8 - Immunogenetics of multiple sclerosis

Abstract

This chapter discusses the genetic aspects of multiple sclerosis. Multiple sclerosis is an inflammatory demyelinating disease of unknown cause. Current opinion holds that multiple sclerosis will likely prove to be an autoimmune process, an infectious disease, or some combination of the two. Several lines of evidence buttress this opinion, but all the evidence is indirect. Certain facts have been established in multiple sclerosis that are consistent with an autoimmune or infectious basis for the disease, and these facts ultimately will have to be incorporated into any coherent theory of its pathogenesis. The chapter presents data obtained in family studies that indicate that concordance for multiple sclerosis in monozygotic twins exceeds that in dizygotic twins. On the basis of the analysis of the family studies of multiple sclerosis conducted to date, researchers are able to draw only a few conclusions based on these data alone. Concordance for multiple sclerosis in monozygotic twins does not exceed 25% and is probably lower. This finding proves that genetic endowment alone does not suffice for multiple sclerosis. Moreover, studies of HLA in multiple sclerosis siblings concordant for multiple sclerosis reveals more shared haplotypes than chance would predict. This finding argues yet again that HLA endowment is a major determinant of susceptibility to multiple sclerosis.