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-DQB10301 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-DQB10301 allele which was present in 54% of CP haplotypes (27/50); by contrast 21.7% (46/212) of the matched normal individuals carried the DQB10301allele (Pc = 7 x 10(-5); RR = 4.23). HLA-DQB10301 is in linkage disequilibrium with several DRB1 alleles. Only the DRB11101 DQB10301 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 DQB102 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 DRB10701 DQB10202 haplotype (0% in CP vs 12.7%, Pc = 0.07 PC) and a non-significant decrease of DRB10301 DQB10201 (4% in CP vs 12.3%). HLA-DQB10301 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.