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Exploring the repertoire of IgE-binding self-antigens associated with atopic eczema


Zeller, S; Rhyner, C; Meyer, N; Schmid-Grendelmeier, P; Akdis, C A; Crameri, R (2009). Exploring the repertoire of IgE-binding self-antigens associated with atopic eczema. Journal of Allergy and Clinical Immunology, 124(2):278-285.e1.

Abstract

BACKGROUND: Atopic eczema (AE) is the most common chronic inflammatory skin disease. Recent data demonstrate the presence of autoreactive serum IgE antibodies correlating with the severity of the disease. OBJECTIVE: Although several IgE-binding self-antigens have been reported, the whole repertoire of IgE-binding self-antigens is unknown. We aimed to estimate the repertoire size of autoreactive proteins related to AE and clone, produce, and characterize humoral and T-cell responses against novel self-antigens. METHODS: Phage surface-displayed human cDNA libraries were enriched for clones binding to serum IgE from patients with AE and screened by using high-throughput technology. Selected clones were used to produce the encoded proteins, to test their IgE-binding ability in Western blots and ELISAs, and their ability to induce mediator release from basophils of sensitized individuals. RESULTS: One hundred forty sequences encoding potential IgE-binding self-antigens associated with AE were identified. Sixteen sequences encoded already described self-antigens. Three new sequences showed homology with environmental allergens, 86 encoded known human proteins, 7 predicted proteins, and 28 showed sequence identity with genomic contigs. Immunoblotting and ELISA experiments demonstrated the presence of IgE antibodies in sera from patients with AE to 5 selected recombinant self-antigens and their ability to induce mediator release from basophils of patients with AE who have self-antigen-specific IgE antibodies. CONCLUSION: These data demonstrate a broad spectrum of at least 140 IgE-binding self-antigens associated with AE. By binding IgE antibodies or activating specific T cells, they might promote, perpetuate, or both existing skin inflammation.

Abstract

BACKGROUND: Atopic eczema (AE) is the most common chronic inflammatory skin disease. Recent data demonstrate the presence of autoreactive serum IgE antibodies correlating with the severity of the disease. OBJECTIVE: Although several IgE-binding self-antigens have been reported, the whole repertoire of IgE-binding self-antigens is unknown. We aimed to estimate the repertoire size of autoreactive proteins related to AE and clone, produce, and characterize humoral and T-cell responses against novel self-antigens. METHODS: Phage surface-displayed human cDNA libraries were enriched for clones binding to serum IgE from patients with AE and screened by using high-throughput technology. Selected clones were used to produce the encoded proteins, to test their IgE-binding ability in Western blots and ELISAs, and their ability to induce mediator release from basophils of sensitized individuals. RESULTS: One hundred forty sequences encoding potential IgE-binding self-antigens associated with AE were identified. Sixteen sequences encoded already described self-antigens. Three new sequences showed homology with environmental allergens, 86 encoded known human proteins, 7 predicted proteins, and 28 showed sequence identity with genomic contigs. Immunoblotting and ELISA experiments demonstrated the presence of IgE antibodies in sera from patients with AE to 5 selected recombinant self-antigens and their ability to induce mediator release from basophils of patients with AE who have self-antigen-specific IgE antibodies. CONCLUSION: These data demonstrate a broad spectrum of at least 140 IgE-binding self-antigens associated with AE. By binding IgE antibodies or activating specific T cells, they might promote, perpetuate, or both existing skin inflammation.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Swiss Institute of Allergy and Asthma Research
04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2009
Deposited On:09 Feb 2010 10:00
Last Modified:18 Feb 2018 00:12
Publisher:Elsevier
ISSN:0091-6749
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.jaci.2009.05.015
PubMed ID:19541355

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