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Human Eosinophils Express the High Affinity IgE Receptor, FcεRI, in Bullous Pemphigoid
Journal article   Open access   Peer reviewed

Human Eosinophils Express the High Affinity IgE Receptor, FcεRI, in Bullous Pemphigoid

Kelly N Messingham, Heather M Holahan, Alexandra S Frydman, Colleen Fullenkamp, Rupasree Srikantha and Janet A Fairley
PloS one, Vol.9(9), pp.e107725-e107725
2014
DOI: 10.1371/journal.pone.0107725
PMCID: PMC4177878
PMID: 25255430
url
https://doi.org/10.1371/journal.pone.0107725View
Published (Version of record) Open Access

Abstract

Bullous pemphigoid (BP) is an autoimmune blistering disease mediated by autoantibodies targeting BP180 (type XVII collagen). Patient sera and tissues typically have IgG and IgE autoantibodies and elevated eosinophil numbers. Although the pathogenicity of the IgE autoantibodies is established in BP, their contribution to the disease process is not well understood. Our aims were two-fold: 1) To establish the clinical relationships between total and BP180-specific IgE, eosinophilia and other markers of disease activity; and 2) To determine if eosinophils from BP patients express the high affinity IgE receptor, FcεRI, as a potential mechanism of action for IgE in BP. Our analysis of 48 untreated BP patients revealed a correlation between BP180 IgG and both BP180 IgE and peripheral eosinophil count. Additionally, we established a correlation between total IgE concentration and both BP180 IgE levels and eosinophil count. When only sera from patients (n = 16) with total IgE≥400 IU/ml were analyzed, BP180 IgG levels correlated with disease severity, BP230 IgG, total circulating IgE and BP180 IgE. Finally, peripheral eosinophil count correlated more strongly with levels of BP180 IgE then with BP180 IgG. Next, eosinophil FcεRI expression was investigated in the blood and skin using several methods. Peripheral eosinophils from BP patients expressed mRNA for all three chains (α, β and γ) of the FcεRI. Surface expression of the FcεRIα was confirmed on both peripheral and tissue eosinophils from most BP patients by immunostaining. Furthermore, using a proximity ligation assay, interaction of the α- and β-chains of the FcεRI was observed in some biopsy specimens, suggesting tissue expression of the trimeric receptor form in some patients. These studies provide clinical support for the relevance of IgE in BP disease and provide one mechanism of action of these antibodies, via binding to the FcεRI on eosinophils.
 Eosinophils - metabolism Autoantibodies - blood Cell Count Humans Middle Aged RNA, Messenger - genetics Gene Expression Regulation Male Receptors, IgE - genetics Organ Specificity RNA, Messenger - metabolism Eosinophils - immunology Pemphigoid, Bullous - genetics Autoantibodies - immunology Immunoglobulin E - immunology Pemphigoid, Bullous - blood Immunoglobulin G - immunology Aged, 80 and over Female Aged Eosinophils - cytology Receptors, IgE - blood Pemphigoid, Bullous - immunology Cohort Studies

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