Immunological mechanisms in multiple sclerosis

Abstract

Multiple sclerosis (MS) remains a leading cause of neurologic disability among young adults. Clinical manifestations of the disease result from immune-mediated demyelination of the central nervous system. Most patients experience new symptoms in a relapsing-remitting pattern, although the course is highly variable from person to person and even in the same individual over time.

Recent neuropathological studies reveal that in addition to the surrounding myelin sheath, nerve axons themselves are targets of injury in MS lesions. Characterization of the inflammatory infiltrates present in MS brain and spinal cord tissue shows that active lesions can be segregated into 1 of 4 subtypes, with each individual having only a single pattern of involvement. Studies in animal models demonstrate that a number of myelin proteins can become immune system targets resulting in demyelination, and these models have also served to define multiple immunological mechanisms of disease. Translational studies using peripheral blood samples have characterized differences in the various myelin protein-reactive immune responses of MS patients and controls, and these investigations have validated some, but not all, of the disease mechanisms uncovered in animals. Adaptive and innate immunity both appear to contribute to disease pathogenesis within the target tissue of the central nervous system.

Immunomodulatory therapies have been developed that partially arrest disease relapses and progression. Studies to dissect how these agents work have shed light on underlying disease mechanisms in MS. More effective interventions in the future will need to target multiple points in disease pathways.