Sequence analysis of the HLA-DR beta and HLA-DQ beta loci from three Pemphigus vulgaris patients.

Pemphigus vulgaris (PV) is an autoimmune dermatologic disease that has been associated with the HLA serotypes DR4 and DRw6. In studying this association at the level of coding sequence polymorphism, we have determined the nucleotide sequences of the second variable exons from the HLA-DR beta and DQ beta loci from three PV patients with the HLA serotypes DR4/4, DR4/5, and DR4/5. These exons were enzymatically amplified by polymerase chain reaction (PCR) and cloned directly into an M13 vector for DNA sequencing. Analyses of amino acid sequences translated from the nucleotide sequence data show that all three patients contained a DR4 DR beta I sequence associated with the Dw10 DR4 subtype specificity, a relatively rare subtype among U.S. Caucasian DR4 haplotypes. The DQ beta sequence from three of the four DR4 haplotypes was identical to the sequence (DQB3.2) found on 60-80% of control DR4 haplotypes. These observations suggest that the amino acid residues at position 68, 69, and 72 of the DR beta I chain that distinguish Dw10 from the other DR4 subtypes may be involved in disease susceptibility.