A new model for dermatitis herpetiformis that uses HLA-DQ8 transgenic NOD mice.

Abstract

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.

• Authors: Eric Marietta, Kay Black, Michael Camilleri, Patricia Krause, Roy S Rogers 3rd, Chella David, Mark R Pittelkow, Joseph A Murray
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 114 Issue 8 Pg. 1090-7 (Oct 2004) ISSN: 0021-9738 [Print] United States
• PMID: 15489956 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• HLA-DQ Antigens
• HLA-DQ8 antigen
• Immunoglobulin A
• Glutens
• Dapsone
• Gliadin
• Transglutaminases

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Dapsone (therapeutic use)
• Dermatitis Herpetiformis (drug therapy, genetics, immunology, pathology)
• Diet
• Disease Models, Animal
• Ear (anatomy & histology, pathology)
• Gliadin (immunology)
• Glutens (administration & dosage, immunology)
• HLA-DQ Antigens (genetics, metabolism)
• Humans
• Immunoglobulin A (metabolism)
• Intestine, Small (cytology, metabolism)
• Mice
• Mice, Inbred NOD
• Mice, Transgenic
• Skin (cytology, metabolism, pathology)
• Transglutaminases (metabolism)
• Wheat Hypersensitivity (immunology, physiopathology)