The binding site on human immunoglobulin E for its high affinity receptor

Presta, Leonard G.; Shields, Robert L.; O'Connell, Lori; Lahr, Steven J.; Porter, Jason R.; Gorman, Cornelia M.; Jardieu, Paula

doi:10.1016/s0021-9258(18)47203-1

Cited by 170 publications

(36 citation statements)

References 39 publications

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“…IgE is an important potential key component targeted at the early stage of hypersensitive reaction as it leads to the activation of other chemical or immunological cascades in later stages. These antibodies, in turn, attached to specific receptors on other resident cells by binding to high-affinity (cεRI) surface receptors on basophils, mast cells or CD23 on B lymphocytes and eosinophils (Presta et al, 1994). IgE has a short half-life and thus having lower concentration compared to other immunoglobulins in the circulation.…”

Section: Suppression Of Immunoglobulin Ementioning

confidence: 99%

Anti-Allergic Rhinitis Effects of Medicinal Plants and Their Bioactive Metabolites via Suppression of the Immune System: A Mechanistic Review

et al. 2021

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Allergic rhinitis (AR) is a common inflammatory condition of the nasal mucosa and it is an immunoglobulin E–mediated disease. The incidence and prevalence of AR globally have been escalating over recent years. Antihistamines, intranasal corticosteroids, decongestants, intranasal anticholinergics, intranasal cromolyn, leukotriene receptor antagonists and immunotherapy have been used in the treatment of AR. However, there is a need to search for more effective and safer remedies as many of the current treatments have reported side effects. Medicinal plants have been used traditionally to relief symptoms of AR but their efficacy and safety have not been scientifically proven. In this review, up-to-date reports of studies on the anti-allergic rhinitis of several medicinal plants and their bioactive metabolites through suppression of the immune system are compiled and critically analyzed. The plant samples were reported to suppress the productions of immunoglobulin E, cytokines and eosinophils and inhibit histamine release. The suppression of cytokines production was found to be the main mechanistic effect of the plants to give symptomatic relief. The prospect of these medicinal plants as sources of lead molecules for development of therapeutic agents to treat AR is highlighted. Several bioactive metabolites of the plants including shikonin, okicamelliaside, warifteine, methylwarifteine, luteolin-7-O-rutinoside, tussilagone, petasin, and mangiferin have been identified as potential candidates for development into anti-allergic rhinitis agents. The data collection was mainly from English language articles published in journals, or studies from EBSCOHOST, Medline and Ovid, Scopus, Springer, and Google Scholar databases from the year 1985–2020. The terms or keywords used to find relevant studies were allergic rhinitis OR pollinosis OR hay fever, AND medicinal plant OR single plant OR single herb OR phytotherapy. This comprehensive review serves as a useful resource for medicinal plants with anti-allergic rhinitis potential, understanding the underlying mechanisms of action and for future exploration to find natural product candidates in the development of novel anti-allergic rhinitis agents.

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Section: Suppression Of Immunoglobulin Ementioning

confidence: 99%

Anti-Allergic Rhinitis Effects of Medicinal Plants and Their Bioactive Metabolites via Suppression of the Immune System: A Mechanistic Review

et al. 2021

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“…60 Because omalizumab specifically interacts with the Cε3 domain, that includes the IgE binding sites for both FcεRIs and FcεRIIs/CD23, this humanized antibody impedes IgE linkage to highaffinity and low-affinity receptors, thus preventing all IgE-mediated cellular events involved in asthma pathobiology. 60,61 Hence, at the level of mast cells and basophils, omalizumab inhibits antigen-triggered degranulation (Figure 1), and also prevents the release of eicosanoids and the synthesis of cytokines/chemokines induced by FcεRI activation. In addition, omalizumab is also thought to be capable of abrogating mast cell functions which do not depend on IgE The humanized monoclonal antibody omalizumab binds to free human IgE, thus inducing the generation of immune complexes which impede the interactions between IgE and its receptors.…”

Section: Mechanism Of Action Of Omalizumabmentioning

confidence: 99%

Omalizumab, the first available antibody for biological treatment of severe asthma: more than a decade of real-life effectiveness

Pelaia

Calabrese

Terracciano

et al. 2018

Ther Adv Respir Dis

109

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Omalizumab was the first, and for a long time the only available monoclonal antibody for the add-on treatment of severe allergic asthma. In particular, omalizumab selectively targets human immunoglobulin (Ig)E, forming small-size immune complexes that inhibit IgE binding to its high- and low-affinity receptors. Therefore, omalizumab effectively blunts the immune response in atopic asthmatic patients, thus significantly improving the control of asthma symptoms and successfully preventing disease exacerbations. These very positive effects of omalizumab make it possible to drastically decrease both referrals to the emergency room and hospitalizations for asthma exacerbations. Such important therapeutic actions of omalizumab have been documented by several randomized clinical trials, and especially by more than 10 years of real-life experience in daily clinical practice. Omalizumab can also interfere with airway remodelling by inhibiting the activation of IgE receptors located on structural cells such as bronchial epithelial cells and airway smooth muscle cells. Moreover, omalizumab is characterized by a very good safety and tolerability profile. Hence, omalizumab represents a valuable therapeutic option for the add-on biological treatment of severe allergic asthma.

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“…30,31 Because the binding site of omalizumab is buried within the Fc3RI receptor, it cannot bind to IgE that is already attached to mast cells and basophils. 32,33 Consequently, Figure 1 The GINA guidelines recommend a stepwise approach to controller medication based on level of control. Figure 2 Proposed mechanisms of action of omalizumab.…”

Section: Omalizumab Mechanism Of Actionmentioning

confidence: 99%

The use of omalizumab in the treatment of severe allergic asthma: A clinical experience update

Holgate

Buhl²,

Bousquet

et al. 2009

Respiratory Medicine

109

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Severe persistent asthma causes a substantial morbidity and mortality burden and is frequently inadequately controlled despite intensive guideline-based therapy. Targeting allergic inflammatory processes that underlie the pathogenesis of severe persistent asthma improves asthma control in a significant proportion of patients. Omalizumab, a humanized monoclonal anti-immunoglobulin E (IgE) antibody, has been developed to target IgE, which is central to triggering and maintaining allergic airway inflammation. In a comprehensive program of clinical trials, omalizumab has been shown to reduce asthma exacerbation and emergency visit rates, and to improve quality of life in patients with severe persistent allergic asthma. It is difficult to predict which patients would most benefit from omalizumab treatment; accurate selection and dosing of patients are essential to achieve benefit. Patients need to have convincing IgE-mediated asthma and be dosed according to pre-treatment serum total IgE level and body weight, using a specified dosing table. Based on clinical trial data analysis, it is recommended that treatment response is evaluated by the physician after 16 weeks of therapy. Treatment should only be continued in responders, i.e. those judged by the physician to have achieved a marked improvement or complete asthma control. Omalizumab is generally well tolerated. Anaphylactic-like reactions are rare (0.1% of patients) and less common than encountered with other biologics.

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The binding site on human immunoglobulin E for its high affinity receptor

Cited by 170 publications

References 39 publications

Anti-Allergic Rhinitis Effects of Medicinal Plants and Their Bioactive Metabolites via Suppression of the Immune System: A Mechanistic Review

Anti-Allergic Rhinitis Effects of Medicinal Plants and Their Bioactive Metabolites via Suppression of the Immune System: A Mechanistic Review

Omalizumab, the first available antibody for biological treatment of severe asthma: more than a decade of real-life effectiveness

The use of omalizumab in the treatment of severe allergic asthma: A clinical experience update

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