In this study, researchers in the lab of Paul Terasaki at the University of California, Los Angeles, identified the primary genetic association for multiple sclerosis. In 1970, Terasaki organized a workshop that identified 11 official HL-A specificities (HL-A1, 2, 3, 5, 7, 8, 9, 10, 11, 12 and 13), and perhaps eight other specificities. In this study, his group concluded, from 94 patients and 871 controls, that HL-A3 was overrepresented in patients with multiple sclerosis. Furthermore, the team demonstrated that the geographical variation in prevalence of multiple sclerosis paralleled the prevalence of HL-A3. They summarised some of the epidemiology that suggested an environmental cause for multiple sclerosis and concluded that “the evidence to date on MS, however, is still consistent with the idea that a genetic difference in susceptibility underlies some environmental influence.” Terasaki and others later discovered the association with what would come to be called the class II allele HLA-DR15, which is within the HL-A3 region and which remains the best characterized candidate susceptibility gene for multiple sclerosis. Only in the last few years has sufficient power emerged in the techniques and cohorts, forged through large collaborations (especially the International MS Genetics Consortium), to uncover the much smaller individual genetic contributions of a host of other alleles. The finding that multiple sclerosis is associated with the HLA system implicates the immune system in its pathogenesis; explains some of the geographical variation of the disease; provides a molecular substrate for the interaction of genetics and environment; and suggests treatment directed at the T-lymphocyte, the T cell receptor, and the class II molecule.
Suggested By Alastair Compston and alasdair coles
In this study, researchers in the lab of Paul Terasaki at the University of California, Los Angeles, identified the primary genetic association for multiple sclerosis. In 1970, Terasaki organized a workshop that identified 11 official HL-A specificities (HL-A1, 2, 3, 5, 7, 8, 9, 10, 11, 12 and 13), and perhaps eight other specificities. In this study, his group concluded, from 94 patients and 871 controls, that HL-A3 was overrepresented in patients with multiple sclerosis. Furthermore, the team demonstrated that the geographical variation in prevalence of multiple sclerosis paralleled the prevalence of HL-A3. They summarised some of the epidemiology that suggested an environmental cause for multiple sclerosis and concluded that “the evidence to date on MS, however, is still consistent with the idea that a genetic difference in susceptibility underlies some environmental influence.” Terasaki and others later discovered the association with what would come to be called the class II allele HLA-DR15, which is within the HL-A3 region and which remains the best characterized candidate susceptibility gene for multiple sclerosis. Only in the last few years has sufficient power emerged in the techniques and cohorts, forged through large collaborations (especially the International MS Genetics Consortium), to uncover the much smaller individual genetic contributions of a host of other alleles. The finding that multiple sclerosis is associated with the HLA system implicates the immune system in its pathogenesis; explains some of the geographical variation of the disease; provides a molecular substrate for the interaction of genetics and environment; and suggests treatment directed at the T-lymphocyte, the T cell receptor, and the class II molecule.