Multiple sclerosis: a modifying influence of HLA class I genes in an HLA class II associated autoimmune disease

Multiple sclerosis (MS) is a presumed autoimmune disease of the central ner vous system, shown to be associated with the HLA class II haplotype DRBI*15 ,DQB1*06. Carrying the HLA class II haplotype DRB1*15,DQB1*06 increases the risk of MS by 3.6, By adopting a polymerase chain reaction (PCR)-based typ ing technique for HLA class I and class II genes, 200 Swedish MS patients a nd 210 Swedish healthy controls were analysed for their HLA alleles. Additi onal HLA class I alleles that increase and decrease the genetic susceptibil ity to MS were identified. The HLA-A*0301 allele increases the risk of MS ( odds ratio-2.1) independently of DRB1*15,DQB1*06. HLA-A*0201 decreases the overall risk (odds ratio= 0.52) and the presence of A*0201 reduces the risk of MS for DRB1*15,DQB1*06 carriers from 3.6 to 1.5. Our findings are the f it st to identify a major modulating effect of HLA class I alleles on the s usceptibility to a human autoimmune disease: a phenomenon that has previous ly only been observed in animal models.