Polymorphisms of HLA class II genes in Japanese patients with pemphigus vulgaris

Abstract

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.

HLA Class II Polymorphism Contributes to Specify Desmoglein Derived Peptides in Pemphigus Vulgaris and Pemphigus Foliaceus

“…Our results confirm previous reports showing a strong association of PV with DQB1*0503 which is in linkage disequilibrium with DR14 alleles [3,4,5,8,10,12,13,14,15,16,17]. Since the DQB1*0503 PV patients had various DRB1*14 related alleles, one alternative The AA residues are shown using the letter code.…”

“…In PV Japanese patients, additional DRB1* PV-related alleles were observed: DRB1*0406, 1405 and 1406 [15,16,17]. We have shown that the pockets of the DRB1*1401, 05, 06 and 0406 molecules have great similarities (Table 2A) suggesting that all these PV-associated DR molecules may present the same self-peptide(s).…”

“…The P4 and P7 pockets of DRB1*0406 are positively charged (arginine at position 71) and are therefore unlikely to bind a positively charged peptide such as DRB1*0402 molecule. In PV Japanese patients, additional DRB1*14 alleles were observed: DRB1*1405, 1406 [15,16,17]. The DRB1*1401, 05, 06 and 0406 alleles share the same P1 and P7 pockets and also a functionally identical P4 pocket (Table 2A).…”

“…The DRB1*1401 or 1404 alleles were found associated with PV in non-Jewish patients of European ancestry (Italy, Sardinia, Spain, Boston area) [3,4,5,6] and in Asian populations (India, Pakistan, Japan) [12,13,14,15,16,17].…”

Disease Relevant HLA Class II Alleles Isolated by Genotypic, Haplotypic, and Sequence Analysis in North American Caucasians with Pemphigus Vulgaris

“…However, population studies of patients with PV have clearly shown that there are differences among the most prevalent alleles in various ethnic groups (summarized in Table 1). Nine DRB1 alleles have been associated with PV (DRB1*0402, *0403, *0406, *0802, *0804, *1401, *1404, *1405, *1408) in 11 distinct populations [12][13][14][15][16][17][18][19][20]. Two DQB1 alleles, DQB1*0302 and DQB1*0503, are associated with PV patients across the world as well [9,12,13,15,19,21].…”