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

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.

Key words: Atopic eczema, autoreactivity, self-antigens, IgE, mediator release, atopic dermatitis

Abbreviations used: AE, Atopic eczema, AP, Alkaline phosphatase, eIF6, Eukaryotic translation initiation factor 6, Hom s, Homo sapiens IgE-binding self-antigens, MnSOD, Manganese superoxide dismutase, ORF, Open reading frame