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  1. Article ; Online: Update on Respiratory Fungal Infections in Cystic Fibrosis Lung Disease and after Lung Transplantation

    Sabine Renner / Edith Nachbaur / Peter Jaksch / Eleonora Dehlink

    Journal of Fungi, Vol 6, Iss 381, p

    2020  Volume 381

    Abstract: Cystic fibrosis is the most common autosomal-recessive metabolic disease in the Western world. Impaired trans-membrane chloride transport via the cystic fibrosis transmembrane conductance regulator (CFTR) protein causes thickened body fluids. In the ... ...

    Abstract Cystic fibrosis is the most common autosomal-recessive metabolic disease in the Western world. Impaired trans-membrane chloride transport via the cystic fibrosis transmembrane conductance regulator (CFTR) protein causes thickened body fluids. In the respiratory system, this leads to chronic suppurative cough and recurrent pulmonary infective exacerbations, resulting in progressive lung damage and respiratory failure. Whilst the impact of bacterial infections on CF lung disease has long been recognized, our understanding of pulmonary mycosis is less clear. The range and detection rates of fungal taxa isolated from CF airway samples are expanding, however, in the absence of consensus criteria and univocal treatment protocols for most respiratory fungal conditions, interpretation of laboratory reports and the decision to treat remain challenging. In this review, we give an overview on fungal airway infections in CF and CF-lung transplant recipients and focus on the most common fungal taxa detected in CF, Aspergillus fumigatus , Candida spp., Scedosporium apiospermum complex , Lomentospora species, and Exophiala dermatitidis , their clinical presentations, common treatments and prophylactic strategies, and clinical challenges from a physician’s point of view.
    Keywords ABPA ; fungi ; respiratory exacerbation ; antifungals ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Lower airway clinical outcome measures for use in primary ciliary dyskinesia research

    Florian Gahleitner / James Thompson / Claire L. Jackson / Jana F. Hueppe / Laura Behan / Eleonora Dehlink / Myrofora Goutaki / Florian Halbeisen / Ana Paula L. Queiroz / Guillaume Thouvenin / Claudia E. Kuehni / Philipp Latzin / Jane S. Lucas / Bruna Rubbo

    ERJ Open Research, Vol 7, Iss

    a scoping review

    2021  Volume 4

    Abstract: Objectives Disease-specific, well-defined and validated clinical outcome measures are essential in designing research studies. Poorly defined outcome measures hamper pooling of data and comparisons between studies. We aimed to identify and describe ... ...

    Abstract Objectives Disease-specific, well-defined and validated clinical outcome measures are essential in designing research studies. Poorly defined outcome measures hamper pooling of data and comparisons between studies. We aimed to identify and describe pulmonary outcome measures that could be used for follow-up of patients with primary ciliary dyskinesia (PCD). Methods We conducted a scoping review by systematically searching MEDLINE, Embase and the Cochrane Database of Systematic Reviews online databases for studies published from 1996 to 2020 that included ≥10 PCD adult and/or paediatric patients. Results We included 102 studies (7289 patients). 83 studies reported on spirometry, 11 on body plethysmography, 15 on multiple-breath washout, 36 on high-resolution computed tomography (HRCT), 57 on microbiology and 17 on health-related quality of life. Measurement and reporting of outcomes varied considerably between studies (e.g. different scoring systems for chest HRCT scans). Additionally, definitions of outcome measures varied (e.g. definition of chronic colonisation by respiratory pathogen), impeding direct comparisons of results. Conclusions This review highlights the need for standardisation of measurements and reporting of outcome measures to enable comparisons between studies. Defining a core set of clinical outcome measures is necessary to ensure reproducibility of results and for use in future trials and prospective cohorts.
    Keywords Medicine ; R
    Subject code 001 ; 610
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher European Respiratory Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: An optimized, robust and reproducible protocol to generate well-differentiated primary nasal epithelial models from extremely premature infants

    Anke Martens / Gabriele Amann / Katy Schmidt / René Gaupmann / Bianca Böhm / Eleonora Dehlink / Zsolt Szépfalusi / Elisabeth Förster-Waldl / Angelika Berger / Nanna Fyhrquist / Harri Alenius / Lukas Wisgrill

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 10

    Abstract: Abstract Extremely premature infants are prone to severe respiratory infections, and the mechanisms underlying this exceptional susceptibility are largely unknown. Nasal epithelial cells (NEC) represent the first-line of defense and adult-derived ALI ... ...

    Abstract Abstract Extremely premature infants are prone to severe respiratory infections, and the mechanisms underlying this exceptional susceptibility are largely unknown. Nasal epithelial cells (NEC) represent the first-line of defense and adult-derived ALI cell culture models show promising results in mimicking in vivo physiology. Therefore, the aim of this study was to develop a robust and reliable protocol for generating well-differentiated cell culture models from NECs of extremely premature infants. Nasal brushing was performed in 13 extremely premature infants at term corrected age and in 11 healthy adult controls to obtain NECs for differentiation at air-liquid interface (ALI). Differentiation was verified using imaging and functional analysis. Successful isolation and differentiation was achieved for 5 (38.5%) preterm and 5 (45.5%) adult samples. Preterm and adult ALI-cultures both showed well-differentiated morphology and ciliary function, however, preterm cultures required significantly longer cultivation times for acquiring full differentiation (44 ± 3.92 vs. 23 ± 1.83 days; p < 0.0001). Moreover, we observed that recent respiratory support may impair successful NECs isolation. Herewithin, we describe a safe, reliable and reproducible method to generate well-differentiated ALI-models from NECs of extremely premature infants. These models provide a valuable foundation for further studies regarding immunological and inflammatory responses and respiratory disorders in extremely premature infants.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2019-12-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Relationships between levels of serum IgE, cell-bound IgE, and IgE-receptors on peripheral blood cells in a pediatric population.

    Eleonora Dehlink / Alexandra H Baker / Elizabeth Yen / Samuel Nurko / Edda Fiebiger

    PLoS ONE, Vol 5, Iss 8, p e

    2010  Volume 12204

    Abstract: Elevated serum immunoglobulin (Ig) E is a diagnostic marker of immediate-type allergic reactions. We hypothesize that serum IgE does not necessarily reflect total body IgE because in vivo IgE can be bound to cell surface receptors such as FcepsilonRI and ...

    Abstract Elevated serum immunoglobulin (Ig) E is a diagnostic marker of immediate-type allergic reactions. We hypothesize that serum IgE does not necessarily reflect total body IgE because in vivo IgE can be bound to cell surface receptors such as FcepsilonRI and FcepsilonRII (CD23). The aim of this study was to analyze the relationships between levels of serum IgE, cell-bound IgE, and IgE-receptors on peripheral blood cells in a pediatric population.Whole blood samples from 48 children (26 boys, 22 girls, mean age 10,3+/-5,4 years) were analyzed by flow cytometry for FcepsilonRI, CD23, and cell-bound IgE on dendritic cells (CD11c+MHC class II+), monocytes (CD14+), basophils (CD123+MHC class II-) and neutrophils (myeloperoxidase+). Total serum IgE was measured by ELISA and converted into z-units to account for age-dependent normal ranges. Correlations were calculated using Spearman rank correlation test.Dendritic cells, monocytes, basophils, and neutrophils expressed the high affinity IgE-receptor FcepsilonRI. Dendritic cells and monocytes also expressed the low affinity receptor CD23. The majority of IgE-receptor positive cells carried IgE on their surface. Expression of both IgE receptors was tightly correlated with cell-bound IgE. In general, cell-bound IgE on FcepsilonRI+ cells correlated well with serum IgE. However, some patients carried high amounts of cell-bound IgE despite low total serum IgE levels.In pediatric patients, levels of age-adjusted serum IgE, cell-bound IgE, and FcepsilonRI correlate. Even in the absence of elevated levels of serum IgE, cell-bound IgE can be detected on peripheral blood cells in a subgroup of patients.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2010-08-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Fc-epsilon-RI, the high affinity IgE-receptor, is robustly expressed in the upper gastrointestinal tract and modulated by mucosal inflammation.

    Christina Bannert / Bettina Bidmon-Fliegenschnee / Georg Stary / Florian Hotzy / Judith Stift / Samuel Nurko / Zsolt Szépfalusi / Edda Fiebiger / Eleonora Dehlink

    PLoS ONE, Vol 7, Iss 7, p e

    2012  Volume 42066

    Abstract: The role of the high affinity IgE receptor, FcεRI, in IgE-mediated immune responses of the gastrointestinal (GI) mucosa is poorly understood. Currently, a detailed characterization of FcεRI expression throughout the human gut is lacking. The aim of this ... ...

    Abstract The role of the high affinity IgE receptor, FcεRI, in IgE-mediated immune responses of the gastrointestinal (GI) mucosa is poorly understood. Currently, a detailed characterization of FcεRI expression throughout the human gut is lacking. The aim of this study was to define the expression pattern of FcεRI in the GI tract.We compared FcεRI expression in children with gastritis/esophagitis (n = 10), celiac disease (n = 10), inflammatory bowel disease (IBD) (n = 9), and normal mucosa (n = 5). The α-subunit of FcεRI (FcεRIα), detected by immunohistochemistry, was found on cells infiltrating the mucosa of the esophagus, the stomach, and the duodenum, but was rarely detected in more distal sections of the GI tract. Accordingly, quantitative RT-PCR analysis on esophagus, stomach, duodenum, colon, and rectum biopsies revealed that FcεRIα and -β expression levels decreased towards the distal intestine. mRNA transcripts of the common Fc-receptor-γ chain were present in the entire GI mucosa. Double-immunofluorescence staining of esophageal specimens confirmed that FcεRIα was expressed on intraepithelial mast cells and Langerhans cells. The mRNA expression levels of the α, β, and γ subunits of FcεRI did not correlate with total serum IgE but were associated with mucosal inflammation.Our data define the upper GI tract as the main site for IgE-mediated immune activation via FcεRI. Tissue mRNA levels of FcεRIα are regulated by inflammatory conditions rather than serum IgE, indicating that FcεRI might also play a role in pathologies other than allergy.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: IgE/FcεRI-Mediated Antigen Cross-Presentation by Dendritic Cells Enhances Anti-Tumor Immune Responses

    Barbara Platzer / Kutlu G. Elpek / Viviana Cremasco / Kristi Baker / Madeleine M. Stout / Cornelia Schultz / Eleonora Dehlink / Kai-Ting C. Shade / Robert M. Anthony / Richard S. Blumberg / Shannon J. Turley / Edda Fiebiger

    Cell Reports, Vol 10, Iss 9, Pp 1487-

    2015  Volume 1495

    Abstract: Epidemiologic studies discovered an inverse association between immunoglobulin E (IgE)-mediated allergies and cancer, implying tumor-protective properties of IgE. However, the underlying immunologic mechanisms remain poorly understood. Antigen cross- ... ...

    Abstract Epidemiologic studies discovered an inverse association between immunoglobulin E (IgE)-mediated allergies and cancer, implying tumor-protective properties of IgE. However, the underlying immunologic mechanisms remain poorly understood. Antigen cross-presentation by dendritic cells (DCs) is of key importance for anti-tumor immunity because it induces the generation of cytotoxic CD8+ T lymphocytes (CTLs) with specificity for tumor antigens. We demonstrate that DCs use IgE and FcεRI, the high-affinity IgE receptor, for cross-presentation and priming of CTLs in response to free soluble antigen at low doses. Importantly, IgE/FcεRI-mediated cross-presentation is a distinct receptor-mediated pathway because it does not require MyD88 signals or IL-12 induction in DCs. Using passive immunization with tumor antigen-specific IgE and DC-based vaccination experiments, we demonstrate that IgE-mediated cross-presentation significantly improves anti-tumor immunity and induces memory responses in vivo. Our findings suggest a cellular mechanism for the tumor-protective features of IgE and expand the known physiological functions of this immunoglobulin.
    Keywords Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2015-03-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: The disease-specific clinical trial network for primary ciliary dyskinesia

    Johanna Raidt / Bernard Maitre / Petra Pennekamp / Josje Altenburg / Pinelopi Anagnostopoulou / Miguel Armengot / Lizan D. Bloemsma / Mieke Boon / Melissa Borrelli / Folke Brinkmann / Siobhan B. Carr / Mary P. Carroll / Silvia Castillo-Corullón / André Coste / Renato Cutrera / Eleonora Dehlink / Damien M.S. Destouches / Maria E. Di Cicco / Lucy Dixon /
    Nagehan Emiralioglu / Ela Erdem Eralp / Eric G. Haarman / Claire Hogg / Bulent Karadag / Helene E. Kobbernagel / Natalie Lorent / Marcus A. Mall / June K. Marthin / Vendula Martinu / Manjith Narayanan / Ugur Ozcelik / Daniel Peckham / Massimo Pifferi / Petr Pohunek / Eva Polverino / Simon Range / Felix C. Ringshausen / Evie Robson / Jobst Roehmel / Sandra Rovira-Amigo / Francesca Santamaria / Anne Schlegtendal / Zsolt Szépfalusi / Petra Tempels / Guillaume Thouvenin / Nicola Ullmann / Woolf T. Walker / Martin Wetzke / Panayiotis Yiallouros / Heymut Omran / Kim G. Nielsen

    ERJ Open Research, Vol 8, Iss

    PCD-CTN

    2022  Volume 3

    Abstract: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and ... ...

    Abstract Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity. To improve clinical and translational research and facilitate development of new treatments, the clinical trial network for PCD (PCD-CTN) was founded in 2020 under the framework of the European Reference Network (ERN)-LUNG PCD Core. Applications from European PCD sites interested in participating in the PCD-CTN were requested. Inclusion criteria consisted of patient numbers, membership of ERN-LUNG PCD Core, use of associated standards of care, experience in PCD and/or CF clinical research, resources to run clinical trials, good clinical practice (GCP) certifications and institutional support. So far, applications from 22 trial sites in 18 European countries have been approved, including >1400 adult and >1600 paediatric individuals with PCD. The PCD-CTN is headed by a coordinating centre and consists of a steering and executive committee, a data safety monitoring board and committees for protocol review, training and standardisation. A strong association with patient organisations and industrial companies are further cornerstones. All participating trial sites agreed on a code of conduct. As CTNs from other diseases have demonstrated successfully, this newly formed PCD-CTN operates to establish evidence-based treatments for this orphan disease and to bring new personalised treatment approaches to patients.
    Keywords Medicine ; R
    Subject code 610
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher European Respiratory Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: A soluble form of the high affinity IgE receptor, Fc-epsilon-RI, circulates in human serum.

    Eleonora Dehlink / Barbara Platzer / Alexandra H Baker / Jessica Larosa / Michael Pardo / Peter Dwyer / Elizabeth H Yen / Zsolt Szépfalusi / Samuel Nurko / Edda Fiebiger

    PLoS ONE, Vol 6, Iss 4, p e

    2011  Volume 19098

    Abstract: Soluble IgE receptors are potential in vivo modulators of IgE-mediated immune responses and are thus important for our basic understanding of allergic responses. We here characterize a novel soluble version of the IgE-binding alpha-chain of Fc-epsilon-RI ...

    Abstract Soluble IgE receptors are potential in vivo modulators of IgE-mediated immune responses and are thus important for our basic understanding of allergic responses. We here characterize a novel soluble version of the IgE-binding alpha-chain of Fc-epsilon-RI (sFcεRI), the high affinity receptor for IgE. sFcεRI immunoprecipitates as a protein of ∼40 kDa and contains an intact IgE-binding site. In human serum, sFcεRI is found as a soluble free IgE receptor as well as a complex with IgE. Using a newly established ELISA, we show that serum sFcεRI levels correlate with serum IgE in patients with elevated IgE. We also show that serum of individuals with normal IgE levels can be found to contain high levels of sFcεRI. After IgE-antigen-mediated crosslinking of surface FcεRI, we detect sFcεRI in the exosome-depleted, soluble fraction of cell culture supernatants. We further show that sFcεRI can block binding of IgE to FcεRI expressed at the cell surface. In summary, we here describe the alpha-chain of FcεRI as a circulating soluble IgE receptor isoform in human serum.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2011-04-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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