Immunoglobulin E and Allergy: Antibodies in Immune Inflammation and Treatment

Abstract

The pathogenic role of immunoglobulin E (IgE) antibodies in triggering and maintaining allergic inflammation in response to allergens is due to the binding of multivalent allergens to allergen-specific IgEs on sensitized effector cells. These interactions trigger effector cell activation, resulting in release of potent inflammatory mediators, recruitment of inflammatory cells, antigen presentation, and production of allergen-specific antibody responses. Since its discovery in the 1960s, the central role of IgE in allergic disease has been intensively studied, placing IgE and its functions at the heart of therapeutic efforts for the treatment of allergies. Here, we provide an overview of the nature, roles, and significance of IgE antibodies in allergic diseases, infections, and inflammation and the utility of antibodies as therapies. We place special emphasis on allergen-IgEFcε receptor complexes in the context of allergic and inflammatory diseases and describe strategies, including monoclonal antibodies, aimed at interrupting these complexes. Of clinical significance, one antibody, omalizumab, is presently in clinical use and works by preventing formation of IgE-Fcε receptor interactions. Active immunotherapy approaches with allergens and allergen derivatives have also demonstrated clinical benefits for patients with allergic diseases. These treatments are strongly associated with serum increases of IgE-neutralizing antibodies and feature a notable redirection of humoral responses towards production of antibodies of the IgG4 subclass in patients receiving immunotherapies. Lastly, we provide a new perspective on the rise of recombinant antibodies of the IgE class recognizing tumor-associated antigens, and we discuss the potential utility of tumor antigen-specific IgE antibodies to direct potent IgE-driven immune responses against tumors.

Association of Interleukin-4 in Immunoglobulin-E Mediated Asthma: A Cross Sectional Study

“…These interactions trigger effector cell activation, releasing potent inflammatory mediators, recruitment of inflammatory cells, antigen presentation, and production of allergen-specific antibody responses. 14 These events may cause responses at a local level, such as bronchoconstriction, vasodilation, and/or airway mucus secretion, and trigger the allergy-associated symptoms of nasal congestion, wheezing, sneezing, and cough, conjunctivitis, runny nose, dyspnoea, and chest tightness. 15 This study was conducted to examine the evidence for the effect of Th2 cytokine (IL-4) and total IgE on asthma severity and to investigate the possible ability of asthma control to reduce IL-4 levels and total IgE.…”

Therapeutic Monoclonal Antibodies against Cancer: Present and Future

“…In addition, other Ig classes (IgA, IgE, or IgM) are being evaluated as anti-cancer therapeutic antibodies. For example, the therapeutic possibilities of an IgEbased immunotherapy [69,[73][74][75][76], including its safety [71,77], have been analyzed in renal carcinoma [67], breast cancer [68], ovarian cancer [78], and melanoma [79] models. All these analyses showed that the IgE was more effective than the corresponding IgG1 antibody.…”