Significantly increased occurrence of HLA-DQB1*0301 allele in patients with ocular cicatricial pemphigoid.

To determine the immunogenetic characteristics of patients with immune-mediated subepithelial blistering diseases of mucous membranes, we performed HLA-typing for the class II MHC gene DQB1*0301 allele using a direct method. Genomic DNA extracted from Caucasian patients was amplified by polymerase chain reaction using primer pairs specific for the DQB loci followed by Southern blotting with a peroxidase-conjugated sequence-specific oligonucleotide probe. Seventy-six percent (16/21) of patients with ocular mucosal disease (with or without oral mucosal and skin diseases) carried the DQB1*0301 allele; by contrast, only 33% (14/42) of race-, age-, and geography-matched normal individuals carried the DQB1*0301 allele (p < 0.005). The relative risk for ocular disease if DQB1*0301 allele is present is 6.4, similar to the relative risk of 8 for patients with ocular but no oral disease (pure ocular cicatricial pemphigoid, p < 0.025). In patients with oral mucosal disease (with or without ocular mucosal and skin diseases), 68% (15/22) carried the DQB1*0301 allele (p < 0.025). When patients with ocular disease were excluded, however, the increased occurrence of the DQB1*0301 allele in patients with oral disease was not statistically significant (64%, 7/11, p < 0.25). In patients with subepidermal blistering skin disease but no oral or ocular disease, there was no increase in the occurrence of the DQB1*0301 allele (38%, 5/13, p > 0.5). The significantly increased occurrence of the DQB1*0301 allele in patients with ocular mucosal disease may point to a distinct immunogenetic factor that predisposes patients to develop an ocular scarring process.