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[Multiple sclerosis: review of main experimental data and pathogenic hypotheses]
C Fressinaud1, L L Sarliève, G Vincendon
1Centre de Neurochimie du CNRS, Strasbourg.
Abstract:
The pathogenesis of multiple sclerosis (MS) is considered from three different viewpoints: genetic, viral and immunological. A genetic predisposition intervenes, as testified by the familial forms of MS and by the frequency of HLA A3B7 and DR2 groups in MS patients. The hypothesis of an inherited enzyme deficiency in oligodendrocytes is discussed. Many viruses are known to induce demyelination in animals, and the intrathecal production of antibodies to measles virus as well as the in vitro discovery of DNA transcripts of this virus in patients are suggestive of a viral factor. Experimental allergic encephalomyelitis (EAE) and chronic EAE have made it possible to study the immune and other mechanisms which might be involved in MS. While the myelin basic protein and the M2 antigen appear to be the first antigen targets, the demyelinating agents in this model are antibodies to galactocerebroside. The factors responsible for demyelination in MS have not yet been elucidated, but the antibodies present in the cerebrospinal fluid do not seem to be demyelinating in vitro. Descriptions of the cells which constitute the lesions and of the antigen markers they express suggest that endothelial cells and astrocytes (possibly presenting antigens to lymphocytes) might play a part in the genesis of the lesions. Experiments concerning the modulation and suppression of EAE allow new therapeutic approaches to be envisaged.
Insights
Multiple sclerosis (MS) pathogenesis involves genetic, viral, and immunological factors. Research explores potential inherited enzyme deficiencies, viral links like measles, and immune responses, including experimental allergic encephalomyelitis (EAE), to understand MS development and potential therapies.
Area of Science:
- Neuroimmunology
- Genetics
- Virology
Context:
- Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system.
- The exact cause of MS remains elusive, prompting investigation into multiple contributing factors.
- Familial forms and specific HLA types suggest a genetic predisposition.
Purpose:
- To review and synthesize current understanding of MS pathogenesis from genetic, viral, and immunological perspectives.
- To discuss the role of oligodendrocytes, viral infections (e.g., measles), and immune responses in MS.
- To explore insights gained from experimental allergic encephalomyelitis (EAE) models for understanding MS mechanisms and potential therapies.
Summary:
- Genetic factors, including familial clustering and HLA associations, play a role in MS susceptibility.
- Viral infections, particularly measles, are investigated as potential triggers, evidenced by intrathecal antibody production and viral DNA.
- Immunological mechanisms, studied via EAE models, highlight myelin basic protein, M2 antigen, and galactocerebroside antibodies as targets, though direct demyelinating activity of MS cerebrospinal fluid antibodies is unclear. Endothelial cells and astrocytes may also contribute to lesion formation.
Impact:
- Understanding the multifactorial pathogenesis of MS can guide the development of targeted therapies.
- Investigating viral and immunological triggers may lead to preventative strategies or novel treatment approaches.
- Insights from EAE models offer a framework for exploring immunomodulatory and immunosuppressive treatments for MS.