Mucous membrane pemphigoid: HLA-DOB1*0301 is associated with all clinical sites of involvement and may be linked to antibasement membrane IgG production

Citation
J. Setterfield et al., Mucous membrane pemphigoid: HLA-DOB1*0301 is associated with all clinical sites of involvement and may be linked to antibasement membrane IgG production, BR J DERM, 145(3), 2001, pp. 406-414
Citations number
40
Categorie Soggetti
Dermatology,"da verificare
Journal title
BRITISH JOURNAL OF DERMATOLOGY
ISSN journal
00070963 → ACNP
Volume
145
Issue
3
Year of publication
2001
Pages
406 - 414
Database
ISI
SICI code
0007-0963(200109)145:3<406:MMPHIA>2.0.ZU;2-I
Abstract
Background Class I human leucocyte antigens (HLA) -A, -B, -Cw and class II HLA-DRB1, -DQB1 alleles were determined in 131 British Caucasian patients w ith mucous membrane pemphigoid (MMP) using serological and DNA-based method s. Objectives To analyse the class I and II alleles expressed in well-defined clinical and immunopathological subgroups of MMP, in order to establish whe ther specific alleles or haplotypes might in part explain disease susceptib ility, clinical sites of involvement or disease severity. Methods Subgroups of patients were analysed according to the following clin ical criteria: age of onset, sex, sites of clinical involvement (oral, ocul ar, skin, nasal, genital, pharyngeal, oesophageal, laryngeal, perianal), di sease severity and history of autoimmune disease. Subgroups were also analy sed according to the following immunopathological criteria: autoantibody pr ofile, the presence of circulating antibasement membrane IgG or IgA antibod ies and the detection of target basement membrane zone (BMZ) antigens (BP23 0 and BP180) by IgG autoantibodies. Results Class I HLA typing showed no significant disease or subgroup associ ations. Class II DRB1 typing showed a significantly increased allelic frequ ency in MMP vs. controls for DRB1*11 (RR = 2.08, Pc < 0.0000056). For DQB1, MMP vs. controls, there was a significantly increased allelic frequency fo r DQB1*0301 (Pc < 0.00000028) in both males and females; all clinical sites of involvement, with the exception of laryngeal, oesophageal and perianal sites and in patients with detectable circulating anti-BMZ IgG compared wit h those negative for IgG (P < 0.0096, Pc < 0.019). A positive trend was not ed 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 subg roups with or without BP180 or BP230 target antigens. Haplotype frequencies showed an increase in DRB1*04, DQB1*0301 (Pc < 0.000066) and DRB1*11, DQB1 *0301 (Pc < 0.000002) among patients compared with controls. Conclusions The DQB1*0301 allele confers a predisposition to all subgroups of MMP and may have a role in T-cell recognition of basement membrane antig ens, resulting in the production of anti-BMZ IgG autoantibodies. The positi ve 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.