ABSTRACT

Multiple sclerosis (MS) has long been accepted as an inflammatory disease limited to the central nervous system (CNS). The etiology of the disease, particularly the initial inciting event, remains unknown. The purpose of this chapter is to outline the evidence supporting an autoimmune etiology for MS. In presenting this evidence, it is helpful to review the revised postulates of Witebsky, published by Rose and Bona in 1993, which establish the criteria for denoting a disease as autoimmune in origin (1). The original postulates required that an autoimmune response be recognized in the form of an autoantibody or cell-mediated immunity; the corresponding autoantigen be identified; an analogous autoimmune response be induced in an experimental animal, and the immunized animal then develop a similar disease. The revised postulates sought to distinguish pathogenic from nonpathogenic Band T-cell responses and to characterize the evidence for these responses into direct proof, indirect evidence, and circumstantial evidence.