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Pemphigus vulgaris in Jewish patients is associated with HLA-A region genes: mapping by microsatellite markers

Pemphigus vulgaris (PV) is the most severe autoimmune blistering disorder of the skin that is mediated by circulating autoantibodies against desmoglein 3 (Dsg3). It has been reported that in Jews the associated haplotype in PV is human leukocyte antigen (HLA) B38, DRB1*0402, DQB1*0302. Significant associations with HLA were observed also in non-Jews. Dsg3-specific T-cell responses were detected in PV patients but also in healthy individuals who were either carriers of the PV-associated DRB1*0402 allele or alleles that share similar or identical peptide binding motifs to DRB1*0402. This suggests that genes other than the classical major histocompatibility complex (MHC) genes are associated with the development of the autoimmune response. We used 16 microsatellite probes that span the entire MHC region to screen DNA samples from 38 PV patients and 76 healthy controls. Results demonstrated that some markers were associated with class II region including a TAP associated marker. However, four probes, D6S265, C_527, D6S510, and MOGC, which are all mapped to the region of HLA-A, were highly associated with PV. These results suggest that a gene, or genes in the class I region are important in the initiation of the autoimmune cascade. Activation/suppression of these genes might act as the trigger mechanism that starts the autoimmune destructive process.


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The P/P Registry has been approved by the Western Institutional Review Board (WIRB) and is actively enrolling participants.