A Pathogenic Role for IgE in Autoimmunity: Bullous Pemphigoid IgE Reproduces the Early Phase of Lesion Development in Human Skin Grafted to nu/nu Mice

Janet A Fairley; Christopher T Burnett; Chang-Ling Fu; David L Larson; Matthew G Fleming; George J Giudice

doi:10.1038/sj.jid.5700958

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A Pathogenic Role for IgE in Autoimmunity: Bullous Pemphigoid IgE Reproduces the Early Phase of Lesion Development in Human Skin Grafted to nu/nu Mice

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A Pathogenic Role for IgE in Autoimmunity: Bullous Pemphigoid IgE Reproduces the Early Phase of Lesion Development in Human Skin Grafted to nu/nu Mice

Janet A Fairley, Christopher T Burnett, Chang-Ling Fu, David L Larson, Matthew G Fleming and George J Giudice

Journal of investigative dermatology, Vol.127(11), pp.2605-2611

11/2007

DOI: 10.1038/sj.jid.5700958

PMID: 17611576

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Abstract

Bullous pemphigoid (BP) is an autoimmune disease characterized by subepidermal blistering. Based on previous work, IgG autoantibodies directed against BP180 are thought to be the primary pathogenic agent in BP. In addition to these IgG autoantibodies, however, most BP patients produce IgE class autoantibodies that also react with BP180, and total IgE levels are often elevated in this disease. To directly test whether BP IgE is pathogenic, 6ng of total IgE isolated from two BP and two normal sera were injected into human skin grafted onto athymic, nude mice. Twenty-four hours after injection, erythematous, elevated plaques were observed in all human skin grafts receiving BP IgE (n=11), but not control IgE (n=9). Histologic and ultrastructural examination of the lesions showed engorgement of blood vessels and a dermal infiltrate composed of neutrophils, eosinophils, and mast cells, many of which were degranulated. At a higher dose of BP IgE (47ng), histological separation of the epidermis from the dermis was observed in two of the three grafts. The BP IgE-induced erythematous plaques were reminiscent of those clinically seen in BP. This provides early evidence of a direct demonstration of a pathogenic role for IgE class autoantibodies in a human autoimmune disease.

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Title: Subtitle: A Pathogenic Role for IgE in Autoimmunity: Bullous Pemphigoid IgE Reproduces the Early Phase of Lesion Development in Human Skin Grafted to nu/nu Mice
Creators: Janet A Fairley - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Christopher T Burnett - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Chang-Ling Fu - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
David L Larson - Department of Plastic Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Matthew G Fleming - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
George J Giudice - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Resource Type: Journal article
Publication Details: Journal of investigative dermatology, Vol.127(11), pp.2605-2611
Publisher: Elsevier Inc
DOI: 10.1038/sj.jid.5700958
PMID: 17611576
ISSN: 0022-202X
eISSN: 1523-1747
Language: English
Date published: 11/2007
Academic Unit: Dermatology
Record Identifier: 9984025682902771

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