It has previously been demonstrated that susceptibility to pemphigus vulgaris is associated with human leukocyte antigen (HLA)-DR4 serologic specificity among Ashkenase Jews, and with DR4 as well as DR6 (DR14) in other ethnic groups. We genotyped HLA-DRB1, DQA1, DQB1, and DPB1 alleles in 16 patients with pemphigus by polymerase chain reaction-restriction fragment length polymorphism, to find evidence of potential HLA class II allele associations with pemphigus in Japanese patients who have a relatively homogeneous ethnic background. All nine patients with pemphigus vulgaris and five of seven patients with pemphigus foliaceus carried one or two alleles of HLA-DRB1*04 (*0403, *0406) and HLA-DRB1*14 (*1401, *1405, *1406) subtypes. Sequence analysis of these DRB1*04 and DRB1*14 alleles revealed the amino acid homology of phenylalanine at position 26 and valine at position 86 with the DRB1*0402 allele that reportedly confers a strong susceptibility to pemphigus vulgaris in Ashkenazi Jews. Thus our findings, together with previous HLA studies on pemphigus vulgaris patients of different ethnic groups, suggest that HLA-DRB1*04 and DRB1*14 alleles are commonly associated with pemphigus vulgaris across racial barriers. These HLA-DRB1 alleles are likely to be also associated with pemphigus foliaceus. Further studies on more diverse ethnic populations will be helpful in determining the significance of the association between certain amino acid residues of the class II molecules and disease susceptibility to pemphigus vulgaris as well as pemphigus foliaceus.

Pemphigus vulgaris (PV) is an autoimmune disease mediated by autoantibodies that bind to a keratinocyte adhesion molecule, desmoglein-3. The purpose of this study was to identify critical amino acid residues of PV-associated HLA class II genes. Haplotype and allele distributions, along with molecular polymorphisms, of HLA class II genes were analyzed based on the polymerase chain reaction-restriction fragment length polymorphism in 17 Japanese PV patients. Each patient had one or two alleles of DRB1*04 (*0403, *0404, *0406) or DRB1*14 (*1401, *1405, *1406) subtypes. All DRB1*04 and DRB1*14 alleles carried by PV patients with different ethnic backgrounds reported to date, including DRB1*0402, which confers strong susceptibility to PV among Jewish populations, have amino acid residues Phe26, Leu67 or Ile67, and Val86, as well as hydrophilic amino acid residues at positions 70 and 71 of the DRB1 beta chain.

No abstract