Study of the association between human leukocyte antigens (HLA) and pemphigus vulgaris in Brazilian patients.

BACKGROUND

Pemphigus vulgaris is a mucocutaneous blistering autoimmune disease that manifests as painful blisters or erosions on the skin and/or mucosal surfaces. IgG autoantibodies target desmoglein, playing a major role in disease pathogenesis. Genetic predisposal to pemphigus vulgaris, especially the HLA DR and DQ alleles, has been known since the 1980s. The unique constitution of the Brazilian population favors exploratory genetic studies.

METHODS

The study group included 51 patients with a confirmed diagnosis of pemphigus vulgaris from a tertiary hospital in Sao Paulo city, Sao Paulo, southeast Brazil. DNA was extracted from peripheral blood, and HLA A, B, C, DR, and DQ typing was performed. The control group was composed of a database of 297 deceased donors from the city of São Paulo typed with the same method. The statistical significance level was adjusted using the Bonferroni correction depending on the phenotypic frequencies evaluated for HLA A, HLA B, HLA C, HLA DRB1, DQA1, and HLA DQB1.

RESULTS

The alleles HLA-B57, HLA-C15, HLA-DRB104:02, HLA-DRB108:04, HLA-DRB114:01, DQA103:01, DQB103:02, and DQB105:03 were associated with susceptibility. Alleles HLA DRB104:02 and HLA-DRB114:01 and their respective haplotypes DRB104-DQA103:01-DQB103:02, and DRB114-DQA101:01-DQB105:03 conferred a risk of the disease.

CONCLUSIONS

The DRB104:02 and DQB105:03 alleles are associated with pemphigus vulgaris in our study as well as in various populations. The association with HLA-DRB108:04 in our study was confirmed to be specific to this allele and not to linkage disequilibrium to any adjacent gene. The association between HLA-B57 and pemphigus vulgaris is reported for the first time in the present study.