Approaches to target IgE antibodies in allergic diseases

Abstract

IgE is the antibody isotype found at the lowest concentration in the circulation. However IgE can undeniably play an important role in mediating allergic reactions; best exemplified by the clinical benefits of anti-IgE monoclonal antibody (omalizumab) therapy for some allergic diseases. This review will describe our current understanding of the interactions between IgE and its main receptors FcεRI and CD23 (FcεRII). We will review the known and potential functions of IgE in health and disease: in particular, its detrimental roles in allergic diseases and chronic spontaneous urticaria, and its protective functions in host defense against parasites and venoms. Finally, we will present an overview of the drugs that are in clinical development or have therapeutic potential for IgE-mediated allergic diseases.

The mechanistic and functional profile of the therapeutic anti-IgE antibody ligelizumab differs from omalizumab

“…A s a key driver in the development and manifestation of hypersensitivity reactions against normally nonhazardous substances, immunoglobulin E (IgE) has become a major target of therapeutic intervention strategies [1][2][3] . IgE is known to interact with two major receptors, FcεRI and CD23/FcεRII 4 , which are involved in different immunological processes 5 .…”

The anti-IgE mAb omalizumab induces adverse reactions by engaging Fcγ receptors

“…IgE antibodies (Abs) are key mediators of allergic diseases (1)(2)(3). Upon exposure to an allergen in allergic patients, such allergen is recognized by IgE bound to the high-affinity receptor FcεRI on the surface of mast cells and basophils, which promotes the immediate activation of these cells and the release of inflammatory mediators such as histamine, responsible for allergic symptoms (3).…”

Influence of prolonged treatment with omalizumab on the development of solid epithelial cancer in patients with atopic asthma and chronic idiopathic urticaria: A systematic review and meta‐analysis

“…Immunoglobulin E (IgE) is known to play a key role in mediating atopic Th2‐associated conditions, including atopic asthma and chronic idiopathic urticaria (CIU) . IgE‐bearing cells are found in the nasal or bronchial mucosa during the sensitization phase to aeroallergens and this sets the stage for their activation during subsequent allergen exposure . When an antigen binds to the IgE variable regions of two adjacent IgE antibodies on a mast cell, their receptors become physically cross‐linked.…”

“…The subsequent uptake of calcium ions leads to degranulation and release of pro‐inflammatory mediators such as histamine, tryptase, leukotrienes and prostaglandins . These mediators are responsible for the symptoms of an immediate allergic reaction and can also contribute to late reactions that occur 4 to 8 hours after an immediate response …”