Antigen-independent effects of immunoglobulin E

Abstract

Immunoglobulin E (IgE) is an important mediator in immediate hypersensitivity, as it facilitates mast cell degranulation and the release of immunomodulatory mediators, such as histamine, prostaglandins, and cytokines. Antigen-specific IgE is a hallmark of allergic diseases. Upon interaction with polyvalent antigen, IgE molecules crosslink and transmit signals that drive this process. Recently, an alternative function of IgE has come to light. Rather than merely priming the mast cell, in the absence of antigen, IgE influences mast cells, including their survival, receptor expression, and mediator release. The mechanisms by which IgE induces these effects and the biological consequences are being discovered and are showing that IgE has an important and active role in facilitating immune responses.

Allergic Mechanisms in Eosinophilic Esophagitis

“…Additionally, there are a number of antigen-independent immune functions of IgE, which include enhancement of mast cell survival, maintenance of mast cell location, and dendritic cell migration. 82 Clinical studies have documented the presence of allergen-specific IgE in patients with EoE, and skin prick testing (SPT) is commonly abnormal, providing evidence of immediate hypersensitivity to a variety of foods, and specific IgE has been suggested to contribute to symptoms. 40 Interestingly, a clinical study of omalizumab, a monoclonal antibody directed against IgE, in the treatment of EoE, found clinical but not histologic or endoscopic improvement.…”

Beyond immediate hypersensitivity: evolving roles for IgE antibodies in immune homeostasis and allergic diseases

“…In further contrast to the DNP‐ε‐206 clone, the SPE‐7 antibody elevated expression of Bcl‐X L , a mitochondrial protein that inhibits apoptosis, and prevented the DNA fragmentation associated with apoptosis (81). Follow‐up work showed a spectrum of activities for different IgE antibodies, with a general correlation between the ability to induce FcεR1 aggregation and replication of signaling events typically induced by classical IgE and antigen crosslinking (63, 83). It is unclear why some IgE antibodies are more potent than others and how IgE aggregates FcεR1 in the absence of antigen.…”

Direct effects of IL-4 on mast cells drive their intestinal expansion and increase susceptibility to anaphylaxis in a murine model of food allergy

“…5 There is considerable evidence that in addition to serving as effector cells of allergy, mast cells participate in the afferent limb of immune responses by facilitating activation of antigen-presenting cells, and exerting a range of effects on regulatory T cells and integrity of mucosal barriers. 7–9 Defining the factors that regulate intestinal mast cell expansion and effector functions in the intestine is of great importance and might guide the development of novel strategies for the regulation of immune responses to foods. In the current study we focus on the direct cell intrinsic effects of IL-4 receptor signals on intestinal mast cells.…”