention on this mechanism for the pathogenesis of MS. In fact, most researchers believe that multiple sclerosis is an autoimmune disease in which T cells recognize and attack components of the axonal myelin sheath and other features of the central nervous system, destroying myelin and the underlying axon. Although self-reactive T cells are present in the immune system of people with multiple sclerosis, they are also found in a quiescent state in perfectly healthy people. Their pathogenic potential is realized only on acute activation, which can occur through different mechanisms. Molecular mimicry is believed one of the presumed triggers of autoimmunity.

BM&-July2003