Relationship of immunologic abnormalities and disease stage in multiple sclerosis: implications for therapy

Multiple sclerosis is classified as an inflammatory cell-mediated autoimmune disease directed against central nervous system myelin. Different stages of disease appear to be related to different patterns of inflammation and changes on MRI. It is postulated that the lack of response to anti-inflammatory drugs in the secondary progressive stage relates to a neurodegenerative component that is immune independent. However, there is also evidence that the immune system itself is more abnormal in the secondary progressive phase according to a number of immune measures including dendritic cell function in the peripheral blood. Furthermore, neuropathologic studies suggest that there is inflammation in the brain of MS patients in the progressive stages in which inflammation takes a different form that includes a diffuse inflammatory process in the brain and activation of microglial cells. In summary, this implies that there may be different types of inflammation depending on the stage of MS with abnormalities in adaptive immunity playing an important role in the relapsing-remitting stage and innate immunity a more important role in the progressive stage.