From IgE to Omalizumab

Abstract

IgE is the least abundant Ig isotype, yet it plays a critical role in allergic reactions and host protection from helminth infection. Although IgE was discovered 50 years ago, the ultimate evidence for its role in human allergic diseases was obtained by the efficacy of anti-IgE therapy in many clinical trials on asthma and other allergic diseases. Beginning from the discovery of IgE 50 y ago, followed by studies of IgE receptors and activation mechanisms, this review provides a historic perspective of allergy research that has led to the development of anti-IgE therapy and other strategies targeting IgE and its receptors. Current IgE studies toward future precision medicine are also reviewed.

Figure 1. Timeline of IgE-related research

The major discoveries related to IgE research that led to the development of IgE-targeting therapeutics are highlighted.

Figure 2. IgE, its interaction with omalizumab, and FcεRI-mediated mast cell activation

(A) IgE and the relative locations of the FcεRIα- and CD23-binding sites. (B) Open and closed conformations of the IgE-Fcε3–4 domains interacting with FcεRIα and CD23, respectively. (C) Symmetric interaction of two omalizumab Fabs with IgE-Fcε3–4. Modified from Pennington et al. (63). (D) Crosslinking of IgE-bound FcεRI with a multivalent allergen leads to activation of mast cells. The activated cells degranulate and produce/release lipid mediators and cytokines. Signal transduction via the FcεRI was recently reviewed (–127). Domains of IgE and omalizumab are represented by ovals. ITAMs, immunoreceptor tyrosine-based activation motifs.