Trapping IgE in a closed conformation by mimicking CD23 binding prevents and disrupts FcεRI interaction, 2018, Laursen, Spillner et al

[Andy]

Abstract

Anti-IgE therapeutics interfere with the ability of IgE to bind to its receptors on effector cells. Here we report the crystal structure of an anti-IgE single-domain antibody in complex with an IgE Fc fragment, revealing how the antibody inhibits interactions between IgE and the two receptors FcεRI and CD23. The epitope overlaps only slightly with the FcεRI-binding site but significantly with the CD23-binding site. Solution scattering studies of the IgE Fc reveal that antibody binding induces a half-bent conformation in between the well-known bent and extended IgE Fc conformations. The antibody acts as functional homolog of CD23 and induces a closed conformation of IgE Fc incompatible with FcεRI binding. Notably the antibody displaces IgE from both CD23 and FcεRI, and abrogates allergen-mediated basophil activation and facilitated allergen binding. The inhibitory mechanism might facilitate strategies for the future development of anti-IgE therapeutics for treatment of allergic diseases.

Open access at https://www.nature.com/articles/s41467-017-02312-7

Article on study: New research can put an end to allergic reactions

Researchers have found a new mechanism in which an antibody can prevent allergic reactions in a broad range of patients. It is a scientific breakthrough, which could pave the way for a far more effective allergy medicine.

Researchers have discovered a new approach for antibody-based treatment of allergy and asthma. It is nothing less than a breakthrough that could have a major impact on development of new medicine in years to come.

There was great excitement in the laboratory when researchers from Aarhus University recently discovered the unique mechanisms of an antibody that blocks the immune effect behind allergic reactions.

The team of researchers from the Departments of Engineering and Molecular Biology and Genetics together with German researchers from Marburg/Giessen has now described the molecular structure and mechanisms of action of the antibody, and the results are surprising.

They were hoping to find new methods to improve existing treatment, but instead they identified how a specific antibody is apparently able to completely inactivate the allergic processes.
The antibody interacts in a complex biochemical process in the human body by which it prevents the human allergy antibody (IgE) from attaching to cells, thus keeping all allergic symptoms from occurring.

http://ingenioer.au.dk/en/current/n...esearch-can-put-an-end-to-allergic-reactions/

 

[Trish]

This sounds amazing, but of course it's only worked on cells in a lab so far, it will take ages to test it on animals and then humans.