HLA-DRB1 AND HLA-DQB1 GENES IN SUSCEPTIBILITY AND RESISTANCE TO CICATRICIAL PEMPHIGOID IN FRENCH CAUCASIANS

Cicatricial pemphigoid (CP) is a chronic, autoimmune, subepithelial bl istering disease, characterized by the presence of antibasement membra ne antibodies (BMZ) against anchoring filaments components. An associa tion between the HLA-DQB10301 allele and ocular cicatricial pemphigoi d has been previously reported in North American Caucasians. In this s tudy, we compared high resolution typing HLA-DRB1 and -DQB1 alleles in 25 CP patients (50 haplotypes) with 106 geographically matched, healt hy controls (212 haplotypes), who were all French Caucasians, As in Am erican 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 DQB10301 allele (Pc = 7 x 10(-5); RR = 4.23). HLA-DQB1*0301 is i n linkage disequilibrium with several DRB1 alleles. Only the DRB11101 DQB10301 haplotype frequency was significantly increased (24.0% in C P, 6.6% in control, Pc = 0.002). Furthermore. we observed a decrease o f 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 sign ificant decreased frequency of the DRB10701 DQB1*0202 haplotype (0% i n CP vs 12.7%, Pc = 0.07 PC) and a non-significant decrease of DRB103 01 DQB10201 (4% in CP vs 12.3%). HLA-DQB1*0301 encodes a negative cha rge at position DQ beta 57 (Asp), a critical position in peptide bindi ng 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.