Immune aspects of multiple sclerosis

Multiple sclerosis (MS) is an inflammatory demyelinating disease affecting the central nervous system (CNS) in a manner suggestive of an immunologically mediated mechanism, with a genetical complex susceptibility (reviewed by Stoch and Lassmann, 1997). In the regions of the world that are concerned, it represents the major cause of CNS disease in young adults. The heterogeneity of MS pathology has been particularly well documented by H. Lassmann his collaborators (Lucchinetti et al., 1996). They described at least five types of demyelination process, based mainly on the preservation or loss of oligodendrocytes. At the same time, they staged the demyelinating activity in MS plaques on the basis of the presence of myelin degradation products and macrophage activation markers. Importantly, they found that in a given patient, the type of demyelination process did not correlate with the stage of demyelinating activity of the different plaques. Rather, the mechanism was characteristis of all lesions found in each patient. This suggests that different pathogenic pathways may lead to demyelination in different patients. For example, in some cases the process seems to be directed primarily at the myelin sheath, with relative sparing of oligodendrocytes. This suggests immune mediated demyelination analogous to that of some of the forms of experimental autoimmune encephalomyelitis (EAE), or to the demyelination seen in the Theiler’s virus model. In other cases there is primary oligodendrocyte destruction which could indicate direct viral infection of this cell population. As recently discussed, a viral origin has for long been suggested but none of the viral candidates has stood the test of time (Monteyne et al., 1998a). Substantial damage to axons has also been noted in the CNS of some MS patients. Axonal transection could be one cause of the irreversible neurologic impairments of MS (Trapp et al., 1998).Thèse d'agrégation de l'enseignement supérieur (MEXP) -- UCL, 199