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

Full 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.

Author information

Author/s: Zeller, Sabine (S); Rhyner, Claudio (C); Meyer, Norbert (N); Schmid-Grendelmeier, Peter (P); Akdis, Cezmi A (CA); Crameri, Reto (R);

Affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Validation Studies

Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol), published in United States. (Language: eng)

Reference: 2009-Aug; vol 124 (issue 2) : pp 278-85, 285.e1-7

Dates: Created 2009/08/03; Completed 2009/09/08;

PMID: 19541355, status: MEDLINE (last retrieval date: 9/8/2009, IMS Date: )

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