Most highly cytokinergic IgEs have polyreactivity to autoantigens

Jun Ichi Kashiwakura, Yoshimichi Okayama, Masutaka Furue, Kenji Kabashima, Shinji Shimada, Chisei Ra, Reuben P. Siraganian, Yuko Kawakami, Toshiaki Kawakami

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)332-340
Number of pages9
JournalAllergy, Asthma and Immunology Research
Volume4
Issue number6
DOIs
Publication statusPublished - Nov 1 2012

Fingerprint

Atopic Dermatitis
Immunoglobulin E
Serum
Mast Cells
Galactosidases
Single-Stranded DNA
Autoantigens
Cytokines
Antigens
Survival
Thyroglobulin
Interleukin-8
Fetal Blood
To autoantigen
Cultured Cells
Western Blotting
Enzyme-Linked Immunosorbent Assay
translationally-controlled 1 tumor protein
DNA

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pulmonary and Respiratory Medicine

Cite this

Kashiwakura, J. I., Okayama, Y., Furue, M., Kabashima, K., Shimada, S., Ra, C., ... Kawakami, T. (2012). Most highly cytokinergic IgEs have polyreactivity to autoantigens. Allergy, Asthma and Immunology Research, 4(6), 332-340. https://doi.org/10.4168/aair.2012.4.6.332

Most highly cytokinergic IgEs have polyreactivity to autoantigens. / Kashiwakura, Jun Ichi; Okayama, Yoshimichi; Furue, Masutaka; Kabashima, Kenji; Shimada, Shinji; Ra, Chisei; Siraganian, Reuben P.; Kawakami, Yuko; Kawakami, Toshiaki.

In: Allergy, Asthma and Immunology Research, Vol. 4, No. 6, 01.11.2012, p. 332-340.

Research output: Contribution to journalArticle

Kashiwakura, JI, Okayama, Y, Furue, M, Kabashima, K, Shimada, S, Ra, C, Siraganian, RP, Kawakami, Y & Kawakami, T 2012, 'Most highly cytokinergic IgEs have polyreactivity to autoantigens', Allergy, Asthma and Immunology Research, vol. 4, no. 6, pp. 332-340. https://doi.org/10.4168/aair.2012.4.6.332
Kashiwakura, Jun Ichi ; Okayama, Yoshimichi ; Furue, Masutaka ; Kabashima, Kenji ; Shimada, Shinji ; Ra, Chisei ; Siraganian, Reuben P. ; Kawakami, Yuko ; Kawakami, Toshiaki. / Most highly cytokinergic IgEs have polyreactivity to autoantigens. In: Allergy, Asthma and Immunology Research. 2012 ; Vol. 4, No. 6. pp. 332-340.
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