Pemphigus vulgaris (PV) is a blistering disease of the skin and mucous membranes characterized by an autoantibody response against a keratinocyte adhesion molecule, desmoglein 3, causing acantholysis and blister formation. We compared high resolution MHC class II alleles and haplotype frequencies (HLA-DRB, DQA1 and DQB1) in 37 patients with PV to 89 haplotypes of normal relatives from New Delhi and Ahmedabad. We found that PV patients had significantly increased frequencies of DRB1*1404 (P < 0.0001), DQA1*0101 (P = 0.001), and DQB1*0503 (P < 0.0001). These associations were due to the increased frequencies of the haplotype HLA-DRB1*1404, DRB3*0202, DQA1*0101, DQB1*0503 in patients compared to control haplotypes (p < 0.0001). Also, patients from Ahmedabad had a significant increase in HLA-DQB1*0302 (p = 0.03). An identical amino acid sequence (Leu-Leu-Glu-Arg-Arg-Arg-Ala-Glu), in positions 67-74 of the beta domain of DRB alleles is restricted to some DR14 alleles. Therefore, there are three possible explanations for class II allele involvement in autoantibody in PV patients with class II haplotypes marked by HLA-DR14. First, the class II alleles could be markers for an unidentified susceptibility gene in linkage disequilibrium with them. Second, the primary association could be with DQB1*0503 and the association with HLA-DR14 alleles would be the result of linkage disequilibrium. Third, the HLA-DRB1 locus susceptibility could involve a specific amino acid sequence in the third hypervariable region shared by several HLA-DR14 alleles.

Cicatricial pemphigoid (CP) is a chronic autoimmune blistering disease affecting multiple mucous membranes derived from stratified squamous epithelium and occasionally the skin. CP has a wide spectrum of disease manifestations. Patients with oral pemphigoid (OP) have a benign self-limited disease in which pathological changes are restricted to the oral mucosa. On the other hand, patients with ocular cicatricial pemphigoid (OCP), a chronic condition marked with relapses and remissions, have ocular involvement and also perhaps involvement of other mucous membranes. AU clinical subsets are characterized by the presence of a similar antibasement zone autoantibody. The factors that determine the development of one form of CP or the other are not known. In a previous study, we described the asiation between OCP and the DQBI*0301 allele (P = 0.006). In this study, we have analyzed 22 Caucasian patients with OP and their family members for major histocompatibility complex DRB generic, DQA1, and DQBI allele associations by PCR-sequence-speciflc oligonucleotide probe hybridization. The results were compared to those obtained from 17 Cancasian patients with OCP and to control Caucasian alleles and haplotypes. The DQBI*0301 allele frequency was 38.6% in OP, 52.9% in OCP, and 17.8% in controls. Statistically siificant associations were detected between the DQB1*0301 allele and both OP (P = 0.0047) and OCP (P < 0.0001). In addition, DRB1*04 showed a statistically significant association (P = 0.005) with OCP when compared to controls. Analysis of major histocompatibility complex class H haplotypes showed sgfant statistical associations between both OCP and OP and the HLA-DRB1*04, DRB4*0101, DQA1*03, DQB1*0301 haplotype (P < 0.0001 and P = 0.0012, respectively). Our results indicate that DQBJ*0301 is a marker of both oral and ocular forms of CP. The analysis ofthe amino acid sequence oftheDQBl alleles present in both OP and OCP suggested that amino acid residues at position 57 and positions 71-77 may also be markers of CP.Cicatricial pemphigoid (CP) is an autoimmune blistering disease that involves multiple mucous membranes and occasionally the skin (1). The pathogenesis is attributed to the deposition in vivo of an anti-basement membrane antibody and complement leading to blister formation and subsequent progressive subepithelial fibrosis (2). CP has various clinical manifestations. When only the oral mucosa (oral pemphigoid, OP) is involved, the condition is usually benign and selflimited. In contrast, ocular CP (OCP) frequently involves other mucous membranes and has severe clinical manifestations and a chronic course requiring the use of high doses of corticosteroids and immunosuppressive agents to prevent blindness.In previous studies, we showed (3) an association between theDQBl *0301 allele and OCP (P < 0.003; relative risk = 9.6) when compared to a large population of healthy normal Caucasians. In that study, 19 out of 20 OCP patients carried DQ7 (DQBI*0301) (3). In addition, the presence ofHLA DQ7 was not due t...

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