A COMMON MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II ALLELE HLA-DQB1-ASTERISK-0301 IS PRESENT IN CLINICAL VARIANTS OF PEMPHIGOID

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disea se seen primarily in elderly persons. It is characterized clinically b y the development of tense bullae and by the presence of an antibaseme nt membrane antibody. In BP, the antigens involved in the autoimmunity are epidermal basement membrane peptides BPAg1 and BPAg2. We have com pared high resolution typing of major histocompatibility complex class II loci (HLA-DRB1, DQB1) in 21 patients with BP, 17 with ocular cicat ricial pemphigoid (OCP), and 22 with oral pemphigoid (OP) to a panel o f 218 haplotypes of normal individuals. We found that the three diseas es (BP, OCP, and OP have significant association with DQB10301 (P = 0 .005, P < 0.0001, and P = 0.001, respectively). The frequencies of all eles DQB10302, *0303, and *06, which share a specific amino acid sequ ence from position 71 to 77 (Thr-Arg-Ala-Glu-Leu-Val-Thr) were also in creased (P = 0.01). We suggest that an identical major histocompatibil ity complex class II allele (DQB10301) is a common marker for enhance d susceptibility and that the same amino acid residues in positions 71 -77 (DQB10301, -0302, -0305, -0602, -0603 alleles) are found in patie nts with BP, OCP, and OP. Our findings propose that the autoimmune res ponse in the three different clinical variants of pemphigoid, involves the recognition by T cells of a class II region of DQB1, bound to a p eptide from the basement membrane of conjunctiva, oral mucosa, and ski n.