Anti-IgE therapy for IgE-mediated allergic diseases: from neutralizing IgE antibodies to eliminating IgE+ B cells

Hu, Jiayun; Chen, Jiajie; Ye, Lanlan; Cai, Zelang; J, Sun; Ji, Kunmei

doi:10.1186/s13601-018-0213-z

Cited by 46 publications

(33 citation statements)

References 71 publications

(84 reference statements)

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“…Upon activation, mast cells produce cytoplasmic granules with pro‐inflammatory and allergic mediators that are released into the surrounding environment (Hu et al, 2018). Stimulation‐induced wrinkling of the cell membrane facilitates the release of particles into the surrounding environment (Ohsawa & Hirasawa, 2012).…”

Section: Introductionmentioning

confidence: 99%

Aurora kinase inhibitor tozasertib suppresses mast cell activation in vitro and in vivo

Zhang

Sun

et al. 2020

British J Pharmacology

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Background and Purpose: Mast cells are important in allergic reactions. Here, we assessed the anti-allergic effects of the anti-cancer drug tozasertib specifically regarding regulatory effects on mast cell activation. Experimental Approach: Tozasertib effects on mast cell degranulation were determined by measuring β-hexosaminidase and histamine release and by assessing morphological changes in RBL-2H3 and mouse bone marrow-derived mast cells (BMMCs) stimulated with mouse anti-dinitrophenyl (DNP)-IgE/DNP-human serum albumin or human LAD2 cells activated with phorbol-12-myristate 13-acetate plus calcium ionophore (PMACI). Western blots were performed to detect the expression of molecules involved in NF-κB, MAPK, and Aurora kinase signalling. in vivo antiallergic effects of tozasertib were determined in the murine IgE-mediated passive cutaneous anaphylaxis (PCA) and ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) models. Key Results: Tozasertib treatment decreased high-affinity IgE receptor (FcεRI) or PMACI-mediated degranulation in RBL-2H3 cells and in BMMCs or LAD2 cells as shown by β-hexosaminidase or histamine levels. Similarly, tozasertib prevented morphological changes in mast cells, such as particle release and F-actin reorganization. In addition, tozasertib markedly decreased expression of phosphorylated (p)-NF-κB p65, p-Erk1/2, p-p38, and p-Aurora A/B, indicating that tozasertib can inhibit the signalling pathway mediating mast cell activation. Tozasertib attenuated IgE/Ag-induced PCA dose-dependently, as shown by reduced Evans blue staining. Similarly, tozasertib reduced body temperature levels and serum histamine levels in OVAchallenged ASA mice. Conclusion and Implications:The Aurora kinase inhibitor tozasertib suppressed mast cell activation in vitro and in vivo. Tozasertib may be a potential drug, targeting mast cell activation, to treat allergic diseases or mastocytosis.

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Section: Introductionmentioning

confidence: 99%

Aurora kinase inhibitor tozasertib suppresses mast cell activation in vitro and in vivo

Zhang

Sun

et al. 2020

British J Pharmacology

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“…Because of its key role in type I hypersensitivity reactions, IgE has always been a prime target for intervention in allergic disease. This has been approached from two different angles: (a) targeting soluble IgE and (b) targeting B cells that express surface IgE (119). Another less specific approach for targeting IgE production has been the depletion of all B cells using the anti-CD20 antibody rituximab (Figure 3).…”

Section: Targeting Ige and Ige-expressing B Cellsmentioning

confidence: 99%

The use of biologics for immune modulation in allergic disease

Veen¹,

Akdiş²

2019

Journal of Clinical Investigation

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“…Novel research on IgE-targeted therapies has been recently reviewed focusing on serum IgE neutralization, inhibiting IgE receptors in effector cells, and targeting IgE + plasma cells. 101 Baseline blood eosinophil levels can be used as prognostic markers for response to omalizumab in patients with allergic asthma. 102 A higher eosinophil count corresponded to a more effective omalizumab response as observed from an increased rate of reduction in asthma exacerbations.…”

Section: A S Thma Tre Atmentmentioning

confidence: 99%

Highlights and recent developments in airway diseases in EAACI journals (2018)

Bousquet

Akdiş

Grattan

et al. 2019

Allergy

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The European Academy of Allergy and Clinical Immunology (EAACI) supports three journals: Allergy, Pediatric Allergy and Immunology, and Clinical and Translational Allergy. EAACI's major goals include supporting the promotion of health, in which the prevention of allergy and asthma plays a critical role, and disseminating the knowledge of allergic disease to all stakeholders. In 2018, the remarkable progress in the identification of basic mechanisms of allergic and respiratory diseases as well as the translation of these findings into clinical practice were observed. Last year's highlights include publication of EAACI guidelines for allergen immunotherapy, many EAACI Position Papers covering important aspects for the specialty, better understanding of molecular and cellular mechanisms, identification of biomarkers for disease prediction and progress monitoring, novel prevention and intervention studies, elucidation of mechanisms of multimorbidities, introduction of new drugs to the clinics, recently completed phase three clinical studies, and publication of a large number of allergen immunotherapy studies and meta‐analyses.

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Anti-IgE therapy for IgE-mediated allergic diseases: from neutralizing IgE antibodies to eliminating IgE+ B cells

Cited by 46 publications

References 71 publications

Aurora kinase inhibitor tozasertib suppresses mast cell activation in vitro and in vivo

Aurora kinase inhibitor tozasertib suppresses mast cell activation in vitro and in vivo

The use of biologics for immune modulation in allergic disease

Highlights and recent developments in airway diseases in EAACI journals (2018)

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