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