The Fab fragment of anti-IgE Cε2 domain prevents allergic reactions through interacting with IgE-FcεRIα complex on rat mast cells

Sci Rep. 2018 Sep 24;8(1):14237. doi: 10.1038/s41598-018-32200-z.

Abstract

Immunoglobulin E (IgE) plays a central role in the pathogenesis of Type I hypersensitivity through interaction with a high-affinity receptor (FcεRIα). For therapeutic applications, substantial attention has been focused recently on the blockade of the IgE interaction with FcεRIα. While exploring better options for preventing allergic diseases, we found that the Fab fragment of the rat anti-murine IgE antibody (Fab-6HD5) strongly inhibited passive cutaneous anaphylaxis (PCA) in vivo, as well as spleen tyrosine kinase (Syk) activity and β-hexosaminidase release from basophilic leukemia cells in vitro. The in vivo effects of Fab-6HD5 pre-administration were maintained over a long period of time for at least 10 days. Using flow cytometry analysis, we also found that Fab-6HD5 did not recognize the IgE Cε3 domain containing specific binding sites for FcεRIα. Furthermore, deletion-mapping studies revealed that Fab-6HD5 recognized conformational epitopes on the Cε2 domain of IgE. Given that the Cε2 domain plays a key role in stabilizing the interaction of IgE with FcRIα, our results suggest that the specific binding of Fab-6HD5 to the Cε2 domain prevents allergic reactions through destabilizing the preformed IgE-FcεRIα complex on rat mast cells. Although the present study was performed using animal models, these findings support the idea that a certain antibody directed against IgE CH domains may contribute to preventing allergic diseases through interacting with IgE-FcεRIα complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / immunology
  • Basophils / immunology
  • Binding Sites / immunology
  • Epitopes / immunology
  • Hexosaminidases / immunology
  • Humans
  • Hypersensitivity / genetics
  • Hypersensitivity / immunology
  • Hypersensitivity, Immediate / immunology*
  • Immunoglobulin Domains / immunology
  • Immunoglobulin Fab Fragments / genetics
  • Immunoglobulin Fab Fragments / immunology*
  • Mast Cells / immunology
  • Mice
  • Passive Cutaneous Anaphylaxis / genetics
  • Passive Cutaneous Anaphylaxis / immunology*
  • Rats
  • Receptors, IgE / genetics
  • Receptors, IgE / immunology*
  • Syk Kinase / immunology

Substances

  • Antibodies, Anti-Idiotypic
  • Epitopes
  • FCER1A protein, rat
  • Immunoglobulin Fab Fragments
  • Receptors, IgE
  • anti-IgE antibodies
  • Syk Kinase
  • Hexosaminidases