HLA Class II Susceptibility to Multiple Sclerosis Among Ashkenazi and Non-Ashkenazi Jews

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Abstract
IT IS well documented that genetic factors are involved in the pathogenesis of multiple sclerosis (MS).1-3 As with many autoimmune diseases, the genetic susceptibility to MS is determined by genes encoded within the HLA class II region. In most population studies, the DR2-related haplotype, molecularly termed DRB1*1501, DQA1*0102, DQB1*0602, was reported to increase susceptibility to MS.4-9 This association, however, is not homogeneously distributed worldwide, as shown by the collaborative French Canadian-Sardinian study, in which a different association of MS with DR4, DQA1*0301, DQB1*0201, and DQB1*0302 alleles was found among Sardinians.10,11 Recently, complete genomic screening of affected members of families with MS indicated a linkage to the HLA region.12,13 It has also been suggested that specific amino acids in the peptide-binding groove of the HLA class II DRB1,14 DQA1,15,16 and DQB115,17 molecules are important in determining susceptibility to MS.