Comparable actions of omalizumab on mast cells and basophils

Serrano‐Candelas, Eva; Martín, Margarita; Valero, Antonio; Bartra, Joan; Gastaminza, Gabriel; Goikoetxea, M. J.; Martı́n, Margarita; Ferrer, Marta

doi:10.1111/cea.12668

Cited by 64 publications

(53 citation statements)

References 43 publications

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“…This observation was confirmed by Serrano-Candelas et al [25] on mast cells. They also proved that this phenomenon is associated with IgE-dependent decreased signalling from FceRI, connected with inhibition of proximal phosphorylation in the Syk-LAT-PLCg axis, as well as inhibition of degranulation and synthesis of leukotrienes.…”

Section: Pharmacodynamic Properties Of Omalizumabsupporting

confidence: 73%

The Effect of Omalizumab on Eosinophilic Inflammation of the Respiratory Tract in Patients with Allergic Asthma

Kupryś‐Lipińska¹,

Molińska²,

Kuna³

2016

Advances in Respiratory Medicine

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Bronchial asthma is characterised by high levels of immunoglobulin E (IgE) and overproduction of pro-inflammatory cytokines, including interleukins IL-4, IL-13 and IL-5 needed for, amongst other things, the production of IgE and the differentiation, maturation, migration and survival of eosinophils. Eosinophils are one of the most important cells in allergic inflammation. Their presence in tissue is linked to the persistence of inflammatory infiltrate, tissue damage and remodelling. Although these cells are very sensitive to corticosteroids, some asthmatic patients do not respond to high doses of these drugs, even when administered systemically. Transbronchial biopsies and bronchoalveolar lavage performed in patients with steroid-resistant asthma have demonstrated higher levels of eosinophils and Th2-type cytokines (IL-4 and IL-5) compared to steroid-sensitive patients. Clinical studies have confirmed that the very effective treatment in these cases is therapy with omalizumab -an anti-IgE monoclonal antibody. The paper discusses the efficacy of omalizumab in reducing eosinophil number in peripheral blood and in the airways of asthmatic patients based on basic, clinical, observational studies and case reports. The significance of omalizumab therapy in asthma control and mechanisms that regulate the effects of omalizumab on eosinophils are evaluated.

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Section: Pharmacodynamic Properties Of Omalizumabsupporting

confidence: 73%

The Effect of Omalizumab on Eosinophilic Inflammation of the Respiratory Tract in Patients with Allergic Asthma

Kupryś‐Lipińska¹,

Molińska²,

Kuna³

2016

Advances in Respiratory Medicine

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“…Interestingly, in recent years, the drug's action has been shown to go further, dissociating bound IgE from the IgE-Fc ε RI complex (mechanism (2) in Figure 3) [46, 47]. Thus, at a physiological concentration range, OmAb may accelerate the dissociation of the preformed IgE-Fc ε RI complex on the surfaces of mast cells and basophils in addition to its ability to neutralize the free IgE, leading to an impairment of the IgE-inflammatory signaling cascade [47]. Moreover, the density of Fc ε RI expression on basophils, mast cells, and dendritic cells falls notably in patients receiving anti-IgE treatment within the first week of OmAb application [8].…”

Section: Anti-ige-based Treatmentsmentioning

confidence: 99%

“…These findings suggested another mechanism of action for OmAb, apart from its ability to sequester free IgE. Lowering free IgE levels may downregulate the levels of IgE receptor expression density on the surface of mast cells in the long term, but this would not appear to be responsible for the rapid improvement reported in the clinical symptoms; a more likely reason is OmAb's ability to dissociate prebound IgE from Fc Ɛ RI [46, 47]. Nevertheless, it is still unclear how OmAb works in CSU: in addition, the fact that OmAb is not effective in all patients suggests the involvement of mechanisms/pathways in CSU other than the IgE cascade.…”

Section: Anti-ige-based Treatmentsmentioning

confidence: 99%

IgE-Related Chronic Diseases and Anti-IgE-Based Treatments

Navinés-Ferrer

Serrano‐Candelas

Molina-Molina

et al. 2016

Journal of Immunology Research

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IgE is an immunoglobulin that plays a central role in acute allergic reactions and chronic inflammatory allergic diseases. The development of a drug able to neutralize this antibody represents a breakthrough in the treatment of inflammatory pathologies with a probable allergic basis. This review focuses on IgE-related chronic diseases, such as allergic asthma and chronic urticaria (CU), and on the role of the anti-IgE monoclonal antibody, omalizumab, in their treatment. We also assess the off-label use of omalizumab for other pathologies associated with IgE and report the latest findings concerning this drug and other new related drugs. To date, omalizumab has only been approved for severe allergic asthma and unresponsive chronic urticaria treatments. In allergic asthma, omalizumab has demonstrated its efficacy in reducing the dose of inhaled corticosteroids required by patients, decreasing the number of asthma exacerbations, and limiting the effect on airway remodeling. In CU, omalizumab treatment rapidly improves symptoms and in some cases achieves complete disease remission. In systemic mastocytosis, omalizumab also improves symptoms and its prophylactic use to prevent anaphylactic reactions has also been discussed. In other pathologies such as atopic dermatitis, food allergy, allergic rhinitis, nasal polyposis, and keratoconjunctivitis, omalizumab significantly improves clinical manifestations. Omalizumab acts in two ways: by sequestering free IgE and by accelerating the dissociation of the IgE-Fcε receptor I complex.

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“…Food allergens likewise induce a shift toward Th2 immunity and sensitize the MCs by binding to their FcεRI receptors[52]. Monomeric IgE can enhance MC activity and mediator release[53]. Sensitization of MCs with monoclonal IgE stimulates up-regulation of genes encoding the inflammatory cytokines, chemokines, cytokine and chemokine receptors, adhesion molecules, anti-apoptosis proteins and cytoskeletal elements[52].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, it has been shown that a human monoclonal IgE can stimulate MCs to produce histamine-releasing factor[54]. Omalizumab, itself, has been shown to sequester monomeric IgE, thereby reducing its priming effect on MCs[53]. …”

Section: Introductionmentioning

confidence: 99%

Possible therapeutic role of IgE blockade in irritable bowel syndrome

Magen

Chikovani

2016

WJG

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Omalizumab is a humanized monoclonal antibody that binds to the high-affinity type-I IgE Fc receptors on mast cells (MCs) and basophils, inhibiting the IgE immune pathway. Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder, and dysregulation of the immune system likely contributes to its etiology and/or symptomatology. Colonic biopsies from patients with IBS demonstrate considerable increase in the number of degranulating MCs releasing histamine in proximity to nerves, and this event may underlie the common IBS symptom of abdominal pain. Pharmacologic control of MC activation and mediator release is a current area of active interest in the field of IBS research. Recently, we and Pearson et al described 2 cases of patients with IBS with diarrhea (IBS-D) showing positive clinical response to omalizumab. In both cases, the female patients had severe, long-lasting IBS-D and achieved an almost complete resolution of IBS symptoms. Both patients were also able to discontinue all IBS medications after commencing the anti-IgE therapy. For both patients, the omalizumab treatment showed a relatively rapid onset of action, resembling the efficacy observed in and previously reported for patients with chronic spontaneous urticaria. In this Editorial, we discuss the possible biological mechanisms that may underlie the clinical efficacy of omalizumab in IBS. We suggest that there is a need for a well-designed prospective study to investigate the therapeutic effects of anti-IgE in IBS.

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Comparable actions of omalizumab on mast cells and basophils

Abstract: Our data prove the existence of common mechanisms of action of OmAb in mast cells and basophils that would explain its effectiveness and rapid effect in chronic urticaria and provide a basis for its use in other diseases mediated by these cells.

Cited by 64 publications

References 43 publications

The Effect of Omalizumab on Eosinophilic Inflammation of the Respiratory Tract in Patients with Allergic Asthma

The Effect of Omalizumab on Eosinophilic Inflammation of the Respiratory Tract in Patients with Allergic Asthma

IgE-Related Chronic Diseases and Anti-IgE-Based Treatments

Possible therapeutic role of IgE blockade in irritable bowel syndrome

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