IgE-mediated mechanisms in bullous pemphigoid and other autoimmune bullous diseases

Figures & data

Figure 1. Clinical presentations of bullous pemphigoid. Tense blisters on normal skin (A), tense blisters on erythematous and normal skin (B+D), prurigo-like bullous pemphigoid (C), and urticarial lesions (E).

Figure 2. Lesional histolopathology in bullous pemphigoid. 20x magnification (A). 40x magnification (B). e, epidermis; d, dermis; i, inflammatory infiltrate with lymphocytes and numerous eosinophils (arrows).

Table 1. Important references.

Reference number	author	year	title	summary
[3]	Schmidt E, Zillikens D.	2013	Pemphigoid diseases.	This review outlines epidemiology, diagnostics, clinical aspects, and treatment options in bullous pemphigoid
[37]	Fairley JA et al.	2009	Pathogenicity of IgE in autoimmunity: Successful treatment of bullous pemphigoid with omalizumab	This article represents the first demonstration of the in vivo pathogenicity of IgE class autoantibodies in a steroid-unresponsive BP patient.
[45]	Dimson OG et al.,	2003	Identification of a Potential Effector Function for IgE Autoantibodies in the Organ-Specific Autoimmune Disease Bullous Pemphigoid	This article shows BP180-specific IgE-mediated degranulation of basophils, thus direct evidence of IgE pathogenicity in BP.
[46]	Dresow SK et al.	2009	IgE autoantibodies against the intracellular domain of BP180.	In this article, a fine-mapping of both IgG and IgE reactivity is reported and both immunoglobulin classes mainly target the NC16A domain of BP180.
[71]	Bushkell LL, Jordon RE.	1983	Bullous pemphigoid: a cause of peripheral blood eosinophilia.	One of the first studies discovering eosinophilia as a feature of BP
[77]	Messingham KN et al.	2014	Human Eosinophils Express the High Affinity IgE Receptor, FcεRI, in Bullous Pemphigoid.	This study shows the relevance of eosinophils and their link to IgE reactivity in BP
[82]	Provost TT, Tomasi TB.	1974	Immunopathology of bullous pemphigoid. Basement membrane deposition of IgE, alternate pathway components and fibrin.	This is the first report of tissue-bound IgE in BP
[83]	Yayli S et al	2011	Detection of linear IgE deposits in bullous pemphigoid and mucous membrane pemphigoid: a useful clue for diagnosis.	This study related deposition of IgE autoantibodies in the skin to the clinical phenotype of BP
[93]	Fairley JA et al.	2007	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	This mouse model describes the pathogenicity of IgE anti-BP180 autoantibodies in the early phase of BP.
[96]	Döpp et al.,	2000	IgG4 and IgE are the major immunoglobulins targeting the NC16A domain of BP180 in Bullous pemphigoid: serum levels of these immunoglobulins reflect disease activity.	This is the first report of IgE reactivity against the immunodominat NC16A domain of BP180 in a substantial number of BP patients and the correlation of serum levels of anti-BP180 NC16A IgE with disease activity.
[114]	Messingham KAN et al.	2012	Functional Characterization of an IgE-Class Monoclonal Antibody Specific for the Bullous Pemphigoid Autoantigen, BP180.	Here, cytokine secretion of cultured keratinocytes in response to antihuman IgE NC16A is shown.
[122]	Zone JJ et al.	2007	IgE Basement Membrane Zone Antibodies Induce Eosinophil Infiltration and Histological Blisters in Engrafted Human Skin on SCID Mice.	This mouse model describes the role of IgE anti-BP180 autoantibodies in immunocompromised mice with a monoclonal antibody.

Schmidt E, Zillikens D. Pemphigoid diseases. Lancet. 2013;381(9863):320–332.

 PubMed Web of Science ®Google Scholar

Fairley JA, Baum CL, Brandt DS, et al. Pathogenicity of IgE in autoimmunity: Successful treatment of bullous pemphigoid with omalizumab. J Allergy Clin Immunol. 2009;123(3):704–705.

 PubMed Web of Science ®Google Scholar

Dimson OG, Giudice GJ, Fu CL, et al. Identification of a potential effector function for IgE autoantibodies in the organ-specific autoimmune disease bullous pemphigoid. J Invest Dermatol. 2003;120(5):784–788.

 PubMed Web of Science ®Google Scholar

Dresow SK, Sitaru C, Recke A, et al. IgE autoantibodies against the intracellular domain of BP180. Br J Dermatol. 2009;160(2):429–432.

 PubMed Web of Science ®Google Scholar

Bushkell LL, Jordon RE. Bullous pemphigoid: a cause of peripheral blood eosinophilia. J Am Acad Dermatol. 1983;8(5):648–651.

 PubMed Web of Science ®Google Scholar

Messingham KN, Holahan HM, Frydman AS, et al. Human eosinophils express the high affinity IgE receptor, FcεRI, in bullous pemphigoid. PLoS One. 2014;9(9):e107725.

 PubMed Web of Science ®Google Scholar

Provost TT, Tomasi TB. Immunopathology of bullous pemphigoid. Basement membrane deposition of IgE, alternate pathway components and fibrin. Clin Exp Immunol. 1974;18(2):193–200.

 PubMed Web of Science ®Google Scholar

Yayli S, Pelivani N, Beltraminelli H, et al. Detection of linear IgE deposits in bullous pemphigoid and mucous membrane pemphigoid: a useful clue for diagnosis. Br J Dermatol. 2011;165(5):1133–1137.

 PubMed Web of Science ®Google Scholar

Fairley JA, Burnett CT, Fu C-L, et al. 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. J Invest Dermatol. 2007;127(11):2605–2611.

 PubMed Web of Science ®Google Scholar

Döpp R, Schmidt E, Chimanovitch I, et al. IgG4 and IgE are the major immunoglobulins targeting the NC16A domain of BP180 in Bullous pemphigoid: serum levels of these immunoglobulins reflect disease activity. J Am Acad Dermatol. 2000;42(4):577–583.

 PubMed Web of Science ®Google Scholar

Messingham KAN, Onoh A, Vanderah EM, et al. Functional characterization of an IgE-class monoclonal antibody specific for the bullous pemphigoid autoantigen, BP180. Hybridoma. 2012;31(2):111–117.

 PubMedGoogle Scholar

Zone JJ, Taylor T, Hull C, et al. IgE basement membrane zone antibodies induce eosinophil infiltration and histological blisters in engrafted human skin on SCID mice. J Invest Dermatol. 2007;127(5):1167–1174.

 PubMed Web of Science ®Google Scholar