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Omalizumab and isotypes

Bianca Balbino, Eva Conde, Thomas Marichal, Philipp Starkl, Laurent L Reber
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...
June 15, 2018: Pharmacology & Therapeutics
Krzysztof Kowal, Pawel Bielecki, Ilona V DuBuske, Lawrence M DuBuske
AIM: The aim of this study was to evaluate the potential of anti-immunoglobulin E (IgE) and/or anti-IgE-IgE immune complexes to release histamine from peripheral blood basophils. In addition, a potential modulating effect of anti-IgE-IgE complexes on allergen-induced peripheral blood basophil histamine release was evaluated. METHODS: Whole blood basophil histamine release (WBB-HR) tests done by using glass-fiber-based microtiter plates were performed in 62 patients with allergic rhinitis and/or asthma sensitized to perennial allergens...
May 1, 2017: Allergy and Asthma Proceedings:
Toshiaki Kawakami, Ulrich Blank
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...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Nina van Beek, Franziska S Schulze, Detlef Zillikens, Enno Schmidt
Autoimmune bullous diseases (AIBDs) are characterized by autoantibodies against structural proteins of the dermal-epidermal junction (in pemphigoid diseases) and the epidermal/ epithelial desmosomes (in pemphigus diseases). By far, the most common AIBD is bullous pemphigoid, which is immunopathologically characterized by autoantibodies against BP180 (type XVII collagen) and BP230. IgG and, to a lesser extent, IgA autoantibodies are the major autoantibody isotypes in these disorders. IgE autoantibodies are increasingly reported in particular in bullous pemphigoid...
2016: Expert Review of Clinical Immunology
Dana L Baker, Gerald R Nakamura, Henry B Lowman, Saloumeh Kadkhodayan Fischer
Omalizumab (Xolair®) is a recombinant humanized monoclonal antibody that selectively binds to human immunoglobulin E (IgE). Omalizumab is used to treat IgE-mediated diseases such as chronic idiopathic urticaria (CIU) and moderate to severe allergic asthma. In pre-marketing clinical trials in patients with asthma, anaphylaxis was reported in 3 of 3,507 (0.1%) patients. In post-marketing spontaneous reports, the frequency of anaphylaxis attributed to omalizumab use was estimated to be at least 0.2% of patients based on an estimated exposure of about 57,300 patients from June 2003 through December 2006...
January 2016: AAPS Journal
Yuling Wu, Xu Liu, Yan Chen, Robert Woods, Nancy Lee, Harry Yang, Partha Chowdhury, Lorin K Roskos, Wendy I White
To address a possible linkage between the occurrence of the hypersensitivity reactions and the induction of IgE anti-drug-antibodies (ADA), a drug specific IgE ADA assay was developed using electrochemiluminescence (ECL) technology. In the assay a drug-specific IgE isotype chimeric antibody was generated and used as an ADA positive control. The biotinylated drug X (an antibody) and ruthenium-labeled omalizumab (an anti-human IgE antibody) were used as capture and detection reagents, respectively. The binding affinities of the chimeric IgE isotype positive control have been shown to be highly comparable to drug X and drug Y (drug X is the 2nd generation of drug Y), indicating that it could serve as a highly useful control to compare and contrast the relative ability of the two generations of drug to elicit IgE ADA responses...
December 2013: Journal of Pharmaceutical and Biomedical Analysis
Seung Y Chu, Holly M Horton, Erik Pong, Irene W L Leung, Hsing Chen, Duc-Hanh Nguyen, Cristina Bautista, Umesh S Muchhal, Matthew J Bernett, Gregory L Moore, David E Szymkowski, John R Desjarlais
BACKGROUND: Sequestration of IgE to prevent its binding to high-affinity IgE receptor FcεRI on basophils and mast cells is an effective therapy for allergic asthma. IgE production requires differentiation of activated IgE(+) B cells into plasma cells upon allergen sensitization. B-cell receptor signaling is suppressed by the inhibitory IgG Fc receptor FcγRIIb; therefore, we reasoned that a therapeutic antibody that coengages FcγRIIb and IgE B-cell receptor would not only sequester IgE but also suppress its production by blocking IgE(+) B-cell activation and differentiation to IgE-secreting plasma cells...
April 2012: Journal of Allergy and Clinical Immunology
Gennaro D'Amato, Enrica Bucchioni, Virginio Oldani, Walter Canonica
Bronchial asthma is a chronic inflammatory disease of the airways which is recognized as a highly prevalent health problem in both the developed and the developing world, with significant human and economic consequences.Allergy is acknowledged as a major risk factor for asthma. The pathogenetic aspects of allergic asthma are characterized by airway inflammation with infiltration of mast cells, basophils, eosinophils, monocytes and T helper type 2 lymphocytes, along with the isotype switching of B cells to generate immunoglobulins of the immunoglobulin E (IgE) class...
2006: Treatments in Respiratory Medicine
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