Mucous membrane pemphigoid: HLA-DOB1∗0301 is associated with all clinical sites of involvement and may be linked to antibasement membrane IgG production. Setterfield J, Theron J, Vaughan RW, Welsh KI, Mallon E, Wojnarowska F, Challacombe SJ, Black MM. Br J Dermatol 2001;145:406–414

Abstract

Class I human leukocyte antigens (HLA)-A, -B, -Cw and class II HLA-DRB1, -DQB1 alleles were determined in 131 British Caucasian patients with mucous membrane pemphigoid (MMP) using serological and DNA-based methods. The authors analyzed the class I and II alleles expressed in well-defined clinical and immunopathological subgroups of MMP, in order to establish whether specific alleles or haplotypes might in part explain disease susceptibility, clinical sites of involvement, or disease severity. Subgroups of patients were analyzed according to the following clinical criteria: age of onset, sex, sites of clinical involvement (oral, ocular, skin, nasal, genital, pharyngeal, esophageal, laryngeal, perianal), disease severity, and history of autoimmune disease. Subgroups were also analyzed according to the following immunopathological criteria: autoantibody profile, the presence of circulating antibasement membrane IgG or IgA antibodies and the detection of target basement membrane zone (BMZ) antigens (BP230 and BP180) by IgG autoantibodies. Class I HLA typing showed no significant disease or subgroup associations. Class II DRB1 typing showed a significantly increased allelic frequency in MMP vs controls for DRB1∗11. For DQB1, MMP vs controls, there was a significantly increased allelic frequency for DQB1∗0301 in both males and females; all clinical sites of involvement, with the exception of laryngeal, esophageal and perianal sites and in patients with detectable circulating anti-BMZ IgG compared with those negative for IgG. A positive trend was noted in patients with ocular involvement compared with no ocular involvement and in patients with a clinical score greater than or equal to 10 compared with <10. We found no difference in DQB1∗0301 allele frequency between subgroups with or without BP180 or BP230 target antigens. Haplotype frequencies showed an increase in DRB1∗04, DQB1∗0301 and DRB1∗11, DQB1∗0301 among patients compared with controls. The authors conclude that the DQB1∗0301 allele confers a predisposition to all subgroups of MMP and may have a role in T-cell recognition of basement membrane antigens, resulting in the production of anti-BMZ IgG autoantibodies. The positive trend between increased allelic expression of DQB1∗0301 in patients with ocular disease and in those with a higher clinical score, further suggests a role for this allele in disease severity.—Thomas J. Liesegang