title: Most Highly Cytokinergic IgEs Have Polyreactivity to Autoantigens.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA. ; Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, Itabashi-ku, Tokyo, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Kashiwakura
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Okayama
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimada
authors.forename: Chisei
authors.initials: C
authors.lastname: Ra
authors.forename: Reuben P
authors.initials: RP
authors.lastname: Siraganian
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kawakami
keywords: Atopic dermatitis; IgE; autoantigen; cytokine; histamine-releasing factor; mast cell