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      Eosinophils and eosinophilic immune dysfunction in health and disease

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          Abstract

          The functions ascribed to eosinophils have classically been limited to host defence against certain parasitic infections and potentially deleterious effects in the setting of specific diseases that are associated with elevated eosinophil counts in blood and/or tissue. The ability to induce eosinophil depletion either experimentally in animal models or through targeted therapies in humans has extended our understanding of the roles played by eosinophils in health and homeostasis as well as in disease pathogenesis. When associated with human disease aetiology, the eosinophil takes on a pathogenic rather than a protective role. This maladaptive response, called “eosinophilic immune dysfunction” herein, appears central to exacerbation pathogenesis and disease control in severe asthma and may be involved in the aetiology of other eosinophil-related conditions ranging from organ-system-limited diseases such as phenotypic subsets of chronic obstructive pulmonary disease and chronic rhinosinusitis with nasal polyposis to more broadly systemic diseases such as eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. In this review, we describe the evidence supporting eosinophilic functions related to health and homeostasis and explore the contribution of eosinophilic immune dysfunction to human disease.

          Abstract

          The current era of therapies that specifically target eosinophils has yielded new insights into the functional significance of eosinophils in the maintenance of health and the effects of eosinophilic immune dysfunction on disease pathogenesis. https://bit.ly/3pVPLR5

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          Most cited references99

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          2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides.

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            Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial

            Benralizumab is a humanised, afucosylated, anti-interleukin-5 receptor α monoclonal antibody that induces direct, rapid, and nearly complete depletion of eosinophils. We aimed to assess the efficacy and safety of benralizumab as add-on therapy for patients with severe, uncontrolled asthma and elevated blood eosinophil counts.
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              Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial

              Eosinophilia is associated with worsening asthma severity and decreased lung function, with increased exacerbation frequency. We assessed the safety and efficacy of benralizumab, a monoclonal antibody against interleukin-5 receptor α that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity, for patients with severe, uncontrolled asthma with eosinophilia.
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                Author and article information

                Journal
                Eur Respir Rev
                Eur Respir Rev
                ERR
                errev
                European Respiratory Review
                European Respiratory Society
                0905-9180
                1600-0617
                31 March 2022
                26 January 2022
                : 31
                : 163
                : 210150
                Affiliations
                [1 ]Guy's Severe Asthma Centre, Guy's & St Thomas’ NHS Trust, London, UK
                [2 ]School of Immunology & Microbial Sciences, King's College London, London, UK
                [3 ]Division of Pulmonary, Critical Care, and Sleep Medicine, Dept of Medicine, University of California, San Diego, La Jolla, CA, USA
                [4 ]Médecine Interne, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
                Author notes
                Corresponding author: David Jackson ( david.jackson@ 123456gstt.nhs.uk )
                Article
                ERR-0150-2021
                10.1183/16000617.0150-2021
                9489126
                35082127
                1df62ff4-6d9c-4289-b486-d21cd8fe80d6
                Copyright ©The authors 2022

                This version is distributed under the terms of the Creative Commons Attribution Licence 4.0.

                History
                : 30 June 2021
                : 22 October 2021
                Funding
                Funded by: AstraZeneca, doi 10.13039/100004325;
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