HLA association with dermatitis herpetiformis is accounted for by a cis or transassociated DQ heterodimer.
HLA-DR, DQ, and DP restriction fragment genotyping was undertaken in 23 dermatitis herpetiformis patients and 53 healthy control subjects. HLA-DQw2 was present in 100% of patients with dermatitis herpetiformis (23 of 23) versus 40% of control subjects (21 of 53). Significant secondary associations occurred with HLA-DR3 (91% of patients versus 28% of control subjects) and DPw1 (39% of patients versus 11% of control subjects). Dermatitis herpetiformis and coeliac disease thus share an identical HLA class II association. It is likely that HLA class II genes directly influence the immune responses leading to mucosal damage in both diseases. The strongest candidate for disease susceptibility to dermatitis herpetiformis is DQw2. The HLA molecule most likely to be involved in coeliac disease is a specific DQ alpha/DQ beta heterodimer, encoded in cis arrangement in DR3 haplotypes or in trans arrangement in a DR5, 7 genotype. Our data on dermatitis herpetiformis patients fits this model perfectly. All these patients are capable of expressing this molecule, which may be responsible for the gluten sensitive enteropathy seen in a subgroup of patients with dermatitis herpetiformis and coeliac disease.
Molecular Immunogenetics Laboratory, United Medical School, Guy's Hospital, London.
M A
MA
Hall
J S
JS
Lanchbury
W J
WJ
Bolsover
K I
KI
Welsh
P J
PJ
Ciclitira
D002446:Celiac Disease / Q000235:genetics; D003874:Dermatitis Herpetiformis / Q000235:genetics*; D004198:Disease Susceptibility; D005838:Genotype; D006682:HLA-DP Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics; D015803:HLA-DR3 Antigen / Q000235:genetics; D006801:Humans; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D006684:HLA-DR Antigens; D015803:HLA-DR3 Antigen