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https://www.readbyqxmd.com/read/27856823/mepolizumab-in-the-management-of-severe-eosinophilic-asthma-in-adults-current-evidence-and-practical-experience
#1
REVIEW
Gilda Varricchi, Diego Bagnasco, Matteo Ferrando, Francesca Puggioni, Giovanni Passalacqua, Giorgio W Canonica
Eosinophils represent approximately 1% of peripheral blood leukocytes in normal donors and their maturation and differentiation in the bone marrow are mainly regulated by interleukin (IL)-5 [Broughton et al. 2015]. IL-5, a cytokine that belongs to the β common-chain family, together with IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF), stimulates also the activation and survival of eosinophils and, to some extent, of basophils. IL-5 binds to a heterodimer receptor composed of the specific subunit IL-5Rα and a common subunit βc shared with IL-3 and GM-CSF...
November 17, 2016: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/27826098/a-randomized-multicenter-study-evaluating-xolair%C3%A2-persistency-of-response-after-long-term-therapy-xport
#2
Dennis Ledford, William Busse, Benjamin Trzaskoma, Theodore A Omachi, Karin Rosén, Bradley E Chipps, Allan T Luskin, Paul G Solari
BACKGROUND: Few data are available to assist clinicians with decisions regarding long-term use of asthma therapies, including omalizumab. OBJECTIVE: To evaluate the benefit and persistency of response in subjects continuing or withdrawing from long-term omalizumab treatment. METHODS: Evaluating the Xolair® Persistency Of Response After Long-Term Therapy (XPORT) was a randomized, double-blind, placebo-controlled withdrawal study that included subjects with moderate-to-severe persistent asthma receiving long-term omalizumab...
November 5, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27759482/dermatologic-uses-of-omalizumab
#3
Justin C Chia, P Régine Mydlarski
PURPOSE: Omalizumab is a recombinant humanized monoclonal antibody that inhibits the binding of immunoglobulin E (IgE) to the high-affinity IgE receptor (FceRI) on the surface of mast cells and basophils. Omalizumab has been approved for use in asthma, and new reports show promise in a variety of dermatologic diseases. Herein, we review the literature on omalizumab in dermatology and discuss the safety, efficacy and mechanisms of action for this emerging therapy. MATERIALS AND METHODS: PubMED, MEDLINE and Embase databases were searched for the period 1 January 1990 to 1 September 2016...
November 7, 2016: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/27699264/depletion-of-major-pathogenic-cells-in-asthma-by-targeting-crth2
#4
Tao Huang, Meredith Hazen, Yonglei Shang, Meijuan Zhou, Xiumin Wu, Donghong Yan, Zhonghua Lin, Margaret Solon, Elizabeth Luis, Hai Ngu, Yongchang Shi, Arna Katewa, David F Choy, Nandhini Ramamoorthi, Erick R Castellanos, Mercedesz Balazs, Min Xu, Wyne P Lee, Marissa L Matsumoto, Jian Payandeh, Joseph R Arron, Jo-Anne Hongo, Jianyong Wang, Isidro Hötzel, Cary D Austin, Karin Reif
Eosinophilic inflammation and Th2 cytokine production are central to the pathogenesis of asthma. Agents that target either eosinophils or single Th2 cytokines have shown benefits in subsets of biomarker-positive patients. More broadly effective treatment or disease-modifying effects may be achieved by eliminating more than one inflammatory stimulator. Here we present a strategy to concomitantly deplete Th2 T cells, eosinophils, basophils, and type-2 innate lymphoid cells (ILC2s) by generating monoclonal antibodies with enhanced effector function (19A2) that target CRTh2 present on all 4 cell types...
May 19, 2016: JCI Insight
https://www.readbyqxmd.com/read/27678500/applications-and-mechanisms-of-immunotherapy-in-allergic-rhinitis-and-asthma
#5
Jasper H Kappen, Stephen R Durham, Hans In 't Veen, Mohamed H Shamji
Clinical and immunologic tolerance are hallmarks of successful allergen immunotherapy (AIT). Clinical benefits such as reduced symptoms, pharmacotherapy intake and improvement of quality of life persist following cessation of treatment. Successful AIT is associated with suppression of allergic inflammatory cells such as mast cells, eosinophils and basophils in target organs. Furthermore, AIT down-regulates type 2 innate lymphoid cells and allergen-specific type 2 T-helper (Th2) cells. The immunologic tolerant state following AIT is associated with the induction of distinct phenotypes of regulatory T-cells (T-regs) including interleukin (IL)-10-, IL-35- and transforming growth factor (TGF)-β- producing T-regs and FoxP3(+) T-regs...
September 27, 2016: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/27613653/novel-biologicals-for-the-treatment-of-allergic-diseases-and-asthma
#6
REVIEW
Hern-Tze Tina Tan, Kazunari Sugita, Cezmi A Akdis
PURPOSE OF REVIEW: The development of biological therapies has rapidly progressed during the last few years, and major advances were reported for the treatment of allergic diseases, such as atopic dermatitis, allergic rhinitis, urticaria, food allergy, and asthma. Here, we review biologicals targeting the type 2 immune response involving Th2 cells, type 2 innate lymphoid cells, natural killer T cells, mast cells, basophils, and epithelial cells, such as IL-4, IL-5, IL-13, IL-31, tumor necrosis factor alpha (TNF-α), and thymic stromal lymphopoietin (TSLP)...
October 2016: Current Allergy and Asthma Reports
https://www.readbyqxmd.com/read/27496752/role-of-interleukin-18-in-the-pathophysiology-of-allergic-diseases
#7
Nathan L Sanders, Anil Mishra
Interleukin (IL)-18 is an IL-1 family cytokine expressed by macrophages, dendritic cells, epithelial cells, and keratinocytes and is implicated in various aspects of both the innate and adaptive immune systems. IL-18 signals similar to IL-1β intracellularly to activate gene transcription. Since its discovery, IL-18 has been demonstrated to play a key role in pathogen defense from helminths and some bacteria. Recently however, evidence has accumulated that IL-18 expression is increased in many presentations of allergic disease...
December 2016: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/27432971/alternative-splicing-of-interleukin-33-and-type-2-inflammation-in-asthma
#8
Erin D Gordon, Laura J Simpson, Cydney L Rios, Lando Ringel, Marrah E Lachowicz-Scroggins, Michael C Peters, Agata Wesolowska-Andersen, Jeanmarie R Gonzalez, Hannah J MacLeod, Laura S Christian, Shaopeng Yuan, Liam Barry, Prescott G Woodruff, K Mark Ansel, Karl Nocka, Max A Seibold, John V Fahy
Type 2 inflammation occurs in a large subgroup of asthmatics, and novel cytokine-directed therapies are being developed to treat this population. In mouse models, interleukin-33 (IL-33) activates lung resident innate lymphoid type 2 cells (ILC2s) to initiate airway type 2 inflammation. In human asthma, which is chronic and difficult to model, the role of IL-33 and the target cells responsible for persistent type 2 inflammation remain undefined. Full-length IL-33 is a nuclear protein and may function as an "alarmin" during cell death, a process that is uncommon in chronic stable asthma...
August 2, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27417329/inhibition-of-spleen-tyrosine-kinase-attenuates-ige-mediated-airway-contraction-and-mediator-release-in-human-precision-cut-lung-slices
#9
Cynthia J Koziol-White, Yanlin Jia, Gretchen A Baltus, Philip R Cooper, Dennis M Zaller, Michael A Crackower, Erich E Sirkowski, Steven Smock, Alan B Northrup, Blanca E Himes, Stephen E Alves, Reynold A Panettieri
BACKGROUND AND PURPOSE: Asthma presents as a heterogeneous syndrome characterized by airway obstruction, inflammation and hyper-reactivity (AHR). Spleen tyrosine kinase (Syk) mediates allergen-induced mast cell degranulation, a central component of allergen-induced inflammation and AHR. However, the role of Syk in IgE-mediated constriction of human small airways remains unknown. In this study, we addressed whether selective inhibition of Syk attenuates IgE-mediated constriction and mast cell mediator release in human small airways...
November 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27317944/pharmacological-characterization-of-crth2-antagonist-las191859-long-receptor-residence-time-translates-into-long-lasting-in-vivo-efficacy
#10
Marta Calbet, Miriam Andrés, Clara Armengol, Mónica Bravo, Peter Eichhorn, Rosa López, Vicente García-González, Richard Roberts, Montserrat Miralpeix
The chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells (CRTh2) is a G protein-coupled receptor expressed on the leukocytes most closely associated with asthma and allergy like eosinophils, mast cells, Th2-lymphocytes and basophils. At present it is clear that CRTh2 mediates most prostaglandin D2 (PGD2) pro-inflammatory effects and as a result antagonists for this receptor have reached asthma clinical studies showing a trend of lung function improvement. The challenge remains to identify compounds with improved clinical efficacy when administered once a day...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27193929/-a-case-of-anaphylaxis-in-the-pediatric-patient-with-milk-allergy-due-to-traces-of-milk-protein-in-the-lactose-used-as-an-excipient-of-inavir-inhalation
#11
Miki Morikawa, Yoshitomi Kanemitsu, Hiroki Tsukamoto, Akimasa Morikawa, Yoshihisa Tomioka
The patient was a 6-year-old female with milk allergy and persistent asthma. She experienced anaphylactic reactions just after the inhalation of Inavir (Laninamivir Octanoate Hydrate) to treat flu infection. A skin-prick test showed positive reactions for Inavir inhaler powder and lactose used as an excipient but negative for Laninamivir. Same results were obtained in a drug-stimulated basophil activation test. The lactose excipient in Inavir inhaler powder was supposed to contain milk proteins, which caused anaphylactic reactions...
May 2016: Arerugī, [Allergy]
https://www.readbyqxmd.com/read/27103662/preclinical-safety-profile-of-a-depleting-antibody-against-crth2-for-asthma-well-tolerated-despite-unexpected-crth2-expression-on-vascular-pericytes-in-the-central-nervous-system-and-gastric-mucosa
#12
Kathila S Rajapaksa, Tao Huang, Neeraj Sharma, Shannon Liu, Margaret Solon, Arthur Reyes, Sarah Paul, Angie Yee, Janet Tao, Sreedevi Chalasani, Nga Bien-Ly, Kai Barck, Richard A D Carano, Jianyong Wang, Linda Rangell, Meire Bremer, Dimitry M Danilenko, Paula Katavolos, Isidro Hotzel, Karin Reif, Cary D Austin
CRTh2 is expressed on immune cells that drive asthma pathophysiology. Current treatment options for severe asthma are inadequate and therapeutic antibody-mediated depletion of CRTh2-expressing cells represents a promising new therapeutic strategy. Here we report for the first time that CRTh2 is not only expressed on immune cells, but also on microvasculature in the central nervous system (CNS) and gastric mucosa in humans. Microvascular expression of CRTh2 raises a safety concern because a therapeutic antiCRTh2 antibody with enhanced depletion capacity could lead to vascular damage...
July 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27103607/is-there-a-future-for-biologics-in-the-management-of-chronic-rhinosinusitis
#13
REVIEW
Kent Lam, Robert C Kern, Amber Luong
BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory condition of the sinonasal mucosa consisting of poorly defined subtypes and characterized by variable clinical manifestations, responses to therapy, and underlying pathophysiologies. In the related disorder of asthma, progress has been made in defining disease subtypes on both clinical and pathophysiologic levels, facilitating the development of targeted biologic pharmacotherapy. The potential role of these drugs for the management of CRS will be reviewed...
September 2016: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/27090058/treating-ige-mediated-diseases-via-targeting-ige-expressing-b-cells-using-an-anti-c%C3%AE%C2%B5mx-antibody
#14
REVIEW
Sean S Liour, Andrew Tom, Yueh-Hsuan Chan, Tse Wen Chang
Targeting the IgE pathway is a clinically validated strategy for treating IgE-mediated diseases. Omalizumab, an anti-IgE antibody, which binds to free IgE and prevents the binding of IgE to FcεRI on mast cells and basophils has been approved for severe persistent allergic asthma and chronic spontaneous (idiopathic) urticaria. The therapeutic efficacy of anti-IgE has also been reported in allergic rhinitis, allergic bronchopulmonary aspergillosis, latex allergy, atopic dermatitis, allergic urticaria, anaphylaxis, and others...
August 2016: Pediatric Allergy and Immunology
https://www.readbyqxmd.com/read/27083105/local-allergic-rhinitis
#15
REVIEW
Paloma Campo, María Salas, Natalia Blanca-López, Carmen Rondón
This review focuses on local allergic rhinitis, a new phenotype of allergic rhinitis, commonly misdiagnosed as nonallergic rhinitis. It has gained attention over last decade and can affect patients from all countries, ethnic groups and ages, impairing their quality of life, and is frequently associated with conjunctivitis and asthma. Diagnosis is based on clinical history, the demonstration of a positive response to nasal allergen provocation test and/or the detection of nasal sIgE. A positive basophil activation test may support the diagnosis...
May 2016: Immunology and Allergy Clinics of North America
https://www.readbyqxmd.com/read/27079298/elevated-levels-of-circulating-cd4-crth2-t-cells-characterize-severe-asthma
#16
N S Palikhe, C Laratta, D Nahirney, D Vethanayagam, M Bhutani, H Vliagoftis, L Cameron
BACKGROUND: Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) is a receptor for PGD2 and expressed by T cells, eosinophils, basophils, and ILC2 cells. CRTh2 expression by CD4(+) T cells identifies the Th2 subset, and these cells have been characterized as allergen-specific central memory Th2 cells. Recently, activation of the PGD2 -CRTh2 pathway in the lungs was associated with severe asthma. OBJECTIVE: To assess circulating levels of Th2 cells and related mediators in severe asthma and those who experience asthma exacerbations...
June 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27026044/expression-of-basophil-activation-markers-in-pediatric-asthma
#17
Masooma Abdullahi, Reza Ranjbaran, Soheaila Alyasin, Zeinab Keshavarz, Amin Ramezani, Abbas Behzad-Behbahani, Sedigheh Sharifzadeh
BACKGROUND: Asthma is very common in children and its diagnosis is based on clinical manifestations, which can be misdiagnosed as other respiratory diseases with similar signs and symptoms. OBJECTIVE: To analyze the expression of ST2L and CD203c in the diagnosis of pediatric asthma. METHODS: Basophils were purified from whole blood samples of patients and healthy controls using Ficol-Paque gradient and Basophil Isolation Kit. RNA extraction was done by RNX-Plus solution and after synthesis of cDNA, the gene expression was analyzed by means of real time PCR...
March 2016: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/26953825/years-in-review-recent-progress-in-cellular-allergology
#18
REVIEW
Bernhard Kratzer, Winfried F Pickl
This review highlights the recent key advances in the biology of CD4+ effector T cells, antigen-presenting cells, Th17 and T regulatory cells, as well as immediate effector cells, such as mast cells, basophils and eosinophils, which are critically contributing to the better understanding of the pathophysiology of allergic diseases and are helping to improve their diagnosis and therapy. Some of the key advances with a direct impact on allergic asthma research and treatment are summarized.
2016: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/26945497/immunologic-alterations-and-efficacy-of-subcutaneous-immunotherapy-with-dermatophagoides-pteronyssinus-in-monosensitized-and-polysensitized-patients
#19
Sadan Soyyigit, Deniz Guloglu, Aydan Ikinciogullari, Derya Secil, Derya Oztuna, Dilsad Mungan, Zeynep Misirligil, Betul Ayse Sin
BACKGROUND: There is a continuing debate about whether monoallergen subcutaneous immunotherapy (SCIT) is able to modulate immune and clinical responses toward main causal allergen in polysensitized patients. OBJECTIVE: To investigate short-term immunologic changes and clinical effectiveness of SCIT with Dermatophagoides pteronyssinus in monosensitized and polysensitized patients who have rhinitis with or without asthma. METHODS: Nineteen monosensitized and 24 polysensitized patients participated in this prospective, self-placebo-controlled, interventional study...
March 2016: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/26908079/identification-and-characterization-of-major-cat-allergen-fel-d-1-mimotopes-on-filamentous-phage-carriers
#20
Jernej Luzar, Peter Molek, Mira Šilar, Peter Korošec, Mitja Košnik, Borut Štrukelj, Mojca Lunder
Cat allergy is one of the most prevalent allergies worldwide and can lead to the development of rhinitis and asthma. Thus far, only allergen extracts from natural sources have been used for allergen-specific immunotherapy. However, extracts and whole allergens in immunotherapy present an anaphylaxis risk. Identification of allergen epitopes or mimotopes has an important role in development of safe and effective allergen-specific immunotherapy. Moreover, with a suitable immunogenic carrier, the absence of sufficient immune response elicited by short peptides could be surmounted...
March 2016: Molecular Immunology
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