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Omalizumab and degranulation

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https://www.readbyqxmd.com/read/27694038/targeting-mast-cells-uncovering-prolific-therapeutic-role-in-myriad-diseases
#1
Jatinder Singh, Ramanpreet Shah, Dhandeep Singh
The mast cells are integral part of immune system and they have pleiotropic physiological functions in our body. Any type of abnormal stimuli causes the mast cells receptors to spur the otherwise innocuous mast cells to degranulate and release inflammatory mediators like histamine, cytokines, chemokines and prostaglandins. These mediators are involved in various diseases like allergy, asthma, mastocytosis, cardiovascular disorders, etc. Herein, we describe the receptors involved in degranulation of mast cells and are broadly divided into four categories: G-protein coupled receptors, ligand gated ion channels, immunoreceptors and pattern recognition receptors...
September 29, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27358151/efficacy-and-safety-of-omalizumab-in-paediatric-age-an-update-of-literature-data
#2
N Matin, O Tabatabaie, R Falsaperla, P Pavone, A Serra, S Cocuzza, P Di Mauro, L Licciardello, R Lubrano, G Vitaliti
Immunoglobulin E (IgE) was discovered in 1966 and was found responsible for immune defense against helminths, type I hypersensitivity and allergic diseases. IgE mediates allergic responses by binding to Fc receptors (the high affinity Fc-epsilon receptor I and the low affinity Fc-epsilon receptor II or CD23) expressed on tissue mast cells and blood basophils. This binding leads to degranulation and release of pro-inflammatory mediators. Considering the pivotal role of IgE in allergic diseases, antibodies against IgE potentiate an array of new therapeutic strategies and in this regard omalizumab (rhuMAb-E25, Xolair) has been developed as a monoclonal biologic drug to block serum IgEs...
April 2016: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/27264000/role-of-ige-in-autoimmunity
#3
Miguel A Sanjuan, Divya Sagar, Roland Kolbeck
There is accumulating evidence to suggest that IgE plays a significant role in autoimmunity. The presence of circulating self-reactive IgE in patients with autoimmune disorders has been long known but, at the same time, largely understudied. However, studies have shown that the increased IgE concentration is not associated with higher prevalence for atopy and allergy in patients with autoimmune diseases, such as systemic lupus erythematosus. IgE-mediated mechanisms are conventionally known to facilitate degranulation of mast cells and basophils and promote TH2 immunity, mechanisms that are not only central to mounting an appropriate defense against parasitic worms, noxious substances, toxins, venoms, and environmental irritants but that also trigger exuberant allergic reactions in patients with allergies...
June 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/26955580/position-statement-for-the-use-of-omalizumab-in-the-management-of-chronic-spontaneous-urticaria-in-indian-patients
#4
REVIEW
Kiran Godse, Murlidhar Rajagopalan, Mukesh Girdhar, Sanjiv Kandhari, Bela Shah, Prashant N Chhajed, Sushil Tahiliani, D S Krupa Shankar, Vijay Somani, Vijay Zawar
Chronic spontaneous urticaria (CSU) affects 1% of the world population and also their quality of life, and 50% of these patients are refractory to H1-antihistamines. Omalizumab is a humanized monoclonal anti-IgE antibody that binds with free IgE antibodies and reduces the circulating levels of free IgE. This reduction in free IgE prevents mast-cell degranulation. The EAACI/GA2LEN/EDF/WAO guidelines recommend omalizumab as the third-line of therapy as an add-on to antihistamines. The recommended dose of omalizumab is 300 mg, 4 weekly in the management of CSU refractory to standard of care with H1-antihistamines in adults and adolescents ≥12 years of age...
January 2016: Indian Dermatology Online Journal
https://www.readbyqxmd.com/read/26509363/comparable-actions-of-omalizumab-on-mast-cells-and-basophils
#5
E Serrano-Candelas, R Martinez-Aranguren, A Valero, J Bartra, G Gastaminza, M J Goikoetxea, M Martín, M Ferrer
BACKGROUND: Omalizumab (OmAb) has recently been approved for the treatment of diseases other than allergic asthma, including chronic urticaria. The exploration of the use of OmAb in chronic urticaria was based on the presence of IgE autoantibodies against autoantigens such as anti-IgE, anti-FcεRI, and IgE antibodies against thyroid peroxidase in certain patients with chronic urticaria. OmAb recognizes and sequesters free IgE to prevent its interaction with FcεRI. However, OmAb is equally and rapidly effective against autoimmune and non-autoimmune urticaria, suggesting the possible involvement of additional mechanisms of IgE...
January 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/25291953/omalizumab-anti-ige-therapy-increases-blood-glucose-levels-in-severe-persistent-allergic-asthma-patients-with-diabetes-mellitus-18-month-follow-up
#6
Arzu Didem Yalcin, Reginald M Gorczynski, Aykut Cilli, Ludwig Strauss
BACKGROUND: Therapeutic anti-IgE antibodies (Xolair, omalizumab) able to reduce free IgE levels and to block the binding of IgE to Fcepsilon RI without cross-linking IgE and triggering degranulation of IgE-sensitised cells have been developed. METHODS: We had two male patients of severe persistent allergic asthma with type-2 diabetes mellitus at the ages of 57 and 52 and who had suffered a side-effect of increased blood glucose level that caused a need for an extra insulin injection to control the hyperglycemia...
2014: Clinical Laboratory
https://www.readbyqxmd.com/read/25257818/omalizumab-may-not-inhibit-mast-cell-and-basophil-activation-in-vitro
#7
REVIEW
J Gericke, T Ohanyan, M K Church, M Maurer, M Metz
BACKGROUND: In March 2014, omalizumab, a monoclonal anti-IgE antibody, was approved for the treatment of chronic spontaneous urticaria (CSU). The primary mode of action of omalizumab is considered to be the reduction in free IgE serum levels and the subsequent down-regulation of FcεRI, the high affinity receptor for IgE, on mast cells and basophils. Recently, it has been suggested that most CSU patients have an autoimmune aetiology which may lead to chronic activation of mast cells and basophils...
September 2015: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/25217402/omalizumab-a-review-of-its-use-in-patients-with-chronic-spontaneous-urticaria
#8
REVIEW
Paul L McCormack
Omalizumab (Xolair(®)) is a humanized, recombinant, IgG, anti-IgE monoclonal antibody that binds to the Fc region of free IgE and prevents it from binding to its high-affinity receptor (FcεR1) on mast cells and basophils. This reduction in free IgE leads to a reduction in mast cell/basophil degranulation and the release of histamine, and to the down-regulation of FcεR1 receptors on these cells. Omalizumab does not bind to cell-bound IgE or to IgG. In well-controlled clinical trials in patients with chronic spontaneous urticaria and persistent symptoms despite background treatment with antihistamines, add-on therapy with subcutaneous omalizumab 300 mg every 4 weeks for 12 or 24 weeks significantly reduced the severity of itching, and the number and size of hives, and increased patients' health-related quality of life and the proportion of days free from angioedema compared with placebo...
September 2014: Drugs
https://www.readbyqxmd.com/read/24950847/omalizumab-effectively-prevents-recurrent-refractory-anaphylaxis-in-a-patient-with-monoclonal-mast-cell-activation-syndrome
#9
Amanda Jagdis, Peter Vadas
No abstract text is available yet for this article.
July 2014: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/24948369/the-potential-pharmacologic-mechanisms-of-omalizumab-in-patients-with-chronic-spontaneous-urticaria
#10
REVIEW
Tse Wen Chang, Christina Chen, Chien-Jen Lin, Martin Metz, Martin K Church, Marcus Maurer
In patients given a diagnosis of chronic spontaneous urticaria (CSU), there are no obvious external triggers, and the factors that initiate the clinical symptoms of wheal, flare, and itch arise from within the patient. Most patients with CSU have an autoimmune cause: some patients produce IgE autoantibodies against autoantigens, such as thyroperoxidase or double-stranded DNA, whereas other patients make IgG autoantibodies against FcεRI, IgE, or both, which might chronically activate mast cells and basophils...
February 2015: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/24845463/unraveling-the-significance-of-ige-autoantibodies-in-organ-specific-autoimmunity-lessons-learned-from-bullous-pemphigoid
#11
REVIEW
K A N Messingham, H M Holahan, J A Fairley
Bullous pemphigoid (BP), a cutaneous autoimmune blistering disease, has provided a useful model to elucidate a role for IgE in autoimmunity. IgE antibodies specific for the BP180 autoantigen are detected in sera and biopsy samples from the majority of BP patients. In BP biopsies, both IgE and BP180 antigen localize to the surface of mast cells, and incubation of circulating basophils from these patients with BP180 protein triggered degranulation. The in vivo pathogenicity of BP180-specific IgE was confirmed in mouse models, where injection of purified BP IgE into human skin grafted onto nu/nu mice replicated the early phase of lesion development, including mast cell degranulation, eosinophil infiltration and development of urticarial plaques...
August 2014: Immunologic Research
https://www.readbyqxmd.com/read/24589165/a-critical-appraisal-of-omalizumab-as-a-therapeutic-option-for-chronic-refractory-urticaria-angioedema
#12
David M Lang
No abstract text is available yet for this article.
April 2014: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/23258953/cc-chemokine-ccl15-expression-and-possible-implications-for-the-pathogenesis-of-ige-related-severe-asthma
#13
REVIEW
Yasuo Shimizu, Kunio Dobashi
Airway inflammation is accompanied by infiltration of inflammatory cells and an abnormal response of airway smooth muscle. These cells secrete chemokines and express the cell surface chemokine receptors that play an important role in the migration and degranulation of inflammatory cells. Omalizumab is a monoclonal antibody directed against immunoglobulin E, and its blocking of IgE signaling not only reduces inflammatory cell infiltration mediated by the Th2 immune response but also inhibits other immune responses...
2012: Mediators of Inflammation
https://www.readbyqxmd.com/read/22374203/omalizumab-inhibits-acceleration-of-fc%C3%AE%C2%B5ri-mediated-responsiveness-of-immature-human-mast-cells-by-immunoglobulin-e
#14
Yoshimichi Okayama, Jun-ichi Kashiwakura, Tomomi Sasaki-Sakamoto, Kenji Matsumoto, Noriko Hashimoto, Kazumitsu Ohmori, Toshiaki Kawakami, Hirohisa Saito, Chisei Ra
BACKGROUND: A large body of evidence has demonstrated that treatment with omalizumab is clinically effective for the management of moderate to severe allergic asthma, emphasizing the importance of IgE in the pathogenesis of allergic asthma. We hypothesized that IgE accelerates FcεRI-mediated responsiveness of "immature" human mast cells (MCs) and that omalizumab downregulates the acceleration. OBJECTIVES: To examine when MC progenitors acquired the ability to degranulate following FcεRI aggregation, whether IgE accelerates the responsiveness of immature MCs following FcεRI aggregation, and whether omalizumab regulates such an acceleration...
March 2012: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/22264640/omalizumab-beyond-asthma
#15
REVIEW
J Sanchez, R Ramirez, S Diez, S Sus, A Echenique, M Olivares, R Cardona
INTRODUCTION: Omalizumab has been demonstrated to be a successful therapy in the management of asthma through reduction of patient's symptoms and use of inhaled corticosteroids. The effect of omalizumab is achieved by immunoglobulin E (IgE) blockage and other secondary mechanisms resulting from this blockage. Because other diseases have an important IgE mediation in their physiopathology, the question arises as to if omalizumab would be useful in the treatment of other IgE-mediated diseases...
September 2012: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/22226669/an-anti-ige-monoclonal-antibody-that-binds-to-ige-on-cd23-but-not-on-high-affinity-ige-fc-receptors
#16
Yu-Yu Shiung, Chen-Yi Chiang, Jiun-Bo Chen, Pheidias C Wu, Alfur Fu-Hsin Hung, Donic Chien-Sheng Lu, Rong-Long Pan, Tse Wen Chang
A new monoclonal antibody (mAb), specific for human IgE, the central mediator of immediate-type hypersensitivity reactions, has been shown to possess a unique set of binding specificities. The mAb, 8D6, binds to a conformational epitope on the CH3 domain of human e immunoglobulin and can compete with omalizumab for binding to IgE. Like omalizumab, it does not bind to IgE bound by the high-affinity IgE.Fc receptor (FcɛRI) on basophils and mast cells. It also does not cause activation and degranulation of IgE-pulsed, human FcɛRI-expressing rat basophilic leukemic cells (RBL SX-38)...
July 2012: Immunobiology
https://www.readbyqxmd.com/read/22092741/failure-of-omalizumab-xolair%C3%A2-in-the-treatment-of-a-case-of-solar-urticaria-caused-by-ultraviolet-a-and-visible-light
#17
Giacomo Duchini, Wolfgang Bäumler, Andreas J Bircher, Kathrin Scherer
Solar urticaria is a rare photodermatosis probably caused by a chromophore, that - if activated by light of a specific spectrum - binds to mast cell-bound IgE and elicits degranulation. In our patient an action spectrum in ultraviolet A and visible light range was found, in the autologous serum test the presence of a serum chromophore for the same action spectra could be demonstrated, which may underline this pathogenetic hypothesis. Symptoms did not improve using antihistamines and sun protection. Photo hardening was denied from the patient, immunosuppression and plasmapheresis were discussed but not considered...
December 2011: Photodermatology, Photoimmunology & Photomedicine
https://www.readbyqxmd.com/read/21659864/insect-anaphylaxis-addressing-clinical-challenges
#18
REVIEW
James M Tracy, Elena J Lewis, Jeffrey G Demain
PURPOSE OF REVIEW: Few allergic reactions are as potentially life-threatening, or frightening to the patient, as anaphylaxis. Food, medications, and insect stings are the three most common triggers of anaphylaxis, but insect allergy provides the best opportunity to understand the biology of anaphylaxis. If the physician can establish a diagnosis of insect allergy, treatment with nearly 98% effectiveness can be initiated. However, sometimes patients have a compelling history of insect sting anaphylaxis, but negative skin and blood tests...
August 2011: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/21272035/inhibition-of-ongoing-allergic-reactions-using-a-novel-anti-ige-darpin-fc-fusion-protein
#19
A Eggel, P Buschor, M J Baumann, P Amstutz, B M Stadler, M Vogel
BACKGROUND: Aggregation of the high-affinity IgE receptor (FcεRI) with the low-affinity IgG receptor (FcγRIIb) on basophils or mast cells has been shown to inhibit allergen-induced cell degranulation. Molecules cross-linking these two receptors might therefore be of interest for the treatment of allergic disorders. Here, we demonstrate the generation of a novel bispecific fusion protein efficiently aggregating FcεRI-bound IgE with FcγRIIb on the surface of basophils to prevent pro-inflammatory mediator release...
July 2011: Allergy
https://www.readbyqxmd.com/read/19414793/ige-fcepsilonri-interactions-determine-hiv-coreceptor-usage-and-susceptibility-to-infection-during-ontogeny-of-mast-cells
#20
J Bruce Sundstrom, Gregory A Hair, Aftab A Ansari, W Evan Secor, Alasdair M Gilfillan, Dean D Metcalfe, Arnold S Kirshenbaum
Progenitor mast cells (prMCs), derived from CD34(+) precursors are CD4(+)/CCR5(+)/CXCR4(+) and susceptible to CCR5(R5)-tropic virus but only marginally susceptible to CXCR4(X4)-tropic HIV. As infected prMCs mature within extravascular compartments, they become both latently infected and HIV-infection resistant, and thus capable of establishing an inducible reservoir of CCR5-tropic infectious clones. In this report we provide the first evidence that IgE-FcepsilonRI interactions, occurring during a unique period of mast cell (MC) ontogeny, enhance prMC susceptibility to X4 and R5X4 virus...
May 15, 2009: Journal of Immunology: Official Journal of the American Association of Immunologists
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