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

Tissue Antigens. 2000 Feb;55(2):140-8. doi: 10.1034/j.1399-0039.2000.550205.x.


Multiple sclerosis (MS) is a presumed autoimmune disease of the central nervous system, shown to be associated with the HLA class II haplotype DRB1*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 typing technique for HLA class I and class II genes, 200 Swedish MS patients and 210 Swedish healthy controls were analysed for their HLA alleles. Additional HLA class I alleles that increase and decrease the genetic susceptibility 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 first to identify a major modulating effect of HLA class I alleles on the susceptibility to a human autoimmune disease; a phenomenon that has previously only been observed in animal models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Autoimmune Diseases
  • HLA-A Antigens / genetics*
  • HLA-B Antigens / genetics*
  • HLA-DQ Antigens / genetics*
  • HLA-DQ beta-Chains
  • HLA-DR Antigens / genetics*
  • HLA-DRB1 Chains
  • Humans
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology
  • Risk Factors


  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • HLA-DR Antigens
  • HLA-DRB1 Chains