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Allergy Asthma Immunol Res. Nov 2012; 4(6): 332–340.
Published online Jun 25, 2012. doi:  10.4168/aair.2012.4.6.332
PMCID: PMC3479226
Most Highly Cytokinergic IgEs Have Polyreactivity to Autoantigens
Jun-ichi Kashiwakura,1,2 Yoshimichi Okayama,2 Masutaka Furue,3 Kenji Kabashima,4 Shinji Shimada,5 Chisei Ra,2 Reuben P. Siraganian,6 Yuko Kawakami,1 and Toshiaki Kawakamicorresponding author1
1Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
2Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, Itabashi-ku, Tokyo, Japan.
3Department of Dermatology, Kyushu University, Fukuoka, Japan.
4Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan.
5Department of Dermatology, University of Yamanashi, Yamanashi, Japan.
6Receptors and Signal Transduction Section, OIIB, National Institute for Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
corresponding authorCorresponding author.
Correspondence to: Toshiaki Kawakami, MD, PhD, Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA. Tel: +1-858-752-6814; Fax: +1-858-752-6986; toshi/at/liai.org
Present address: Department of Dermatology, Kyoto University, Kyoto, Japan.
Received February 6, 2012; Revised April 13, 2012; Accepted May 2, 2012.
Abstract
Purpose
Monomeric IgE molecules, when bound to the high-affinity receptor, exhibit a vast heterogeneity in their ability to induce survival promotion and cytokine production in mast cells. At one end of this spectrum, highly cytokinergic (HC) IgEs can induce potent survival promotion, degranulation, cytokine production, migration, etc., whereas at the other end, poorly cytokinergic (PC) IgEs can do so inefficiently. In this study, we investigated whether IgEs recognize autoantigens and whether IgEs' binding of autoantigens correlates with difference s in HC versus PC properties.
Methods
Enzyme-linked immunosorbent assays were performed to test whether IgEs bind antigens. Histamine-releasing factor in human sera was quantified by western blotting. Cultured mast cells derived from human cord blood were used to test the effects of human sera on cytokine production.
Results
Most (7/8) of mouse monoclonal HC IgEs exhibited polyreactivity to double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), β-galactosidase, thyroglobulin and/or histamine-releasing factor. By contrast, mouse PC IgEs failed to react with these antigens. A human monoclonal HC IgE also showed polyreactivity to histamine-releasing factor, dsDNA and ssDNA. Interestingly, sera from atopic dermatitis patients showed increased reactivity to ssDNA and β-galactosidase and increased levels of histamine-releasing factor. Some atopic dermatitis patients, but not healthy individuals, had substantial serum levels of HRF-reactive IgE. Sera from atopic dermatitis patients with high titers of DNA-reactive IgE could induce several fold more IL-8 secretion in human mast cells than sera from healthy individuals.
Conclusions
The results show that most HC, but not PC, IgEs exhibit polyreactivity to autoantigens, supporting the autoimmune mechanism in the pathogenesis of atopic dermatitis.
Keywords: Atopic dermatitis, mast cell, cytokine, IgE, autoantigen, histamine-releasing factor
Articles from Allergy, Asthma & Immunology Research are provided here courtesy of
Korean Academy of Asthma, Allergy and Clinical Immunology and Korean Academy of Pediatric Allergy and Respiratory Disease