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 di seases share distinctive pathological changes to the small intestinal mucosa which reverse on withdrawal of dietary gluten. In order to dete rmine the locus primarily associated with DH, and to examine whether t here 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 c ontrols. We also studied polymorphisms of the TAP2 locus, which is loc ated between the DP and DQ subregions. Genotyping was carried out by P CR of genomic DNA with allelic assignment by sequence-specific oligonu cleotide (SSO) hybridization or amplification refractory mutation syst em (ARMS). The strongest associations in the patient group were with H LA DRB10301 (91% vs 22% of controls), HLA DQB1*02 (100% vs 32% of con trols) and DPB10101 (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 p robably responsible for presenting gliadin peptide implicated in the d isease process. Homozygosity for DQ2 was significantly increased in th e 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 charact eristic of DH.