HLA-DRB1 and HLA-DQB1 genes in susceptibility and resistance to cicatricial pemphigoid in French Caucasians.
Cicatricial pemphigoid (CP) is a chronic, autoimmune, subepithelial blistering disease, characterized by the presence of antibasement membrane antibodies (BMZ) against anchoring filaments components. An association between the HLA-DQB1*0301 allele and ocular cicatricial pemphigoid has been previously reported in North American Caucasians. In this study, we compared high resolution typing HLA-DRB1 and -DQB1 alleles in 25 CP patients (50 haplotypes) with 106 geographically matched, healthy controls (212 haplotypes), who were all French Caucasians. As in American Caucasians, we confirmed a positive association of CP with the HLA-DQB1*0301 allele which was present in 54% of CP haplotypes (27/50); by contrast 21.7% (46/212) of the matched normal individuals carried the DQB1*0301allele (Pc = 7 x 10(-5); RR = 4.23). HLA-DQB1*0301 is in linkage disequilibrium with several DRB1 alleles. Only the DRB1*1101 DQB1*0301 haplotype frequency was significantly increased (24.0% in CP, 6.6% in control, Pc = 0.002). Furthermore, we observed a decrease of the frequency of the DQB1*02 allele (6% vs 25% in the control group, Pc = 0.05; RR = 0.19). The negative association corresponds to a significant decreased frequency of the DRB1*0701 DQB1*0202 haplotype (0% in CP vs 12.7%, Pc = 0.07 PC) and a non-significant decrease of DRB1*0301 DQB1*0201 (4% in CP vs 12.3%). HLA-DQB1*0301 encodes a negative charge at position DQ 57 (Asp), a critical position in peptide binding to the HLA-DQ molecule groove and therefore we speculate that this molecule may play a role in the selection of BMZ peptides in CP.
Drouet
M
M
Department of Dermatology, University Hospital Debré, Reims, France.
Delpuget-Bertin
N
N
Vaillant
L
L
Chauchaix
S
S
Boulanger
M D
MD
Bonnetblanc
J M
JM
Bernard
P
P
D000483:Alleles; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D005802:Genes, MHC Class II; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D010390:Pemphigoid, Benign Mucous Membrane / Q000235:genetics* / Q000276:immunology; D044465:White People / Q000235:genetics
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen