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Unraveling the significance of IgE autoantibodies in organ-specific autoimmunity: lessons learned from bullous pemphigoid

  • IMMUNOLOGY AT THE UNIVERSITY OF IOWA
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Abstract

Bullous pemphigoid (BP), a cutaneous autoimmune blistering disease, has provided a useful model to elucidate a role for IgE in autoimmunity. IgE antibodies specific for the BP180 autoantigen are detected in sera and biopsy samples from the majority of BP patients. In BP biopsies, both IgE and BP180 antigen localize to the surface of mast cells, and incubation of circulating basophils from these patients with BP180 protein triggered degranulation. The in vivo pathogenicity of BP180-specific IgE was confirmed in mouse models, where injection of purified BP IgE into human skin grafted onto nu/nu mice replicated the early phase of lesion development, including mast cell degranulation, eosinophil infiltration and development of urticarial plaques. In addition, IgE antibodies from patient sera bind to BP180 on basal keratinocytes, resulting in internalization of BP180, production of inflammatory cytokines, IL-6 and IL-8, and a decrease in the number of hemidesmosomes at the basement membrane zone. These findings have led to therapeutic trials of the anti-IgE monoclonal antibody omalizumab in BP, resulting in substantial improvement in the patients' disease. Overall, the work in BP provides the first evidence for a pathogenic role for IgE in autoimmunity.

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Authors and Affiliations

  1. Department of Dermatology, University of Iowa College of Medicine, 200 Hawkins Drive, Iowa City, IA, 52242, USA

    K. A. N. Messingham, H. M. Holahan & J. A. Fairley

  2. Department of Dermatology, VA Medical Center, Iowa City, IA, USA

    J. A. Fairley

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  1. K. A. N. Messingham
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  2. H. M. Holahan
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  3. J. A. Fairley
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Correspondence to J. A. Fairley.

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Messingham, K.A.N., Holahan, H.M. & Fairley, J.A. Unraveling the significance of IgE autoantibodies in organ-specific autoimmunity: lessons learned from bullous pemphigoid. Immunol Res 59, 273–278 (2014). https://doi.org/10.1007/s12026-014-8547-7

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