Polymorphisms of HLA‐DR and ‐DQ Genes in Japanese Patients with Bullous Pemphigoid

Abstract

Bullous pemphigoid (BP), an autoimmune skin disease of the elderly, is mediated by autoantibodies that bind to hemidesmosomes of epidermal basal cells. This study investigated BP-associated HLA-DR and -DQ genes among Japanese patients. We analyzed HLA-DR and -DQ genes among 23 Japanese BP patients based on the polymerase chain reaction-restriction fragment length polymorphism. Eighteen of these 23 patients (78%) carried at least one allele of HLA-DRB1*04 or DRB1*1101, with significant increases in HLA-DRB1*04 (*0403, *0406)/DQA1*0301/DQB1*0302 and DRB1*1101/DQA1*0505/DQB1*0302 haplotypes as well as the individual alleles DRB1*1101 and DQB1*0302 (corrected p < 0.05 for each comparison), when compared to control subjects. These data differ from the accepted DQB1*0301 (DQ7) association with the same disease among Caucasians. These findings indicate that different HLA class II haplotypes genetically influence susceptibility to BP among different ethnic groups. Our findings, together with previous reports on Caucasian patients with the pemphigoid group of bullous diseases, suggest that HLA-DRB1 molecules might participate in the regulation of autoimmune responses to BP antigens.

Bullous Pemphigoid Associated with Silicosis

“…The pathomechanism in the production of the autoantibodies remains to be clarified, although several drug-induced cases suggested the involvement of immune dysregulation by such drugs [10, 11, 12]. Okazaki et al [13]studied the HLA genotypes in Japanese BP patients and found a higher incidence of DRB1 *0403, *0406, DQB1 *0302 haplotype, as well as the individual alleles DRB1 *1101 and DQB1 *0302. Our present patient showed different HLA genotypes.…”

Identification of Quantitative Trait Loci in Experimental Epidermolysis Bullosa Acquisita

“…In more detail, pemphigus vulgaris, an ASBD with Dsg 3 as the target antigen (Amagai et al, 1991), was found to be associated with HLA-DRW4 in a Jewish cohort, with HLA-DQw1 and -DQw3 polymorphisms in Ashkenazi Jews, HLA-DRB1*04 and DRB1*1401 in Iranian patients, HLA-DRB1*0402 haplotypes in Venezuelan patients, HLA-DQB1*0503, -B*1507 or -DRB1*1405 in Japanese patients, as well as HLA-B38 and HLA-Bw55 in an American cohort (Park et al, 1979;Szafer et al, 1987;Miyagawa et al, 1999Miyagawa et al, , 2002Lee et al, 2006;Saenz-Cantele et al, 2007;Shams et al, 2009). For bullous pemphigoid (BP), an ASBD with antibodies directed against hemidesmosomal proteins termed BP180 (type XVII collagen, COL17) and BP230 (Stanley et al, 1981(Stanley et al, , 1988Diaz et al, 1990), major histocompatibility complex (MHC) association studies have also not been conclusive (Delgado et al, 1996;Okazaki et al, 2000). In 29 patients with epidermolysis bullosa acquisita (EBA) and 5 patients with bullous lupus erythematodes, an association with HLA-DR2 has been described (Gammon et al, 1988).…”

Estudo da associação entre antígenos de histocompatibilidade leucocitária e penfigoide bolhoso em pacientes brasileiros

“…Em um outro estudo simultâneo com a população japonesa foram analisados os genes HLA-DR e -DQ em 23 casos com PB, e os pesquisadores obtiveram um aumento significativo de HLA-DRB1*04 (*0403, *0406)/DQA1*0301/DQB1*0302 e DRB1*1101/DQA1*0505/DQB1*0302 haplótipos, bem como os alelos individuais DRB1*1101 e DQB1*0302 (corrigido p < 0,05 para cada comparação), quando conferidos com os controles [75] .…”

“…Apesar de estudos anteriores [74,75] não comprovarem a associação com alelos classe I em outras populações, na brasileira foi possível evidenciar essa característica. Portanto, é a primeira vez que se demonstrou a correlação de um HLA classe I com o penfigoide bolhoso.…”

“…O HLA classe I foi identificado em diversos estudos em associações de casos e controles, tais como em lúpus eritematoso sistêmico [96] , psoríase [97] e vitiligo [98] ; [75] , não houve diferença estatisticamente significante.…”