Structure of intact IgE and the mechanism of ligelizumab revealed by electron microscopy.


BACKGROUND:IgE is the central antibody isotype in TH2-biased immunity and allergic diseases. The structure of intact IgE and the impact of IgE-targeting molecules on IgE however remain elusive. In order to obtain insights into IgE biology and the clinical impact, we aimed for structure determination of IgE and the complex of IgE with the anti-IgE antibody ligelizumab. METHODS:Structures of two distinct intact IgE with specificity for cross-reactive carbohydrate determinants and Der p 2 as well as complexes of ligelizumab-Fab with IgE and IgE Fc were assessed by negative stain electron microscopy and solution scattering. Inhibition of IgE binding and displacement of receptor-bound IgE were assessed using cellular assays, basophil activation testing and ELIFAB assays. RESULTS:Our data reveal that the investigated IgE molecules share an overall rigid conformation. In contrast to the IgE Fc fragment, the IgE Fc in intact IgE is significantly less asymmetrically bent. The proximal and the distal Fabs are rigidly tethered to the Fc. Binding of ligelizumab to IgE in a 2:1 stoichiometry induces an extended and twofold symmetrical conformation of IgE, which retains a rigid Fab-Fc architecture. Analyses of effector cell activation revealed that ligelizumab inhibits IgE binding without displacing receptor-bound IgE. Together with an interference of CD23 binding, the data underline a functional activity similar to omalizumab. CONCLUSIONS:Our data reveal the first structures of intact IgE suggesting that the IgE Fab is fixed relative to the Fc. Furthermore, we provide a structural rationale for the inhibitory mechanism of ligelizumab.






Jensen RK,Jabs F,Miehe M,Mølgaard B,Pfützner W,Möbs C,Spillner E,Andersen GR




Has Abstract


2020-08-01 00:00:00














  • Decongestant efficacy of desloratadine in patients with seasonal allergic rhinitis.

    abstract::Recent advances in experimental immunologic approaches to seasonal allergic rhinitis (SAR) have led to a shift in the concepts of its pathogenesis. The conventional view of SAR as a local response to inhaled allergens has largely given way to a new view of this disorder as a systemic condition with local tissue manife...


    pub_type: 杂志文章,评审


    authors: Bachert C

    更新日期:2001-01-01 00:00:00

  • Increased circulating platelet microparticles as a potential biomarker in asthma.

    abstract:BACKGROUND:Endothelial (EMPs) and platelet microparticles (PMPs) have been studied as biomarkers in several inflammatory diseases and as central players in intercellular communication. METHODS:In this cross-sectional study, we aimed to assess microparticle levels in asthma. Circulating microparticles and inflammatory ...


    pub_type: 杂志文章


    authors: Duarte D,Taveira-Gomes T,Sokhatska O,Palmares C,Costa R,Negrão R,Guimarães JT,Delgado L,Soares R,Moreira A

    更新日期:2013-08-01 00:00:00

  • Specific immunotherapy in local allergic rhinitis: A randomized, double-blind placebo-controlled trial with Phleum pratense subcutaneous allergen immunotherapy.

    abstract:BACKGROUND:Allergen immunotherapy has been shown to be an effective treatment for local allergic rhinitis (LAR) to house dust mites. Studies with pollen allergen immunotherapy are limited to observational studies. The aim of this study was to evaluate the clinical efficacy and safety of Phleum pratense subcutaneous imm...


    pub_type: 杂志文章,随机对照试验


    authors: Rondón C,Blanca-López N,Campo P,Mayorga C,Jurado-Escobar R,Torres MJ,Canto G,Blanca M

    更新日期:2018-04-01 00:00:00

  • The respiratory system in connective tissue disorders.

    abstract::The connective tissue disorders (also called collagen vascular diseases) represent an heterogeneous group of immunologically mediated inflammatory disorders with a large variety of affected organs besides the lungs. The respiratory system may be involved in all its components: airways, vessels, parenchyma, pleura, res...


    pub_type: 杂志文章,评审


    authors: Crestani B

    更新日期:2005-06-01 00:00:00

  • Monitoring of serologic immune parameters in inflammatory skin diseases.

    abstract::This paper deals with the correlation of clinical scoring and serologic markers of inflammation in atopic dermatitis and psoriasis. Serum eosinophil cationic protein (ECP), soluble interleukin-2 receptor (sIL-2R), total serum IgE, IgG and IgM anti-IgE antibodies, and IgE immune complexes were evaluated in monitoring i...


    pub_type: 杂志文章


    authors: Gebhardt M,Wenzel HC,Hipler UC,Herrmann D,Wollina U

    更新日期:1997-11-01 00:00:00

  • Protein S protects against allergic bronchial asthma by modulating Th1/Th2 balance.

    abstract:BACKGROUND:Bronchial asthma is a chronic disease characterized by inflammation, obstruction, and hyperresponsiveness of the airways. There is currently no curative therapy for asthma. Type 2 helper T cell response plays a critical role in the pathogenesis of the disease. Protein S is a glycoprotein endowed with anticoa...


    pub_type: 杂志文章


    authors: Asayama K,Kobayashi T,D'Alessandro-Gabazza CN,Toda M,Yasuma T,Fujimoto H,Okano T,Saiki H,Takeshita A,Fujiwara K,Fridman D'Alessandro V,Nishihama K,Totoki T,Inoue R,Takei Y,Gabazza EC

    更新日期:2020-09-01 00:00:00

  • Double-blind, placebo-controlled, dose-ranging study of new recombinant hypoallergenic Bet v 1 in an environmental exposure chamber.

    abstract:BACKGROUND:Recombinant allergens offer a tool for improving specific immunotherapy (SIT). OBJECTIVE:To find the optimal dose of a new hypoallergenic folding variant of recombinant Bet v 1 (rBet v 1-FV) as SIT for patients with birch pollen allergy. METHODS:Before SIT, thirty-seven adult patients were exposed for eigh...


    pub_type: 杂志文章,随机对照试验


    authors: Meyer W,Narkus A,Salapatek AM,Häfner D

    更新日期:2013-06-01 00:00:00

  • Allergic disorders in African countries: linking immunology to accurate phenotype.

    abstract::Identification and characterization of risk and protective factors for allergy is important for developing strategies for prevention or treatment. The prevalence of allergy is clearly higher in affluent countries than in developing countries like, e.g. Africa. Especially in urban areas of developing countries, allergy...


    pub_type: 杂志文章,评审


    authors: van Ree R,Yazdanbakhsh M

    更新日期:2007-03-01 00:00:00

  • The burden of nonadherence among adults with asthma: a role for shared decision-making.

    abstract::A shared approach to decision-making framework has been suggested for chronic disease management especially where multiple treatment options exist. Shared decision-making (SDM) requires that both physician and patients are actively engaged in the decision-making process, including information exchange; expressing trea...


    pub_type: 杂志文章,评审


    authors: Pollard S,Bansback N,FitzGerld JM,Bryan S

    更新日期:2017-05-01 00:00:00

  • Anti-Candida albicans IgE and IgG subclasses in sera of patients with allergic bronchopulmonary aspergillosis (ABPA).

    abstract::We performed immunoblotting experiments to determine specific IgE and IgG subclass responses to Candida albicans antigens in allergic bronchopulmonary aspergillosis (ABPA) patients. This is a first report describing C. albicans antigens recognized by serum IgE and IgG subclasses of ABPA patients sensitized to that yea...


    pub_type: 杂志文章


    authors: Roig E,Malo JL,Montplaisir S

    更新日期:1997-04-01 00:00:00

  • Multiple roles of Bet v 1 ligands in allergen stabilization and modulation of endosomal protease activity.

    abstract:BACKGROUND:Over 100 million people worldwide suffer from birch pollen allergy. Bet v 1 has been identified as the major birch pollen allergen. However, the molecular mechanisms of birch allergic sensitization, including the roles of Bet v 1 and other components of the birch pollen extract, remain incompletely understoo...


    pub_type: 杂志文章


    authors: Soh WT,Aglas L,Mueller GA,Gilles S,Weiss R,Scheiblhofer S,Huber S,Scheidt T,Thompson PM,Briza P,London RE,Traidl-Hoffmann C,Cabrele C,Brandstetter H,Ferreira F

    更新日期:2019-12-01 00:00:00

  • Downregulation of polymeric immunoglobulin receptor and secretory IgA antibodies in eosinophilic upper airway diseases.

    abstract:BACKGROUND:Immunoglobulin (Ig) A represents a first-line defence mechanism in the airways, but little is known regarding its implication in upper airway disorders. This study aimed to address the hypothesis that polymeric Ig receptor (pIgR)-mediated secretory IgA immunity could be impaired in chronic upper airway disea...


    pub_type: 杂志文章


    authors: Hupin C,Rombaux P,Bowen H,Gould H,Lecocq M,Pilette C

    更新日期:2013-12-01 00:00:00

  • Alpine climate treatment of atopic dermatitis: a systematic review.

    abstract::Climate therapy has been used for decades in the treatment of atopic dermatitis (AD), but evidence of its effectiveness has not yet been assessed systematically. A systematic literature search in Medline, Embase, and the Cochrane library was performed to identify all original studies concerning alpine climate treatmen...


    pub_type: 杂志文章,meta分析,评审


    authors: Fieten KB,Weststrate AC,van Zuuren EJ,Bruijnzeel-Koomen CA,Pasmans SG

    更新日期:2015-01-01 00:00:00

  • Small-bowel capsule endoscopy in patients with gastrointestinal food allergy.

    abstract:BACKGROUND:Food allergy may present with a plethora of gastrointestinal and extraintestinal symptoms such as abdominal pain, diarrhea, cardiocirculatory symptoms, cutaneous reactions, or rhinitis. Macropathological lesions like lymphofollicular hyperplasia and erosive or ulcerative lesions have seldom been described in...


    pub_type: 杂志文章,随机对照试验


    authors: Hagel AF,de Rossi TM,Zopf Y,Lindner AS,Dauth W,Neurath MF,Raithel M

    更新日期:2012-02-01 00:00:00

  • Histopathological support of antagonism of allergen-induced mast cell mediator release in human skin by a beta-2-agonist.

    abstract::The site of antagonistic action on allergen-induced early skin reactions by the beta 2-agonist terbutaline was studied by light microscopy in 10 atopic subjects. Pretreatment with 1 microgram terbutaline intradermally 5 min prior to challenge with horse dander allergen produced an approximate inhibition of 85 and 55% ...


    pub_type: 杂志文章


    authors: Grönneberg R,Lagerholm B

    更新日期:1986-01-01 00:00:00

  • Pen ch 13 allergen induces secretion of mediators and degradation of occludin protein of human lung epithelial cells.

    abstract:BACKGROUND:Alkaline serine proteases from six prevalent airborne Penicillium and Aspergillus species have been identified as a group of major allergens (group 13). After entering human airways, the allergens are in initial contacts with respiratory epithelial cells. The purpose of this study is to investigate interacti...


    pub_type: 杂志文章


    authors: Tai HY,Tam MF,Chou H,Peng HJ,Su SN,Perng DW,Shen HD

    更新日期:2006-03-01 00:00:00

  • Rhinitis is an independent risk factor for developing cough apart from colds among adults.

    abstract:BACKGROUND:In cross-sectional clinical studies, rhinitis has been shown to be strongly associated with co-existing chronic cough. However, to date, this association has been poorly delineated from a prospective and epidemiological standpoint. METHODS:We used data from the 'Pisa Prospective Study', a population-based l...


    pub_type: 杂志文章


    authors: Guerra S,Sherrill DL,Baldacci S,Carrozzi L,Pistelli F,Di Pede F,Viegi G

    更新日期:2005-03-01 00:00:00

  • Functional and phenotypic analysis of basophils allows determining distinct subtypes in patients with chronic urticaria.

    abstract: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 releva...


    pub_type: 杂志文章


    authors: Rauber MM,Pickert J,Holiangu L,Möbs C,Pfützner W

    更新日期:2017-12-01 00:00:00

  • The role of house dust mite elimination in the management of childhood asthma: an unresolved issue.

    abstract::Indoor allergens are likely to be direct environmental causes of asthma and mite exposure, and sensitization is the most important environmental risk factor for childhood asthma in temperate zones. Analagous to occupational asthma, allergen avoidance in asthmatic children sensitized and exposed to mite allergens is as...


    pub_type: 杂志文章,评审


    authors: Boner A,Pescollderungg L,Silverman M

    更新日期:2002-01-01 00:00:00

  • Neonatal leukocyte cAMP-phosphodiesterase determination is not suitable for allergy prediction.

    abstract::The atopy-predictive value of cord blood (CB) cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE) in mononuclear leukocytes (MN) was studied prospectively in 57 neonates. Reliable determination of cAMP-PDE was achieved in only 20 CB samples. The levels tended to be higher in infants developing signs of atopy u...


    pub_type: 杂志文章


    authors: Odelram H,Björkstén B,Chan SC,Hanifin JM,Kjellman NI

    更新日期:1994-09-01 00:00:00

  • Specificity of ELISA for IgG subclass antibodies against inhalant antigens in early childhood.

    abstract::ELISA is increasingly used to measure antibodies in new circumstances. Recently, it has been applied to the measurement of IgG subclass antibodies against common antigens in early childhood. These studies have raised concerns about the specificity of some of these assays. This paper details the results of experiments ...


    pub_type: 杂志文章


    authors: Ruiz RG,Price JF,Kemeny DM

    更新日期:1994-10-01 00:00:00

  • Prevention and control of childhood asthma and allergy in the EU from the public health point of view: Polish Presidency of the European Union.

    abstract::The leading priority for the Polish Presidency of the Council of the European Union was to reduce health inequalities across European societies, and, within its framework, prevention and control of respiratory diseases in children. This very important paper contain proposal of international cooperation on the preventi...


    pub_type: 共识发展会议,杂志文章,评审


    authors: Samoliński B,Fronczak A,Kuna P,Akdis CA,Anto JM,Bialoszewski AZ,Burney PG,Bush A,Czupryniak A,Dahl R,Flood B,Galea G,Jutel M,Kowalski ML,Palkonen S,Papadopoulos N,Raciborski F,Sienkiewicz D,Tomaszewska A,Von Mutius

    更新日期:2012-06-01 00:00:00

  • Rates of release of subcutaneously injected antigens in the rat. Comparison of an aqueous preparation with two alum-precipated preparations.

    abstract::Release of antigen E-125 I from the site of subcutaneous injection in male rats was delayed significantly when either of two alum-precipitated preparations containing 1.0-1.2 mg of Al/ml was administered rather than an aqueous preparation. The rates of 125I excretion were similarly influenced being statistically slowe...


    pub_type: 杂志文章


    authors: Leeling JL,Muni IA,Helms RJ,Johnson N Jr

    更新日期:1979-10-01 00:00:00

  • Indoor allergen levels in settled airborne dust are higher in day-care centers than at home.

    abstract:BACKGROUND:Early-life sensitization to indoor allergens predicts asthma development. The aim of this study was to compare allergen concentrations in day-care centers (DCC) with those in private homes. METHODS:Settled airborne dust was collected 4 times a year from 20 German DCC (620 samples) and from the homes of chil...


    pub_type: 杂志文章


    authors: Sander I,Lotz A,Neumann HD,Czibor C,Flagge A,Zahradnik E,Raulf M

    更新日期:2018-06-01 00:00:00

  • Characterization of monocyte subtypes in the allergic form of atopic eczema/dermatitis syndrome.

    abstract:BACKGROUND:Monocyte (Mo) subsets exhibiting distinct phenotypic and functional properties identified in peripheral blood are assumed to be under the control of soluble factors from their surrounding micromilieu. Atopic eczema/dermatitis syndrome (AEDS) is accompanied by humoral and cellular alterations among which an i...


    pub_type: 杂志文章


    authors: Novak N,Allam P,Geiger E,Bieber T

    更新日期:2002-10-01 00:00:00

  • Staphylococcus aureus-derived extracellular vesicles induce neutrophilic pulmonary inflammation via both Th1 and Th17 cell responses.

    abstract:BACKGROUND:Recent evidence indicates that Staphylococcus aureus, one of the most important human pathogens, secretes vesicles into the extracellular milieu. OBJECTIVE:To evaluate whether inhalation of S. aureus-derived extracellular vesicles (EV) is causally related to the pathogenesis of inflammatory pulmonary diseas...


    pub_type: 杂志文章


    authors: Kim MR,Hong SW,Choi EB,Lee WH,Kim YS,Jeon SG,Jang MH,Gho YS,Kim YK

    更新日期:2012-10-01 00:00:00

  • How to prescribe antihistamines for chronic idiopathic urticaria: desloratadine daily vs PRN and quality of life.

    abstract:BACKGROUND:Chronic idiopathic urticaria (CIU) impairs quality of life (QoL). Currently, no consensus exists regarding how second-generation H(1)-antihistamines (proven to control CIU symptoms) should be taken long-term: as daily treatment or only when symptoms return (PRN). We sought to determine which regimen improves...


    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Grob JJ,Auquier P,Dreyfus I,Ortonne JP

    更新日期:2009-04-01 00:00:00

  • Is atopic disease a risk factor for attention-deficit/hyperactivity disorder? A systematic review.

    abstract::The increase in prevalence and burden of atopic diseases, i.e. eczema, rhinitis, and asthma over the past decades was paralleled by a worldwide increase in attention-deficit/hyperactivity disorder (ADHD) diagnoses. We systematically reviewed epidemiologic studies investigating the relationship between atopic diseases ...


    pub_type: 杂志文章,评审


    authors: Schmitt J,Buske-Kirschbaum A,Roessner V

    更新日期:2010-12-01 00:00:00

  • Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction.

    abstract:BACKGROUND:Specific oral tolerance induction (SOTI) seems to be a promising treatment of food allergy. Specific oral tolerance induction and elimination diet were compared with respect to efficacy rate and patterns of clinical reaction. METHODS:Children with challenge proven immunoglobulin E (IgE)-mediated cow's milk ...


    pub_type: 杂志文章,随机对照试验


    authors: Staden U,Rolinck-Werninghaus C,Brewe F,Wahn U,Niggemann B,Beyer K

    更新日期:2007-11-01 00:00:00

  • Decreased intercellular adhesion molecule-1 (CD54) and L-selectin (CD62L) expression on peripheral blood natural killer cells in asthmatic children with acute exacerbation.

    abstract:BACKGROUND:The capacity of inflammatory cells to adhere involves an array of adhesion molecules, and is critical to the inflammatory responses seen in childhood asthma. We aimed to determine the changes of intercellular adhesion molecule-1 (ICAM-1) and L-selectin expressed on peripheral blood (PB) T lymphocytes and nat...


    pub_type: 杂志文章


    authors: Lin SJ,Chang LY,Yan DC,Huang YJ,Lin TJ,Lin TY

    更新日期:2003-01-01 00:00:00