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Il 13 antibody severe asthma

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https://www.readbyqxmd.com/read/28584245/immune-signatures-of-pathogenesis-in-the-peritoneal-compartment-during-early-infection-of-sheep-with-fasciola-hepatica
#1
Maria Teresa Ruiz-Campillo, Veronica Molina Hernandez, Alejandro Escamilla, Michael Stevenson, Jose Perez, Alvaro Martinez-Moreno, Sheila Donnelly, John P Dalton, Krystyna Cwiklinski
Immune signatures of sheep acutely-infected with Fasciola hepatica, an important pathogen of livestock and humans were analysed within the peritoneal compartment to investigate early infection. Within the peritoneum, F. hepatica antibodies coincided with an intense innate and adaptive cellular immune response, with infiltrating leukocytes and a marked eosinophilia (49%). However, while cytokine qPCR analysis revealed IL-10, IL-12, IL-13, IL-23 and TGFβ were elevated, these were not statistically different at 18 days post-infection compared to uninfected animals indicating that the immune response is muted and not yet skewed to a Th2 type response that is associated with chronic disease...
June 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28583618/new-anti-eosinophil-drugs-for-asthma-and-copd-targeting-the-trait
#2
REVIEW
Elisabeth H Bel, Anneke Ten Brinke
Asthma and chronic obstructive airways disease (COPD) are prevalent chronic inflammatory airway diseases that are responsible for a large global disease burden. Both diseases are complex and heterogeneous, and are increasingly recognized as overlapping syndromes that may share similar pathophysiologic mechanisms and treatable traits. Eosinophilic airway inflammation is considered the most influential treatable trait of chronic airway disease, and over the last decade several monoclonal antibodies and small molecule therapies have been developed to target this trait...
June 2, 2017: Chest
https://www.readbyqxmd.com/read/28547386/dupilumab-first-global-approval
#3
Matt Shirley
Dupilumab (Dupixent(®)) is a fully human monoclonal antibody directed against the interleukin (IL)-4 receptor α (IL-4Rα) subunit. Dupilumab inhibits the signalling of the type 2 cytokines IL-4 and IL-13 and was co-developed by Regeneron Pharmaceuticals and Sanofi as a potential therapeutic agent for the treatment of atopic or allergic diseases. In March 2017 dupilumab received its first global approval, in the USA, for use in the treatment of adult patients with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable...
May 25, 2017: Drugs
https://www.readbyqxmd.com/read/28526278/biotherapeutics-in-chronic-rhinosinusitis-with-and-without-nasal-polyps
#4
Claus Bachert, Philippe Gevaert, Peter Hellings
In western countries, 85% of chronic rhinosinusitis with nasal polyp disease reveals a type 2 inflammatory pattern with expression of IL-4, -5, and -13 as well as increased concentrations of IgE, whereas chronic rhinosinusitis without nasal polyps merely expresses these biomarkers. The degree of type 2 inflammation furthermore is associated with disease severity, asthma comorbidity, and recurrence of disease after surgery. Therefore, these biomarkers also form the targets for innovative therapeutic approaches such as monoclonal antibodies directed against IgE, IL-5, and IL-4 receptor alpha, blocking the activity of IL-4 and -13...
May 16, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28479600/a-crucial-role-of-the-pd-1h-coinhibitory-receptor-in-suppressing-experimental-asthma
#5
Huafeng Liu, Xin Li, Li Hu, Min Zhu, Bailin He, Liqun Luo, Lieping Chen
Programmed death one homolog (PD-1H) is a cell surface molecule of the B7/CD28 immune modulatory gene family. Although PD-1H has been shown to function as a coinhibitory receptor on T cells to limit naive T-cell activation and proliferation, its role in the regulation of the T-cell response to allergens is unknown. We report here that genetic ablation or blockade of PD-1H drastically promotes pulmonary inflammation with massive accumulation of eosinophils in a mouse model of experimental asthma, indicating a suppressive function of PD-1H in allergic inflammation...
May 8, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28427296/predictors-of-response-to-therapy-with-omalizumab-in-patients-with-severe-allergic-asthma-a-real-life-study
#6
Maria Kallieri, Andriana I Papaioannou, Evgenia Papathanasiou, Polyxeni Ntontsi, Spyridon Papiris, Stelios Loukides
OBJECTIVES: Omalizumab is a recombinant humanized IgG1 monoclonal anti-IgE antibody, used for the treatment of severe refractory allergic asthma. However, not all patients with IgE levels within the limits of administration, respond to treatment. The aim of the present study, was to determine clinical and inflammatory characteristics that could predict response to omalizumab. METHODS: We studied retrospectively patients treated with omalizumab as per GINA guidelines in one asthma tertiary referral center...
April 28, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28287273/novel-monoclonal-treatments-in-severe-asthma
#7
Howraman Meteran, Hanieh Meteran, Celeste Porsbjerg, Vibeke Backer
AIM: To provide a general overview of the current biological treatments and discuss their potential anti-asthmatic effects. DATA SOURCES: We reviewed articles in PubMed found using the search words "Asthma/therapy AND antibodies, monoclonal/therapeutic use AND cytokines." STUDY SELECTIONS: Only articles published in English since 2000 were considered. The search identified 29 studies; 8 additional studies were found by hand search, generating 37 studies...
March 13, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28277826/commonality-of-the-il-4-il-13-pathway-in-atopic-diseases
#8
Namita A Gandhi, Gianluca Pirozzi, Neil M H Graham
Allergy results from an aberrant Type 2 inflammatory response, triggered by a wide range of environmental antigens (allergens) that lead to various immune responses, culminating in the production of immunoglobulin E (IgE). Two key cytokines, interleukin (IL)-4 and IL-13, are critical to the induction and perpetuation of the Type 2 response, and have been implicated in multiple atopic diseases. Area covered: This review summarizes recent milestone developments that have elucidated components of the pathogenesis of atopic diseases such as atopic dermatitis (AD), asthma, and chronic sinusitis with nasal polyposis (CSwNP)...
March 15, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/27942351/therapeutic-interventions-in-severe-asthma
#9
REVIEW
Giorgio Walter Canonica, Gianenrico Senna, Patrick D Mitchell, Paul M O'Byrne, Giovanni Passalacqua, Gilda Varricchi
The present paper addresses severe asthma which is limited to 5-10% of the overall population of asthmatics. However, it accounts for 50% or more of socials costs of the disease, as it is responsible for hospitalizations and Emergency Department accesses as well as expensive treatments. The recent identification of different endotypes of asthma, based on the inflammatory pattern, has led to the development of tailored treatments that target different inflammatory mediators. These are major achievements in the perspective of Precision Medicine: a leading approach to the modern treatment strategy...
2016: World Allergy Organization Journal
https://www.readbyqxmd.com/read/27836376/-new-drugs-for-severe-asthma
#10
REVIEW
Caroline Sattler, Roxane Malrin, Gilles Garcia, Marc Humbert
Asthma is a very frequent disease with complex and heterogenous immunological and clinical features. Daily inhaled steroids are the cornerstone of the current therapeutics sometimes associated with long-acting β2-agonist. This controller treatment is effective and allows to control asthma symptoms for the vast majority of the patients. Severe asthma is characterized by a poor level of control of symptoms, with recurrent exacerbations or a chronic airflow limitation despite an optimal management. Severe asthma remains a difficult diagnosis but we have now studies proving the clinical efficacy or promising data about monoclonal antibodies targeting IgE, IL-5, IL-4 or IL-13...
November 2016: La Presse Médicale
https://www.readbyqxmd.com/read/27766108/co-exposure-to-zymosan-a-and-heat-inactivated-asian-sand-dust-exacerbates-ovalbumin-induced-murine-lung-eosinophilia
#11
Kaori Sadakane, Takamichi Ichinose, Masataka Nishikawa, Hirohisa Takano, Takayuki Shibamoto
BACKGROUND: Epidemiological studies have implicated Asian sand dust (ASD) in the increased prevalence of respiratory disorders, including asthma. It has been observed that fungal elements such as β-glucan can be adsorbed onto ASD. In the present study, the exacerbating effect of the combined exposure to zymosan A (ZymA) containing yeast β-glucan and heat-inactivated ASD on ovalbumin (OVA)-induced murine lung eosinophilia was investigated. METHODS: BALB/c mice were repeatedly instilled intratracheally with one of eight immunogenic formulations consisting of various combinations of (1) ZymA, (2) ASD that was briefly heated to remove organic substances (H-ASD), and (3) OVA in normal saline, or each of the above alone...
2016: Allergy, Asthma, and Clinical Immunology
https://www.readbyqxmd.com/read/27582399/using-periostin-as-a-biomarker-in-the-treatment-of-asthma
#12
REVIEW
Kenji Izuhara, Shoichiro Ohta, Junya Ono
Periostin acts both as an extracellular matrix protein belonging to the fasciclin family and as a matricellular protein functioning in cell activation by binding to its receptors on the cell surface. It has been established that periostin is a downstream molecule of interleukin (IL)-13, a signature type 2 cytokine, and that periostin plays an important role in the pathogenesis of allergic diseases, including asthma. Based on these findings, much attention has been paid to periostin as a biomarker useful in the treatment of asthma...
November 2016: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/27499539/characterization-of-asthma-endotypes-implications-for-therapy
#13
REVIEW
Jeffrey R Stokes, Thomas B Casale
OBJECTIVE: To describe the concept of precision medicine in treating severe asthma and the utility of relevant biomarkers. DATA SOURCES: PubMed was searched for published articles on human clinical trials using biologics for T-helper type 2 cell (TH2)-low and TH2-high asthma. STUDY SELECTIONS: Studies were selected if they were double-masked, randomized, placebo-controlled trials published in peer-reviewed journals and relevant to the topic...
August 2016: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/27459348/biologics-targeting-il-5-il-4-or-il-13-for-the-treatment-of-asthma-an-update
#14
REVIEW
Garry M Walsh
The development of monoclonal antibody-based biologics targeted at inhibition of the Th2 cytokines IL-4, IL-5 and IL-13 represent potentially effective treatments for patients with the glucocorticoid refractory eosinophilic asthma phenotype. Areas covered: Asthma exhibits marked heterogeneity both clinically and at the molecular phenotypic level, requiring specifically targeted treatments to block the key pathways of the disease. It is becoming apparent that significant clinical effects with anti-cytokine-based biologic therapies are more likely in carefully selected patient populations that take asthma phenotypes into account...
February 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/27373855/patient-stratification-and-the-unmet-need-in-asthma
#15
REVIEW
Linda Swedin, Tiiu Saarne, Maria Rehnberg, Pernilla Glader, Magdalena Niedzielska, Gustav Johansson, Petra Hazon, Matthew C Catley
Asthma is often described as an inflammatory disease of the lungs and in most patients symptomatic treatment with bronchodilators or inhaled corticosteroids is sufficient to control disease. Unfortunately there are a proportion of patients who fail to achieve control despite treatment with the best current treatment. These severe asthma patients have been considered a homogeneous group of patients that represent the unmet therapeutic need in asthma. Many novel therapies have been tested in unselected asthma patients and the effects have often been disappointing, particularly for the highly specific monoclonal antibody-based drugs such as anti-IL-13 and anti-IL-5...
January 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27334730/monoclonal-antibodies-for-the-management-of-severe-asthma
#16
Renata Rubinsztajn, Ryszarda Chazan
Asthma is a heterogeneous inflammatory disease. Most patients respond to current standard of care, i.e., bronchodilators, inhaled glucocorticosteroids and other anti-inflammatory drugs, but in some adequate asthma control cannot be achieved with standard treatments. These difficult-to-treat patients would be the target population for new biological therapies. At present, omalizumab is the only biological agent approved for the treatment of early-onset, severe IgE-dependent asthma. It is safe, effective, and well tolerated...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27165851/interleukin-4-receptor-signaling-and-its-binding-mechanism-a-therapeutic-insight-from-inhibitors-tool-box
#17
REVIEW
Zaheer Ul-Haq, Sehrish Naz, M Ahmed Mesaik
Studies on Interlukin-4 (IL-4) disclosed great deal of information about its various physiological and pathological roles. All these roles depend upon its interaction and signaling through either type-I (IL-4Rα/common γ-chain) or type-II (IL-4Rα/IL-13Rα) receptors. Another cytokine, IL-13, shares some of the functions of IL-4, because both cytokines use a common receptor subunit, IL-4Rα. Here in this review, we discuss the structural details of IL-4 and IL-4Rα subunit and the structural similarities between IL-4 and IL-13...
December 2016: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/27161908/lebrikizumab-in-the-treatment-of-asthma
#18
Stephen Bujarski, Amit D Parulekar, Nicola A Hanania
Severe asthma continues to be a major clinical problem despite the availability of effective asthma medications such as inhaled corticosteroids. Several targeted biologic therapies are emerging to treat patients with severe asthma. Areas Covered: This review provides an update of information on lebrikizumab, a novel monoclonal antibody that targets IL-13 and is currently in advanced stages of development. It describes the role of IL-13, a key effector cytokine in Type 2 (T2) airway inflammation in asthma and discusses the results of recent phase 2 trials investigating lebrikizumab's efficacy and safety in patients with severe asthma...
May 10, 2016: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/26895179/pharmacological-therapy-of-bronchial-asthma-the-role-of-biologicals
#19
REVIEW
Sebastian Heck, Juliane Nguyen, Duc-Dung Le, Robert Bals, Quoc Thai Dinh
Bronchial asthma is a heterogeneous, complex, chronic inflammatory and obstructive pulmonary disease driven by various pathways to present with different phenotypes. A small proportion of asthmatics (5-10%) suffer from severe asthma with symptoms that cannot be controlled by guideline therapy with high doses of inhaled steroids plus a second controller, such as long-acting β2 agonists (LABA) or leukotriene receptor antagonists, or even systemic steroids. The discovery and characterization of the pathways that drive different asthma phenotypes have opened up new therapeutic avenues for asthma treatment...
2015: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/26635789/estrogen-signaling-modulates-allergic-inflammation-and-contributes-to-sex-differences-in-asthma
#20
REVIEW
Aleksander Keselman, Nicola Heller
Asthma is a chronic airway inflammatory disease that affects ~300 million people worldwide. It is characterized by airway constriction that leads to wheezing, coughing, and shortness of breath. The most common treatments are corticosteroids and β2-adrenergic receptor antagonists, which target inflammation and airway smooth muscle constriction, respectively. The incidence and severity of asthma is greater in women than in men, and women are more prone to develop corticosteroid-resistant or "hard-to-treat" asthma...
2015: Frontiers in Immunology
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