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https://www.readbyqxmd.com/read/28651294/-ige-and-anti-ige-in-asthma-a-chequered-history
#1
M Lommatzsch, K Geißler, K-C Bergmann, J Christian Virchow
A long and winding road led to the discovery of immunoglobulin E (IgE) in 1966 and 1967. We are currently on a long and winding road to understand the immunologic basis of the clinical effects of the anti-IgE antibody omalizumab in asthma. It is possible that patients with asthma (as patients with chronic spontaneous urticaria) benefit in different immunologic ways from omalizumab treatment. This article reviews the history of IgE discovery and current concepts of anti-IgE therapy in asthma.
June 2017: Pneumologie
https://www.readbyqxmd.com/read/28647457/quantitative-in-vitro-and-in-vivo-models-to-assess-human-ige-b-cell-receptor-crosslinking-by-ige-and-empd-ige-targeting-antibodies
#2
Benjamin Vigl, Nina Salhat, Michela Parth, Halyna Pankevych, Andreas Mairhofer, Stefan Bartl, Oskar W Smrzka
Targeting plasma IgE by therapeutic mABs like Omalizumab (Xolair®) is current clinical practice for severe allergic conditions or other IgE related diseases like chronic urticaria. As an alternative to soluble IgE targeting, IgE supply can be lowered by targeting the Extracellular Membrane Proximal Domain (EMPD) of the IgE B cell receptor (BCR) present on IgE switched B cells. This ultimately leads to apoptosis of these cells upon IgE BCR crosslinking. Since tools to selectively assess the efficacy of IgE BCR crosslinking by IgE targeting antibodies are limited, a readily quantifiable cell model was developed that allows to specifically address IgE BCR crosslinking activity in vitro...
June 21, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28635659/divergent-how-ige-axis-contributes-to-the-continuum-of-allergic-asthma-and-anti-ige-therapies
#3
REVIEW
Óscar Palomares, Silvia Sánchez-Ramón, Ignacio Dávila, Luis Prieto, Luis Pérez de Llano, Marta Lleonart, Christian Domingo, Antonio Nieto
Asthma is an airway disease characterised by chronic inflammation with intermittent or permanent symptoms including wheezing, shortness of breath, chest tightness, and cough, which vary in terms of their occurrence, frequency, and intensity. The most common associated feature in the airways of patients with asthma is airway inflammation. In recent decades, efforts have been made to characterise the heterogeneous clinical nature of asthma. The interest in improving the definitions of asthma phenotypes and endotypes is growing, although these classifications do not always correlate with prognosis nor are always appropriate therapeutic approaches...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28622052/biologic-treatment-eligibility-for-real-world-patients-with-severe-asthma-the-ideal-study
#4
Frank C Albers, Hana Müllerová, Necdet B Gunsoy, Ji-Yeon Shin, Linda M Nelsen, Eric S Bradford, Sarah M Cockle, Robert Y Suruki
OBJECTIVES: Severe asthma comprises several distinct phenotypes. Consequently, patients with severe asthma can be eligible for more than one biologic treatment targeting Th2 inflammation, such as anti-interleukin (IL)-5 and anti-immunoglobulin (Ig) E. The objective of this study was to describe treatment eligibility and overlap in treatment eligibility for mepolizumab (anti-IL-5), omalizumab (anti-IgE) and reslizumab (anti-IL-5) in patients with severe asthma, who were recruited from clinical practice...
June 16, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28585360/functional-and-phenotypic-analysis-of-basophils-allows-determining-distinct-subtypes-in-patients-with-chronic-urticaria
#5
Michèle Myriam Rauber, Julia Pickert, Lily Holiangu, Christian Möbs, Wolfgang Pfützner
BACKGROUND: Chronic urticaria (CU) is a frequent skin disease characterized by relapsing appearance of pruritic hives. While clinical symptoms are due to the release of histamine by cutaneous mast cells, the underlying pathophysiology is still unknown. However, previous studies indicate that basophils might be of relevance. Besides, the occurrence of autoantibodies against IgE or its receptor, FcεRI, and the therapeutic efficacy of anti-IgE antibodies imply that IgE-mediated mechanisms also play an important role in CU...
June 5, 2017: Allergy
https://www.readbyqxmd.com/read/28567072/hyperimmunoglobulin-e-syndrome-genetics-immunopathogenesis-clinical-findings-and-treatment-modalities
#6
REVIEW
Hassan Hashemi, Masoumeh Mohebbi, Shiva Mehravaran, Mehdi Mazloumi, Hamidreza Jahanbani-Ardakani, Seyed-Hossein Abtahi
The hyperimmunoglobulin E syndromes (HIESs) are very rare immunodeficiency syndromes with multisystem involvement, including immune system, skeleton, connective tissue, and dentition. HIES are characterized by the classic triad of high serum levels of immunoglobulin E (IgE), recurrent staphylococcal cold skin abscess, and recurrent pneumonia with pneumatocele formation. Most cases of HIES are sporadic although can be inherited as autosomal dominant and autosomal recessive traits. A fundamental immunologic defect in HIES is not clearly elucidated but abnormal neutrophil chemotaxis due to decreased production or secretion of interferon γ has main role in the immunopathogenesis of syndrome, also distorted Th1/Th2 cytokine profile toward a Th2 bias contributes to the impaired cellular immunity and a specific pattern of infection susceptibility as well as atopic-allergic constitution of syndrome...
2017: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/28535776/the-role-of-anti-ige-omalizumab-xolair-in-the-management-of-severe-recalcitrant-paediatric-atopic-eczema-adapt-statistical-analysis-plan
#7
Tao Chen, Susan Chan, Gideon Lack, Suzie Cro, Victoria R Cornelius
BACKGROUND: The Atopic Dermatitis Anti-IgE Paediatric Trial (ADAPT) is a trial to determine the clinical efficacy and safety of omalizumab for children with severe atopic eczema. This article describes the detailed statistical analysis plan for the ADAPT as an update to the published protocol and is submitted prior to knowing all outcomes. METHOD AND DESIGN: The ADAPT is a randomised, double-blind, placebo-controlled trial with a primary objective to determine whether anti-IgE reduces eczema severity as assessed by the validated eczema score (objective SCORAD) after 24 weeks of treatment in children with severe eczema...
May 23, 2017: Trials
https://www.readbyqxmd.com/read/28517027/lung-function-parameters-in-omalizumab-responder-patients-an-interesting-tool
#8
F Paganin, G Mangiapan, A Proust, A Prudhomme, J Attia, S Marchand-Adam, F Pellet, F Milhe, B Melloni, A Bernady, C Raspaud, C Nocent, P Berger, L Guilleminault
BACKGROUND: Omalizumab, an anti-IgE antibody, is used to treat patients with severe allergic asthma. The evolution of lung function parameters over time and the difference between omalizumab responder and non-responder patients remain inconclusive. The objective of this real-life study was to compare the changes in FEV1 of omalizumab responders and non-responders at 6 months. METHODS: A multicenter analysis was performed in 10 secondary and tertiary institutions...
May 18, 2017: Allergy
https://www.readbyqxmd.com/read/28516039/a-plane-screw-fixation-is-a-nidus-for-paecilomyces-sinusitis-in-a-patient-with-aspirin-exacerbated-respiratory-disease
#9
Anthony M Szema, Cyrus Jo
Titanium plane screw fixation of the frontal sinus is an approach used by otolaryngologists to obliterate this space in an attempt to reduce sinus infections. In this case, however, the titanium used became a nidus of infection which cultured the fungus Paecilomyces. The patient also had a hypersensitivity reaction to mold with positive skin tests and IgE, as well as eosinophilic esophagitis. Treatment entailed anti-fungals, anti-IgE, and fungal immunotherapy to multiple fungal antigens prevalent to the geographic region...
2017: IDCases
https://www.readbyqxmd.com/read/28483235/basophil-activation-test-for-inhalant-allergens-in-pediatric-patients-with-allergic-rhinitis
#10
Ismail Ogulur, Ayca Kiykim, Safa Baris, Ahmet Ozen, Ezgi Gizem Yuce, Elif Karakoc-Aydiner
OBJECTIVE: Flow cytometric quantification of in vitro basophil activation can be quite performant and reliable tool to measure IgE-dependent allergen-specific responses in allergic patients. Current study aimed to evaluate the clinical relevance of basophil activation test (BAT) for the diagnosis of pediatric grass pollen and house dust mite (HDM) allergies. METHODS: Forty-seven patients suffering from allergic rhinitis with HDM and grass pollen co-sensitization with clinical history of allergic rhinitis and/or asthma and 15 non-allergic healthy subjects were enrolled...
June 2017: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/28464704/prospects-for-new-and-emerging-therapeutics-in-severe-asthma-the-role-of-biologics
#11
Seçil Kepil Özdemir, Sevim Bavbek
Asthma is a common and heterogeneous disease. While current conventional therapies are effective in the majority of the patients, a significant subgroup remain uncontrolled despite these treatments. Different biological agents are currently approved or undergoing development for treatment of asthma, including anti-IgE, anti-interleukin (IL)-5, anti-IL-13, anti-IL-4 and anti-thymic stromal lymphopoietin agents. This review will focus on the currently available evidence regarding the new and emerging biological agents in severe asthma...
June 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28442583/seletalisib-characterization-of-a-novel-potent-and-selective-inhibitor-of-pi3k%C3%AE
#12
Rodger A Allen, Daniel C Brookings, Mark J Powell, Jean Delgado, Lindsay K Shuttleworth, Mark Merriman, Ian J Fahy, Roohi Tewari, John P Silva, Louise J Healy, Gareth C G Davies, Breda Twomey, Rona M Cutler, Apoorva Kotian, Andrea Crosby, Gillian McCluskey, Gillian F Watt, Andrew Payne
Phosphoinositide 3-kinases (PI3K) are key signaling enzymes regulating cellular survival, development, and function. Expression of the PI3Kδ isoform is largely restricted to leukocytes and it plays a key role in immune cell development and function. Seletalisib is a novel small-molecule inhibitor of PI3Kδ that was evaluated in biochemical assays, cellular assays of adaptive and innate immunity, and an in vivo rat model of inflammation. Our findings show that seletalisib is a potent, ATP-competitive, and selective PI3Kδ inhibitor able to block protein kinase B (AKT) phosphorylation following activation of the B-cell receptor in a B-cell line...
June 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28441991/in-vitro-impact-of-anti-immunoglobulin-e-monoclonal-antibodies-including-omalizumab-on-whole-blood-basophil-histamine-release-assessment-of-direct-induction-of-basophil-histamine-release-and-evaluation-of-modulation-of-allergen-induced-basophil-histamine-release
#13
Krzysztof Kowal, Pawel Bielecki, Ilona V DuBuske, Lawrence M DuBuske
AIM: The aim of this study was to evaluate the potential of anti-immunoglobulin E (IgE) and/or anti-IgE-IgE immune complexes to release histamine from peripheral blood basophils. In addition, a potential modulating effect of anti-IgE-IgE complexes on allergen-induced peripheral blood basophil histamine release was evaluated. METHODS: Whole blood basophil histamine release (WBB-HR) tests done by using glass-fiber-based microtiter plates were performed in 62 patients with allergic rhinitis and/or asthma sensitized to perennial allergens...
May 1, 2017: Allergy and Asthma Proceedings:
https://www.readbyqxmd.com/read/28439933/effect-of-anti-ige-in-occupational-asthma-caused-by-exposure-to-low-molecular-weight-agents
#14
M Ollé-Monge, M J Cruz, S Gomez-Ollés, I Ojanguren, J Vanoirbeek, X Muñoz
BACKGROUND: The role of immunoglobulin (Ig)-E in occupational asthma (OA) due to low molecular weight (LMW) agents is not well established compared to classical atopic asthma. In the present study we evaluate whether anti-IgE monoclonal antibody (mAb) has an effect in a mouse model of OA, using persulfate salts. METHODS: On days 1 and 8, BALB/C mice were dermally sensitized with 5% ammonium persulfate (AP) or dimethyl sulfoxide (DMSO). On days 15, 18 and 21 animals were injected intraperitoneally with anti-IgE mAb or PBS 6 hours before challenge with AP or saline...
April 25, 2017: Allergy
https://www.readbyqxmd.com/read/28438838/allosteric-mechanism-of-action-of-the-therapeutic-anti-ige-antibody-omalizumab
#15
Anna M Davies, Elizabeth G Allan, Anthony H Keeble, Jean Delgado, Benjamin P Cossins, Alkistis N Mitropoulou, Marie O Y Pang, Tom Ceska, Andrew J Beavil, Graham Craggs, Marta Westwood, Alistair J Henry, James M McDonnell, Brian J Sutton
Immunoglobulin E and its interactions with receptors FcϵRI and CD23 play a central role in allergic disease. Omalizumab, a clinically approved therapeutic antibody, inhibits the interaction between IgE and FcϵRI, preventing mast cell and basophil activation, and blocks IgE binding to CD23 on B cells and antigen-presenting cells. We solved the crystal structure of the complex between an omalizumab-derived Fab and IgE-Fc, with one Fab bound to each Cϵ3 domain. Free IgE-Fc adopts an acutely bent structure, but in the complex it is only partially bent, with large-scale conformational changes in the Cϵ3 domains that inhibit the interaction with FcϵRI...
June 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28435464/clinical-efficacy-of-omalizumab-in-chronic-spontaneous-urticaria-is-associated-with-a-reduction-of-fc%C3%AE%C2%B5ri-positive-cells-in-the-skin
#16
Martin Metz, Petra Staubach, Andrea Bauer, Randolf Brehler, Janine Gericke, Michael Kangas, Joanna Ashton-Chess, Philip Jarvis, Panayiotis Georgiou, Janice Canvin, Rainer Hillenbrand, Veit J Erpenbeck, Marcus Maurer
Background. Treatment with omalizumab, a humanized recombinant monoclonal anti-IgE antibody, results in clinical efficacy in patients with Chronic Spontaneous Urticaria (CSU). The mechanism of action of omalizumab in CSU has not been elucidated in detail. Objectives. To determine the effects of omalizumab on levels of high affinity IgE receptor-positive (FcεRI(+)) and IgE-positive (IgE(+)) dermal cells and blood basophils. Treatment efficacy and safety were also assessed. Study design. In a double-blind study, CSU patients aged 18‑75 years were randomized to receive 300 mg omalizumab (n=20) or placebo (n=10) subcutaneously every 4 weeks for 12 weeks...
2017: Theranostics
https://www.readbyqxmd.com/read/28429307/emerging-approaches-to-food-desensitization-in-children
#17
REVIEW
Ahmad Hamad, Wesley A Burks
PURPOSE OF REVIEW: The purpose of this review is to highlight the recent advances in food desensitization in children with food allergy. RECENT FINDINGS: Recent advancements in epicutaneous, sublingual, and oral immunotherapy for food allergy in the future may offer children with food allergy and their families a viable option to reduce risk or severity of anaphylaxis with phase III trials ongoing for two of these treatment modalities. Food allergy prevalence in children is estimated to be up to 8%...
May 2017: Current Allergy and Asthma Reports
https://www.readbyqxmd.com/read/28427296/predictors-of-response-to-therapy-with-omalizumab-in-patients-with-severe-allergic-asthma-a-real-life-study
#18
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/28401621/mouse-models-of-severe-asthma-understanding-the-mechanisms-of-steroid-resistance-tissue-remodelling-and-disease-exacerbation
#19
REVIEW
Steven Maltby, Hock L Tay, Ming Yang, Paul S Foster
Severe asthma has significant disease burden and results in high healthcare costs. While existing therapies are effective for the majority of asthma patients, treatments for individuals with severe asthma are often ineffective. Mouse models are useful to identify mechanisms underlying disease pathogenesis and for the preclinical assessment of new therapies. In fact, existing mouse models have contributed significantly to our understanding of allergic/eosinophilic phenotypes of asthma and facilitated the development of novel targeted therapies (e...
April 11, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28396318/blocking-allergic-reaction-through-targeting-surface-bound-ige-with-low-affinity-anti-ige-antibodies
#20
Ke Zhang, Jeffrey Liu, Thao Truong, Elyssa Zukin, Wendy Chen, Andrew Saxon
Allergic disorders have now become a major worldwide public health issue, but the effective treatment options remain limited. We report a novel approach to block allergic reactivity by targeting the surface-bound IgE of the allergic effector cells via low-affinity anti-human IgE Abs with dissociation constants in the 10(-6) to 10(-8) M range. We demonstrated that these low-affinity anti-IgE mAbs bind to the cell surface-bound IgE without triggering anaphylactic degranulation even at high concentration, albeit they would weakly upregulate CD203c expression on basophils...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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