title: Common major histocompatibility complex class II markers in clinical variants of cicatricial pemphigoid.
abstract: 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 disease manifestations. Patients with oral pemphigoid (OP) have a benign self-limited disease in which pathological changes are restricted to the oral mucosa. On the other hand, patients with ocular cicatricial pemphigoid (OCP), a chronic condition marked with relapses and remissions, have ocular involvement and also perhaps involvement of other mucous membranes. All clinical subsets are characterized by the presence of a similar anti-basement zone autoantibody. The factors that determine the development of one form of CP or the other are not known. In a previous study, we described the association between OCP and the DQB1*0301 allele (P = 0.006). In this study, we have analyzed 22 Caucasian patients with OP and their family members for major histocompatibility complex DRB generic, DQA1, and DQB1 allele associations by PCR-sequence-specific oligonucleotide probe hybridization. The results were compared to those obtained from 17 Caucasian patients with OCP and to control Caucasian alleles and haplotypes. The DQB1*0301 allele frequency was 38.6% in OP, 52.9% in OCP, and 17.8% in controls. Statistically significant associations were detected between the DQB1*0301 allele and both OP (P = 0.0047) and OCP (P < 0.0001). In addition, DRB1*04 showed a statistically significant association (P = 0.005) with OCP when compared to controls. Analysis of major histocompatibility complex class II haplotypes showed significant statistical associations between both OCP and OP and the HLA-DRB1*04, DRB4*0101, DQA1*03, DQB1*0301 haplotype (P < 0.0001 and P = 0.0012, respectively). Our results indicate that DQB1*0301 is a marker of both oral and ocular forms of CP. The analysis of the amino acid sequence of the DQB1 alleles present in both OP and OCP suggested that amino acid residues at position 57 and positions 71-77 may also be markers of CP.
authors.affiliation: Division of Immunogenetics, Dana-Farber Cancer Institute, Boston, MA 02115.
authors.forename: J J
authors.initials: JJ
authors.lastname: Yunis
authors.forename: N
authors.initials: N
authors.lastname: Mobini
authors.forename: E J
authors.initials: EJ
authors.lastname: Yunis
authors.forename: C A
authors.initials: CA
authors.lastname: Alper
authors.forename: R
authors.initials: R
authors.lastname: Deulofeut
authors.forename: A
authors.initials: A
authors.lastname: Rodriguez
authors.forename: C S
authors.initials: CS
authors.lastname: Foster
authors.forename: D
authors.initials: D
authors.lastname: Marcus-Bagley
authors.forename: R A
authors.initials: RA
authors.lastname: Good
authors.forename: A R
authors.initials: AR
authors.lastname: Ahmed
mesh_terms: D015342:DNA Probes; D005128:Eye Diseases / Q000235:genetics; D005802:Genes, MHC Class II / Q000235:genetics*; D005819:Genetic Markers; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D009059:Mouth Diseases / Q000235:genetics; D009693:Nucleic Acid Hybridization; D010390:Pemphigoid, Benign Mucous Membrane / Q000235:genetics*; D010391:Pemphigoid, Bullous / Q000235:genetics; D016133:Polymerase Chain Reaction; D044465:White People
chemical_list: D015342:DNA Probes; D005819:Genetic Markers; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens