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Keywords:

  • A*0201;
  • A*0301;
  • allele-specific amplification;
  • autoimmunity;
  • histocompatibility testing;
  • genetic susceptibility;
  • HLA class I association;
  • multiple sclerosis;
  • DPB1*0401;
  • polymerase chain reaction

Acknowledgments:

This study was supported by grants from the Swedish Medical Research Council, the Childrens’ Cancer Foundation, the Tobias Foundation and the Swedish association of the Neurologically Disabled.

Abstract:

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.