COMMON MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MARKERS IN CLINICAL VARIANTS OF CICATRICIAL PEMPHIGOID

Cicatricial pemphigoid (CP) is a chronic autoimmune blistering disease affecting multiple mucous membranes derived from stratified squamous epithelium and occasionally the skin. CP has a wide spectrum of diseas e manifestations, Patients with oral pemphigoid (OF) have a benign sel f-limited disease in which pathological changes are restricted to the oral mucosa. On the other hand, patients with ocular cicatricial pemph igoid (OCP), a chronic condition marked with relapses and remissions, have ocular involvement and also perhaps involvement of other mucous m embranes. All clinical subsets are characterized by the presence of a similar antibasement zone autoantibody. The factors that determine the development of one form of CP or the other are not known. In a previo us study, we described the association between OCP and the DQB10301 a llele (P = 0.006). In this study, we have analyzed 22 Caucasian patien ts with OP and their family members for major histocompatibility compl ex DRB generic, DQA1, and DQB1 allele associations by PCR-sequence-spe cific oligonucleotide probe hybridization. The results were compared t o those obtained from 17 Caucasian patients with OCP and to control Ca ucasian alleles and haplotypes. The DQB10301 allele frequency was 38. 6% in OP, 52.9% in OCP, and 17.8% in controls. Statistically significa nt associations were detected between the DQB10301 allele and both OP (P 0.0047) and OCP (P < 0.0001). In addition, DRB104 showed a statis tically significant association (P = 0.005) with OCP when compared to controls. Analysis of major histocompatibility complex class II haplot ypes showed significant statistical associations between both OCP and OP and the HLA-DRB104, DRB4*0101, DQA1*03, DQB1*0301 haplotype (P < 0 .0001 and P = 0.0012, respectively). Our results indicate that DQB103 01 is a marker of both oral and ocular forms of CP. The analysis of th e amino acid sequence of the DQB1 alleles present in both OP and OCP s uggested that amino acid residues at position 57 and positions 71-77 m ay also be markers of CP.