IgE, IgE Receptors and Anti-IgE Biologics: Protein Structures and Mechanisms of Action

Abstract

The evolution of IgE in mammals added an extra layer of immune protection at body surfaces to provide a rapid and local response against antigens from the environment. The IgE immune response employs potent expulsive and inflammatory forces against local antigen provocation, at the risk of damaging host tissues and causing allergic disease. Two well-known IgE receptors, the high-affinity FcεRI and low-affinity CD23, mediate the activities of IgE. Unlike other known antibody receptors, CD23 also regulates IgE expression, maintaining IgE homeostasis. This mechanism evolved by adapting the function of the complement receptor CD21. Recent insights into the dynamic character of IgE structure, its resultant capacity for allosteric modulation, and the potential for ligand-induced dissociation have revealed previously unappreciated mechanisms for regulation of IgE and IgE complexes. We describe recent research, highlighting structural studies of the IgE network of proteins to analyze the uniquely versatile activities of IgE and anti-IgE biologics. Expected final online publication date for the Annual Review of Immunology, Volume 41 is April 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The Very Low IgE Producer: Allergology, Genetics, Immunodeficiencies, and Oncology

“…The anaphylactic function of IgE is dependent on Fc-epsilon receptor I molecules (CD23) on the surfaces of the degranulating cells and the IgE master with Fc-epsilon receptor I as a complex biological system that has also been called the 'IgE-network' [46]. This system provides a defense mechanism against infections and toxins [47], but a consensus on whether this is the most relevant function of this Ig isotype has never been reached. Multiple epidemiological studies have described inverse associations between allergic diseases and malignancies [48,49] and led to the hypothesis-supported by experimental studies on animal models [50]-that IgE may be involved in antitumor surveillance, an area of investigation purposedly denominated 'allergo-oncology' [51].…”

Expanding the Anti-Phl p 7 Antibody Toolkit: An Anti-Idiotype Nanobody Inhibitor

“…Plots of kobs versus concentration showed the expected linearity for both HAPPID1 Fab and HAPPIE1 Fab (Supplementary Figure S2B,C), indicating that the induced dissociation phenomenon Unusually, we observed a downturn in association curves at the highest concentrations for the HAPPID1 Fab or HAPPIE1 Fab interactions with captured aδNb072. This appears to be due to a small amount of induced dissociation [36], where Fab binding to aδNb072 slightly destabilizes the interaction between the aδNb072 His-tag and the capturing anti-Histag antibody. Consequently, fits of association curves were only performed before binding plateaued (as shown in Supplementary Figure S2A).…”

Dupilumab’s Impact on Blood Parameters in Nasal Polyposis: 18-Month Follow-Up in Real Life

“…Monoclonal antibodies (Mabs) may act on type 2 inflammatory response in several ways: by targeting the IL-5 pathways (mepolizumab or benralizumab) [12][13][14], neutralizing the IgE-mediated response (omalizumab) [15], and acting against IL-4 and IL-13 signaling (dupilumab) [16,17], demonstrating, the three drugs mentioned, efficacy in the treatment of CRSwNP [18][19][20][21][22].…”