Evolution of our view on the IgE molecule role in bronchial asthma and the clinical effect of its modulation by omalizumab: Where do we stand today?

Novosad, Jakub; Krčmová, Irena

doi:10.1177/2058738420942386

Cited by 11 publications

(9 citation statements)

References 96 publications

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“…Together with IL-13, IL-4 provides the so-called “first signal” that induces IgE production by B cells ( Geha et al, 2003 ; Froidure et al, 2016 ). IgE class switching also requires a “second signal” for maturation of B lymphocytes, expressed by the B-T cell cognate interaction consisting of an immunological synapse engaging both T cell receptor (TCR) and CD40/CD40 ligand (CD40L) coupling ( Novosad and Krčmová, 2020 ). Although Th2 and Tfh cells are probably the most relevant cellular sources of IL-4 and IL-13, these cytokines are also synthesized by ILC2, which thus contribute to stimulate IgE production ( Maggi et al, 2017 ).…”

Section: Pathobiologic Roles Of Il-4 and Il-13 In Type 2 Asthmamentioning

confidence: 99%

Interleukins 4 and 13 in Asthma: Key Pathophysiologic Cytokines and Druggable Molecular Targets

et al. 2022

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Interleukins (IL)-4 and -13 play a pivotal role in the pathobiology of type-2 asthma. Indeed, IL-4 is crucially involved in Th2 cell differentiation, immunoglobulin (Ig) class switching and eosinophil trafficking. IL-13 cooperates with IL-4 in promoting IgE synthesis, and also induces nitric oxide (NO) production, goblet cell metaplasia and fibroblast proliferation, as well as elicits contractile responses and hyperplasia of airway smooth muscle cells.IL-4 and IL-13 share common signaling pathways, activated by the binding of both cytokines to receptor complexes including the α-subunit of the IL-4 receptor (IL-4Rα). Therefore, the subsequent receptor dimerization is responsible for the pathophysiologic effects of IL-4 and IL-13. By selectively blocking IL-4Rα, the fully human IgG4 monoclonal antibody dupilumab behaves as a dual receptor antagonist of both IL-4 and IL-13. Through this mechanism of action, dupilumab exerts effective therapeutic actions in type-2 inflammation, thus decreasing asthma exacerbations, FeNO (fractional exhaled NO) levels, and the intake of oral corticosteroids (OCS). In addition to being approved for the add-on biological therapy of severe asthma, dupilumab has also been licensed for the treatment of nasal polyposis and atopic dermatitis.

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Section: Pathobiologic Roles Of Il-4 and Il-13 In Type 2 Asthmamentioning

confidence: 99%

Interleukins 4 and 13 in Asthma: Key Pathophysiologic Cytokines and Druggable Molecular Targets

et al. 2022

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“…Acting together with IL-13, IL-4 represents the 'first signal' which stimulates IgE production by B lymphocytes [37,38]. Isotype switching leading to Ig rearrangement at the level of B lymphocytes also depends on a 'second signal' consisting of the so-called B-T cell cognate relationship expressed by an immunological synapse involving both antigen/T cell receptor (TCR) and CD40/CD40 ligand (CD40 L) interactions [39]. Though Th2 and Tfh lymphocytes are the main sources of IL-4 and IL-13, such cytokines can be also secreted by ILC2 [30].…”

Section: Pathophysiologic Functions Of Il-4 and Il-13 In Type 2 Asthmamentioning

confidence: 99%

Biological Therapy of Severe Asthma with Dupilumab, a Dual Receptor Antagonist of Interleukins 4 and 13

Pelaia

Crimi

et al. 2022

Vaccines

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Interleukin-4 (IL-4) and interleukin-13 (IL-13) are key cytokines involved in the pathophysiology of both immune-inflammatory and structural changes underlying type 2 asthma. IL-4 plays a pivotal role in Th2 cell polarization, immunoglobulin E (IgE) synthesis and eosinophil recruitment into the airways. IL-13 synergizes with IL-4 in inducing IgE production and also promotes nitric oxide (NO) synthesis, eosinophil chemotaxis, bronchial hyperresponsiveness and mucus secretion, as well as the proliferation of airway resident cells such as fibroblasts and smooth muscle cells. The biological effects of IL-4 and IL-13 are mediated by complex signaling mechanisms activated by receptor dimerization triggered by cytokine binding to the α-subunit of the IL-4 receptor (IL-4Rα). The fully human IgG4 monoclonal antibody dupilumab binds to IL-4Rα, thereby preventing its interactions with both IL-4 and IL-13. This mechanism of action makes it possible for dupilumab to effectively inhibit type 2 inflammation, thus significantly reducing the exacerbation of severe asthma, the consumption of oral corticosteroids (OCS) and the levels of fractional exhaled NO (FeNO). Dupilumab has been approved not only for the add-on therapy of severe asthma, but also for the biological treatment of atopic dermatitis and nasal polyposis.

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“…Omalizumab was the first biological therapy developed for asthma, and it has now been used for 15 years. During these years, the functions of IgE in bronchial asthma have proven to be more complex than that of the classical role in allergy and anaphylaxis (reviewed in [ 89 ]). For example, smooth muscle cells in lung tissue have receptors for IgE, and it is involved in their proliferation, independent of the presence of allergens.…”

Section: Monoclonal Antibodies and Treatment Of Airway Diseasesmentioning

confidence: 99%

“…For example, smooth muscle cells in lung tissue have receptors for IgE, and it is involved in their proliferation, independent of the presence of allergens. IgE also plays a role in non-allergic diseases such as chronic idiopathic urticaria and CRSwNP and is involved in eosinophilic inflammation [ 89 ].…”

Section: Monoclonal Antibodies and Treatment Of Airway Diseasesmentioning

confidence: 99%

Monoclonal Antibodies and Airway Diseases

Lyly

Laulajainen‐Hongisto

Gevaert

et al. 2020

IJMS

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Monoclonal antibodies, biologics, are a relatively new treatment option for severe chronic airway diseases, asthma, allergic rhinitis, and chronic rhinosinusitis (CRS). In this review, we focus on the physiological and pathomechanisms of monoclonal antibodies, and we present recent study results regarding their use as a therapeutic option against severe airway diseases. Airway mucosa acts as a relative barrier, modulating antigenic stimulation and responding to environmental pathogen exposure with a specific, self-limited response. In severe asthma and/or CRS, genome–environmental interactions lead to dysbiosis, aggravated inflammation, and disease. In healthy conditions, single or combined type 1, 2, and 3 immunological response pathways are invoked, generating cytokine, chemokine, innate cellular and T helper (Th) responses to eliminate viruses, helminths, and extracellular bacteria/fungi, correspondingly. Although the pathomechanisms are not fully known, the majority of severe airway diseases are related to type 2 high inflammation. Type 2 cytokines interleukins (IL) 4, 5, and 13, are orchestrated by innate lymphoid cell (ILC) and Th subsets leading to eosinophilia, immunoglobulin E (IgE) responses, and permanently impaired airway damage. Monoclonal antibodies can bind or block key parts of these inflammatory pathways, resulting in less inflammation and improved disease control.

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Evolution of our view on the IgE molecule role in bronchial asthma and the clinical effect of its modulation by omalizumab: Where do we stand today?

Cited by 11 publications

References 96 publications

Interleukins 4 and 13 in Asthma: Key Pathophysiologic Cytokines and Druggable Molecular Targets

Interleukins 4 and 13 in Asthma: Key Pathophysiologic Cytokines and Druggable Molecular Targets

Biological Therapy of Severe Asthma with Dupilumab, a Dual Receptor Antagonist of Interleukins 4 and 13

Monoclonal Antibodies and Airway Diseases

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