An Overview of the Effects of anti-IgE Therapies

Abstract

Source of support:Self financing Omalizumab, a humanized mAb that binds to the CH3 domain near the binding site for the high-affinity type-I IgE Fc receptors of human IgE, can neutralize free IgE and inhibit the IgE allergic pathway without sensitizing mast cells and basophils. We found that omalizumab in patients with severe persistent asthma (SPA) was an effective therapy for asthma and the following co-morbid conditions: chronic urticaria (CU), bee venom allergy, latex allergy, atopic dermatitis, food allergy and Samter's syndrome. Information on the use of omalizumab in treatment of asthma and other allergic diseases has improved our understanding that treatment acts on many levels, including regulating levels of inflammatory proteins, including cytokines (copper-containing alpha-2-glycoprotein, total antioxidant capacity, MDA, NO, H 2 O 2 , CXCL8, IL-10, TGF-b, GMCSF, IL-17, IL-1b), MPV, Hs-CRP, eosinophil cationic peptide, vitamin-D (25(OH)D), homocysteine (Hcy), OX-2, d-dimer, albumin, and sApo-2L. The decrease in Hcy concentrations and increase in 25(OH)D also support the existence of a vascular endothelial protection mechanism. Mediators and cells classically involved in pro-coagulant and anticoagulant pathways together play a role in SPA and CU pathophysiology and omalizumab effect. The mechanism of action of omalizumab in the treatment of asthma is believed to be multifactorial, and includes effects mediated through altered production of redox metabolites, extrinsic coagulation pathway, oxidative markers-related mi RNA, TRAIL-related mi RNA, and regulation of production of known inflammatory proteins BackgroundOmalizumab -anti-immunoglobulin E (IgE) -is approved for the treatment of severe allergic asthma. In addition to asthma, Omalizumab has been investigated in various other conditions, including chronic urticaria (CU), perennial and seasonal allergic rhinitis (AR), latex allergy, peanut allergy, idiopathic anaphylaxis, hyper-IgE syndrome, chronic rhinosinusitis, interstitial cystitis, aspirin sensitivity, mastocytosis, eosinophilic gastroenteritis, and atopic dermatitis [1,2]. Omalizumab -a humanized mAb that binds to the CH3 domain near the binding site for the high-affinity type-I IgE Fc receptors of human IgE -can neutralize free IgE and inhibit the IgE allergic pathway without sensitizing mast cells and basophils. It is conceivable that mast cells residing in the nasal lining, lower airway, other areas of the mucosal tracts, and in the skin, differ in tryptase and chymase content, sensitivity, receptor regulation, and life span [3][4][5][6][7][8]. The development of Omalizumab therapy over the past 20 years provides an interesting example of the emergence of a conceptually new, biotechnologyproduced pharmaceutical [8]. Omalizumab and IgE ReceptorsThe potential for Omalizumab to exert anti-inflammatory effects in patients with asthma arises from its ability to target the interaction between IgE and IgE receptors (FceRI and FceRII), thereby preventing inflammatory cell activation and interrupti...

Nordic consensus statement on the systematic assessment and management of possible severe asthma in adults

“…Anti-IgE treatment with omalizumab, a well-studied humanized recombinant IgG 1 monoclonal antibody with multiple mechanisms of action beyond binding free IgE [112], is an option in severe asthmatics with confirmed perennial allergies (pets or mites). In patients with severe allergic asthma, the add-on treatment with omalizumab has been shown to reduce the risk of exacerbations [113–117], the asthma symptoms [113,114,116,118], and the use of OCS [118] and ICS [115], as well as to improve the quality of life and lung function [113,114,116], without significant safety concerns.…”

Current challenges and controversies in the management of chronic spontaneous urticaria

“…However, such effects require 3-4 weeks to occur, at least on mast cells, which is a far longer time than the few days needed to see the decrease in urticaria severity score. In fact, omalizumab exerts a number of other effects [68], not least on the coagulation pathway where it leads to a marked reduction of D-dimer plasma levels [69] in a way similar to heparin [68]. Notably, some studies have shown the clinical efficacy of anticoagulant therapy in patients with CSU [45][46][47][48]70].…”

Severe asthma: anti-IgE or anti-IL-5?

“…Omalizumab interferes with the inflammatory cascade by reducing serum IgE levels and FcɛRI receptor expression on key cells. This results in the inhibition of the release of inflammatory mediators from mast cells and diminished recruitment of inflammatory cells, especially eosinophils, into the airways (13–16). …”