Alterations in HLA-DP and HLA-DQ antigen frequency in patients with dermatitis herpetiformis.

Dermatitis herpetiformis (DH) is associated with a markedly increased frequency of the HLA class II antigens DR3 and DQw2. To investigate a possible role of HLA-DP (or closely associated genes) in the pathogenesis of DH as well as to confirm the previously described alterations of HLA-DR3 and HLA-DQw2 antigen frequency, we have typed 43 patients with DH for HLA-DP, HLA-DQ, and HLA-DR antigens. All patients with DH had typical clinical and histologic features, as well as granular deposits of IgA at the dermal-epidermal junction by direct immunofluorescence. HLA-DR3 was expressed in 41 of 43 (95%) DH patients, whereas HLA-DQw2 was expressed in all 43 (100%). The overall distribution of HLA-DP antigens in patients with DH was significantly different from that seen in all controls and in HLA-DR3 and HLA-DQw2 controls (p less than 0.02). Examination of the frequency of individual DP antigens revealed that HLA-DPw1 was increased (42% of patients with DH vs 11% of all controls and 26% of DR3 positive controls), but this increase was not statistically greater than that expected due to the disequilibrium linkage of DPw1 with DR3/DQw2. Patients with DH, however, did have a statistically significant decreased frequency of DPw2 (14% of patients vs 31% of all controls and 41% of DR3 positive controls) (pc less than 0.05). Studies of three informative families demonstrated that the DPw2 genes of the DH patients were not present on the haplotype thought to carry a DH susceptibility gene (HLA-A1, HLA-B8, HLA-DR3, HLA-DQw2). A role of HLA-DP region genes in the pathogenesis of DH is further suggested by the observation that HLA-DPw1 was expressed in 82% (9 of 11) of DH patients with IgA antibodies against dietary antigens as compared with only 33% (4 of 12) of patients without IgA antibodies. HLA-DP genes or genes closely linked to them may be important in DH either as markers of the disease haplotype or by direct involvement in its pathogenesis.