HLA class II region genes and susceptibility to dermatitis herpetiformis: DPB1 and TAP2 associations are secondary to those of the DQ subregion

Classical dermatitis herpetiformis (DH) is associated with similar HLA class I, II and III polymorphisms to coeliac disease (CD). The two diseases share distinctive pathological changes to the small intestinal mucosa which reverse on withdrawal of dietary gluten. In order to determine the locus primarily associated with DH, and to examine whether there is a common genetic link predisposing to the enteropathy seen in both DH and coeliac disease, HLA-DR, DQ and DP subregion associations were investigated by HLA genotyping in 23 DH patients and 64 healthy controls. We also studied polymorphisms of the TAP2 locus, which is located between the DP and DQ subregions. Genotyping was carried out by PCR of genomic DNA with allelic assignment by sequence-specific oligonucleotide (SSO) hybridization or amplification refractory mutation system (ARMS). The strongest associations in the patient group were with HLA DRB1*0301 (91% vs 22% of controls), HLA DQB1*02 (100% vs 32% of controls) and DPB1*0101 (39% and 14%). These associations are similar to those described for CD. 100% of DH patients were positive for the DQA1*0501/DQB1*02 dimer in cis or trans and, by analogy with CD, this is probably responsible for presenting gliadin peptide implicated in the disease process. Homozygosity for DQ2 was significantly increased in the CD patient group compared to the DH patient group (65% versus 39%), and so differences in dosage of HLA class II genotypes between DH and CD may be responsible for the milder gastrointestinal symptoms characteristic of DH.