A new model for dermatitis herpetiformis that uses HLA-DQ8 transgenic NOD mice.
Dermatitis herpetiformis (DH) is an autoimmune blistering skin disorder that is associated with gluten sensitivity. It presents as a papulovesicular rash and is often associated with enteropathy. The rash resolves when the patient is placed on a gluten-free diet and/or dapsone. DH, as well as celiac disease, is tightly associated with DQ2 and DQ8. A novel mouse model for DH is described that utilizes the NOD background and the HLA-DQ8 transgene. The addition of DQ8 contributes sensitivity to gliadin, and the addition of the NOD background contributes to autoimmunity and pathogenesis. Fifteen NOD DQ8+ mice of 90 that were sensitized to gluten developed blistering pathology similar to that seen in DH. Neutrophil infiltration of the dermis, deposition of IgA at the dermal-epidermal junction, and a complete reversal of the blistering phenomenon with the administration of a gluten-free diet with or without dapsone were observed. None of the 3 blistering mice examined had small-bowel pathology. This animal model of DH will be useful to determine the specificity of the IgA deposits, as well as the pathogenic mechanisms that occur in the skin as a result of gluten ingestion.
Marietta
Eric
E
Department of Immunology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Black
Kay
K
Camilleri
Michael
M
Krause
Patricia
P
Rogers
Roy S
RS
David
Chella
C
Pittelkow
Mark R
MR
Murray
Joseph A
JA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D003622:Dapsone / Q000627:therapeutic use; D003874:Dermatitis Herpetiformis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004032:Diet; D004195:Disease Models, Animal; D004423:Ear / Q000033:anatomy & histology / Q000473:pathology; D005903:Gliadin / Q000276:immunology; D005983:Glutens / Q000008:administration & dosage / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D011503:Transglutaminases / Q000378:metabolism; D021182:Wheat Hypersensitivity / Q000276:immunology / Q000503:physiopathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D007070:Immunoglobulin A; D005983:Glutens; D003622:Dapsone; D005903:Gliadin; D011503:Transglutaminases