2,487 results on '"2723 Immunology and Allergy"'
Search Results
52. Leukocyte redistribution as immunological biomarker of corticosteroid resistance in severe asthma
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Cardoso‐Vigueros, Carlos, von Blumenthal, Tobias, Rückert, Beate, Rinaldi, Arturo O, Tan, Ge, Dreher, Anita, Radzikowska, Urszula, Menz, Günter, Schmid-Grendelmeier, Peter, Akdis, Cezmi A, Sokolowska, Milena, University of Zurich, and Sokolowska, Milena
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2403 Immunology ,Environmental Biomarkers ,Immunology ,10177 Dermatology Clinic ,610 Medicine & health ,Allergens ,Immunoglobulin E ,Asthma ,Eosinophils ,Leukocyte Count ,Adrenal Cortex Hormones ,10183 Swiss Institute of Allergy and Asthma Research ,Leukocytes ,2723 Immunology and Allergy ,Humans ,Immunology and Allergy ,Biomarkers - Abstract
Earlier studies have suggested that the leukocyte redistribution can be considered as an immunological marker of the clinical response to corticosteroids (CS), representing an easy measurable potential biomarker in severe asthma.The aim of this study was to determinate the utility of the leukocyte redistribution as a biomarker of disease heterogeneity in patients with severe asthma and as a bioindicator of potential CS resistance.We developed an unbiased clustering approach based on the clinical data and the flow cytometry results of peripheral blood leukocyte phenotypes of 142 patients with severe asthma before and after systemic CS administration.Based on the differences in the blood count eosinophils, neutrophils and lymphocytes, together with the flow cytometry measurements of basic T cell, B cell and NK cell subpopulations before and after systemic CS administration, we identified two severe asthma clusters, which differed in the cell frequencies, response to CS and atopy status. Patients in cluster 1 had higher frequency of blood eosinophils at baseline, were sensitized to less allergens and had better steroid responsiveness, measured as the pronounced leukocyte redistribution after the administration of systemic CS. Patients in cluster 2 were determined by the higher frequency of B-cells and stronger IgE sensitization status to the multiple allergens. They also displayed higher steroid resistance, as the clinical correlate for the lower leukocyte redistribution after administration of systemic CS.The flow cytometry-based profiling of the basic populations of immune cells in the blood and its analysis before and after systemic corticosteroid administration could improve personalized treatment approaches in patients with severe asthma.
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- 2022
53. Role of dietary fiber in promoting immune health—An EAACI position paper
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Venter, Carina, Meyer, Rosan W, Greenhawt, Matthew, et al, Roduit, Caroline, Akdis, Cezmi A, Sokolowska, Milena, and University of Zurich
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2403 Immunology ,10183 Swiss Institute of Allergy and Asthma Research ,Immunology ,10033 Clinic for Immunology ,2723 Immunology and Allergy ,Immunology and Allergy ,610 Medicine & health - Published
- 2022
54. Effectiveness and safety of tocilizumab in patients with systemic sclerosis: a propensity score matched controlled observational study of the EUSTAR cohort
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Kuster, Simon, Jordan, Suzana, Elhai, Muriel, Held, Ulrike, Steigmiller, Klaus, Bruni, Cosimo, et al, Distler, Oliver, University of Zurich, and Distler, Oliver
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2403 Immunology ,2745 Rheumatology ,10051 Rheumatology Clinic and Institute of Physical Medicine ,2723 Immunology and Allergy ,610 Medicine & health ,10060 Epidemiology, Biostatistics and Prevention Institute (EBPI) - Published
- 2022
55. Stratification in systemic sclerosis according to autoantibody status versus skin involvement: a study of the prospective EUSTAR cohort
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Elhai, Muriel, Sritharan, Nanthara, Boubaya, Marouane, Balbir-Gurman, Alexandra, Siegert, Elise, Hachulla, Eric, de Vries-Bouwstra, Jeska, Riemekasten, Gabriela, Distler, Jörg H W, Rosato, Edoardo, Del Galdo, Francesco, Mendoza, Fabian A, Furst, Daniel E, de la Puente, Carlos, Hoffmann-Vold, Anna-Maria, Gabrielli, Armando, Distler, Oliver, Bloch-Queyrat, Coralie, Allanore, Yannick, Matucci Cerinic, Marco, Walker, Ulrich, Iannone, Florenzo, Jordan, Suzana, Becvar, Radim, Kowal Bielecka, Otylia, Cutolo, Maurizio, Cuomo, Giovanna, Kedor, Claudia, Rednic, Simona, Avouac, Jérome, et al, University of Zurich, and Allanore, Yannick
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2403 Immunology ,Rheumatology ,2745 Rheumatology ,Immunology ,10051 Rheumatology Clinic and Institute of Physical Medicine ,2723 Immunology and Allergy ,Immunology and Allergy ,610 Medicine & health - Published
- 2022
56. BAM! Pathogen control at the brain border
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Sebastian A, Stifter, Melanie, Greter, University of Zurich, and Greter, Melanie
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2403 Immunology ,Macrophages ,Immunology ,Brain ,610 Medicine & health ,2725 Infectious Diseases ,10263 Institute of Experimental Immunology ,Mice ,Meninges ,Infectious Diseases ,Choroid Plexus ,2723 Immunology and Allergy ,Animals ,570 Life sciences ,biology ,Immunology and Allergy - Abstract
Border-associated macrophages (BAMs) reside at the interface between the brain and the periphery, including the meninges and choroid plexus. In this issue of Immunity, two studies report the dynamics, diversity, and fate of murine BAMs during infection, assigning these cells a neuroprotective role.
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- 2022
57. The protean roles of neuroinflammation in trauma, infections, autoimmunity and neurodegeneration
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Aguzzi, Adriano, University of Zurich, and Aguzzi, Adriano
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Inflammation ,2403 Immunology ,Immunology ,10208 Institute of Neuropathology ,2723 Immunology and Allergy ,Humans ,570 Life sciences ,biology ,Immunology and Allergy ,Autoimmunity ,Neurodegenerative Diseases ,610 Medicine & health - Published
- 2022
58. Importance of examining atopic dermatitis disease mechanisms in African populations
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Lunjani, Nonhlanhla, Akdis, Cezmi A, O'Mahony, Liam, University of Zurich, and O'Mahony, Liam
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2403 Immunology ,10183 Swiss Institute of Allergy and Asthma Research ,Immunology ,2723 Immunology and Allergy ,Immunology and Allergy ,610 Medicine & health - Published
- 2022
59. Advances and highlights in asthma in 2021
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Catalina Cojanu, Ibon Eguiluz-Gracia, Magdalena Zemelka-Wiacek, Ioana Agache, Alexandru Laculiceanu, Marek Jutel, Cezmi A. Akdis, Stefano Del Giacco, Anna Kosowska, University of Zurich, and Agache, Ioana
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medicine.medical_specialty ,Severe asthma ,Immunology ,Asthma treatment ,610 Medicine & health ,Context (language use) ,Panel report ,exacerbations ,10183 Swiss Institute of Allergy and Asthma Research ,Artificial Intelligence ,immune system diseases ,Pandemic ,medicine ,Humans ,Immunology and Allergy ,guidelines ,Intensive care medicine ,Asthma ,2403 Immunology ,Biological Products ,business.industry ,biomarkers ,asthma ,medicine.disease ,Planetary health ,respiratory tract diseases ,Clinical trial ,endotypes ,2723 Immunology and Allergy ,business - Abstract
Last year brought a significant advance in asthma management, unyielding to the pressure of the pandemics. Novel key findings in asthma pathogenesis focus on the resident cell compartment, epigenetics and the innate immune system. The precision immunology unbiased approach was supplemented with novel tools and greatly facilitated by the use of artificial intelligence. Several randomised clinical trials and good quality real-world evidence shed new light on asthma treatment and supported the revision of several asthma guidelines (GINA, Expert Panel Report 3, ERS/ATS guidelines on severe asthma) and the conception of new ones (EAACI Guidelines for the use of biologicals in severe asthma). Integrating asthma management within the broader context of Planetary Health has been put forward. In this review, recently published articles and clinical trials are summarised and discussed with the goal to provide clinicians and researchers with a concise update on asthma research from a translational perspective.
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- 2021
60. The Role of Regional Disease and Patterns of Treatment Failure in Primary Sinonasal Malignancies
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Martina A. Broglie, Christian M Meerwein, Domenic Vital, Michael B. Soyka, Panagiotis Balermpas, David Holzmann, University of Zurich, and Meerwein, Christian M
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medicine.medical_specialty ,medicine.medical_treatment ,Regional Disease ,610 Medicine & health ,10045 Clinic for Otorhinolaryngology ,Malignancy ,Disease-Free Survival ,Treatment failure ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Immunology and Allergy ,Treatment Failure ,030223 otorhinolaryngology ,Lymph node ,Neoplasm Staging ,Retrospective Studies ,business.industry ,Outcome measures ,Original Articles ,General Medicine ,medicine.disease ,10044 Clinic for Radiation Oncology ,Radiation therapy ,2733 Otorhinolaryngology ,medicine.anatomical_structure ,Otorhinolaryngology ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,2723 Immunology and Allergy ,Radiology ,business - Abstract
Background The question how to treat the clinically negative neck in sinonasal malignancies is controversial. Objectives To investigate patterns of treatment failure and to assess outcome measures in patients with primary sinonasal malignancies. Methods Retrospective cohort study of patients treated for primary malignant sinonasal malignancies. Results Lymph node (LN) metastases at initial presentation were present in 8 of 152 patients (5.3%). Ipsi- and contralateral LN levels 1 and 2 were identified as nodal basins at risk. We found a 5-year overall survival (OS) of 75.2% and disease free survival of 61.1%. Among patients with cN0 neck, nodal recurrence free survival was not different between patients with and without elective neck treatment ( P = .23). On logistic regression analysis, we found initial T classification as an independent factor for achievement of complete remission (CR) and OS. Conclusions LN metastases at initial presentation are rare and initial T classification was identified as the most important prognostic factor for OS and CR, emphasizing the need for a thorough initial staging of the primary tumor.
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- 2021
61. Cutaneous and systemic hyperinflammation drives maculopapular drug exanthema in severely ill COVID‐19 patients
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Marie-Charlotte Brüggen, Claudia Lang, Angelo V. Marzano, Saskia Oro, Isabel Kolm, Daniel Schulz, Ge Tan, Nicolas de Prost, Mitchell P. Levesque, Peter Schmid-Grendelmeier, Yasutaka Mitamura, Olivier Caudin, Corinne Isabelle Stoffel, Nick Li, Peter Steiger, Cezmi A. Akdis, Bernd Bodenmiller, Reihane Ziadlou, Emanual Michael Maverakis, University of Zurich, and Brüggen, Marie-Charlotte
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Proteomics ,Allergy ,drug‐induced maculopapular exanthema ,coronavirus ,CD8-Positive T-Lymphocytes ,medicine.disease_cause ,SARS‐CoV‐2 ,10183 Swiss Institute of Allergy and Asthma Research ,Immunology and Allergy ,Cytotoxic T cell ,Eosinophilia ,Coronavirus ,education.field_of_study ,medicine.diagnostic_test ,10177 Dermatology Clinic ,medicine.anatomical_structure ,Pharmaceutical Preparations ,2723 Immunology and Allergy ,Original Article ,10023 Institute of Intensive Care Medicine ,medicine.symptom ,Biotechnology ,COVID-19 ,Drug-induced maculopapular exanthema ,SARS-CoV-2 ,drug-induced maculopapular exanthema ,T cell ,Immunology ,Population ,610 Medicine & health ,COVID‐19 ,medicine ,Humans ,education ,2403 Immunology ,business.industry ,Inflammatory and immune system ,Original Articles ,Exanthema ,Eosinophil ,medicine.disease ,Good Health and Well Being ,Skin biopsy ,Cytokine storm ,business ,11493 Department of Quantitative Biomedicine ,CD8 - Abstract
Background Coronavirus disease-2019 (COVID-19) has been associated with cutaneous findings, some being the result of drug hypersensitivity reactions such as maculopapular drug rashes (MDR). The aim of this study was to investigate whether COVID-19 may impact the development of the MDR. Methods Blood and skin samples from COVID-19 patients (based on a positive nasopharyngeal PCR) suffering from MDR (COVID-MDR), healthy controls, non-COVID-19—related patients with drug rash with eosinophilia and systemic symptoms (DRESS), and MDR were analyzed. We utilized imaging mass cytometry (IMC) to characterize the cellular infiltrate in skin biopsies. Furthermore, RNA sequencing transcriptome of skin biopsy samples and high-throughput multiplexed proteomic profiling of serum were performed. Results IMC revealed by clustering analyses a more prominent, phenotypically shifted cytotoxic CD8+ T cell population and highly activated monocyte/macrophage (Mo/Mac) clusters in COVID-MDR. The RNA sequencing transcriptome demonstrated a more robust cytotoxic response in COVID-MDR skin. However, severe acute respiratory syndrome coronavirus 2 was not detected in skin biopsies at the time point of MDR diagnosis. Serum proteomic profiling of COVID-MDR patients revealed upregulation of various inflammatory mediators (IL-4, IL-5, IL-6, TNF, and IFN-γ), eosinophil and Mo/Mac -attracting chemokines (MCP-2, MCP-3, MCP-4 and CCL11). Proteomics analyses demonstrated a massive systemic cytokine storm in COVID-MDR compared with the relatively milder cytokine storm observed in DRESS, while MDR did not exhibit such features. Conclusion A systemic cytokine storm may promote activation of Mo/Mac and cytotoxic CD8+ T cells in severe COVID-19 patients, which in turn may impact the development of MDR., Allergy, 77 (2), ISSN:0105-4538, ISSN:1398-9995
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- 2021
62. One Health: EAACI Position Paper on coronaviruses at the human‐animal interface, with a specific focus on comparative and zoonotic aspects of SARS‐CoV‐2
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Erika Jensen-Jarolim, Jozef Janda, Anna D. J. Korath, Isabella Pali-Schöll, Wojciech Feleszko, Milena Sokolowska, Eva Untersmayr, Ahmed Adel Seida, Katrin Hartmann, Ioana Agache, University of Zurich, and Pali‐Schöll, Isabella
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Eaaci Position Paper ,Immunology ,coronavirus ,610 Medicine & health ,Disease ,medicine.disease_cause ,Quality of life (healthcare) ,10183 Swiss Institute of Allergy and Asthma Research ,Environmental health ,Pandemic ,medicine ,Animals ,Humans ,Immunology and Allergy ,One Health ,Pandemics ,Coronavirus ,disease transmission ,(reverse) zoonosis ,2403 Immunology ,SARS-CoV-2 ,Transmission (medicine) ,COVID-19 ,Outbreak ,companion animals and pets ,Geography ,2723 Immunology and Allergy ,Quality of Life ,Position paper - Abstract
The latest outbreak of a coronavirus disease in 2019 (COVID‐19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), evolved into a worldwide pandemic with massive effects on health, quality of life, and economy. Given the short period of time since the outbreak, there are several knowledge gaps on the comparative and zoonotic aspects of this new virus. Within the One Health concept, the current EAACI position paper dwells into the current knowledge on SARS‐CoV‐2’s receptors, symptoms, transmission routes for human and animals living in close vicinity to each other, usefulness of animal models to study this disease and management options to avoid intra‐ and interspecies transmission. Similar pandemics might appear unexpectedly and more frequently in the near future due to climate change, consumption of exotic foods and drinks, globe‐trotter travel possibilities, the growing world population, the decreasing production space, declining room for wildlife and free‐ranging animals, and the changed lifestyle including living very close to animals. Therefore, both the society and the health authorities need to be aware and well prepared for similar future situations, and research needs to focus on prevention and fast development of treatment options (medications, vaccines).
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- 2021
63. CISH constrains the tuft–ILC2 circuit to set epithelial and immune tone
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Richard M. Locksley, Maya E. Kotas, Christoph Schneider, Roberto R. Ricardo-Gonzalez, Andrew Schroeder, Satoshi Koga, Hong-Erh Liang, Nicholas M. Mroz, University of Zurich, and Locksley, Richard M
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0301 basic medicine ,medicine.medical_treatment ,Immunology ,Fluorescent Antibody Technique ,610 Medicine & health ,Suppressor of Cytokine Signaling Proteins ,Biology ,Article ,10052 Institute of Physiology ,law.invention ,Host-Parasite Interactions ,Immunomodulation ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,law ,Immunity ,medicine ,Immunology and Allergy ,Animals ,Nippostrongylus brasiliensis ,CISH ,Mice, Knockout ,2403 Immunology ,Effector ,Innate lymphoid cell ,biology.organism_classification ,Immunity, Innate ,Lymphocyte Subsets ,Cell biology ,Disease Models, Animal ,030104 developmental biology ,Cytokine ,Host-Pathogen Interactions ,2723 Immunology and Allergy ,570 Life sciences ,biology ,Suppressor ,Cytokines ,Biomarkers ,030215 immunology - Abstract
Innate lymphoid cells (ILCs) are tissue-resident effectors poised to activate rapidly in response to local signals such as cytokines. To preserve homeostasis, ILCs must employ multiple pathways, including tonic suppressive mechanisms, to regulate their primed state and prevent inappropriate activation and immunopathology. Such mechanisms remain incompletely characterized. Here we show that cytokine-inducible SH2-containing protein (CISH), a suppressor of cytokine signaling (SOCS) family member, is highly and constitutively expressed in type 2 innate lymphoid cells (ILC2s). Mice that lack CISH either globally or conditionally in ILC2s show increased ILC2 expansion and activation, in association with reduced expression of genes inhibiting cell-cycle progression. Augmented proliferation and activation of CISH-deficient ILC2s increases basal and inflammation-induced numbers of intestinal tuft cells and accelerates clearance of the model helminth, Nippostrongylus brasiliensis, but compromises innate control of Salmonella typhimurium. Thus, CISH constrains ILC2 activity both tonically and after perturbation, and contributes to the regulation of immunity in mucosal tissue.
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- 2021
64. A Systematic Molecular Epidemiology Screen Reveals Numerous Human Immunodeficiency Virus (HIV) Type 1 Superinfections in the Swiss HIV Cohort Study
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Chaudron, Sandra E, Leemann, Christine, Kusejko, Katharina, Nguyen, Huyen, Tschumi, Nadine, Marzel, Alex, Huber, Michael, Böni, Jürg, Perreau, Matthieu, Klimkait, Thomas, Yerly, Sabine, Ramette, Alban, Hirsch, Hans H, Rauch, Andri, Calmy, Alexandra, Vernazza, Pietro, Bernasconi, Enos, Cavassini, Matthias, Metzner, Karin J, Kouyos, Roger D, Günthard, Huldrych F, and University of Zurich
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10028 Institute of Medical Virology ,10234 Clinic for Infectious Diseases ,2723 Immunology and Allergy ,610 Medicine & health ,2725 Infectious Diseases - Published
- 2022
65. Embryonic and neonatal waves generate distinct populations of hepatic ILC1s
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Colin Sparano, Darío Solís-Sayago, Anjali Vijaykumar, Chiara Rickenbach, Marijne Vermeer, Florian Ingelfinger, Gioana Litscher, André Fonseca, Caroline Mussak, Maud Mayoux, Christin Friedrich, César Nombela-Arrieta, Georg Gasteiger, Burkhard Becher, Sonia Tugues, University of Zurich, and Tugues, Sonia
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2403 Immunology ,Immunology ,610 Medicine & health ,General Medicine ,10263 Institute of Experimental Immunology ,Immunity, Innate ,Killer Cells, Natural ,Mice ,Fetus ,Liver ,10032 Clinic for Oncology and Hematology ,2723 Immunology and Allergy ,Animals ,570 Life sciences ,biology - Abstract
Group 1 innate lymphoid cells (ILCs) comprising circulating natural killer (cNK) cells and tissue-resident ILC1s are critical for host defense against pathogens and tumors. Despite a growing understanding of their role in homeostasis and disease, the ontogeny of group 1 ILCs remains largely unknown. Here, we used fate mapping and single-cell transcriptomics to comprehensively investigate the origin and turnover of murine group 1 ILCs. Whereas cNK cells are continuously replaced throughout life, we uncovered tissue-dependent development and turnover of ILC1s. A first wave of ILC1s emerges during embryogenesis in the liver and transiently colonizes fetal tissues. After birth, a second wave quickly replaces ILC1s in most tissues apart from the liver, where they layer with embryonic ILC1s, persist until adulthood, and undergo a specific developmental program. Whereas embryonically derived ILC1s give rise to a cytotoxic subset, the neonatal wave establishes the full spectrum of ILC1s. Our findings uncover key ontogenic features of murine group 1 ILCs and their association with cellular identities and functions.
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- 2022
66. Complement downregulation promotes an inflammatory signature that renders colorectal cancer susceptible to immunotherapy
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Krieg, C, Weber, LM, Fosso, B, Marzano, M, Hardiman, G, Olcina, MM, Domingo, E, El Aidy, S, Mallah, K, Robinson, MD, Guglietta, S, Host-Microbe Interactions, University of Zurich, and Guglietta, Silvia
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Cancer Research ,Anaphylatoxins ,Immunology ,Down-Regulation ,Mice ,SDG 3 - Good Health and Well-being ,Tumor Microenvironment ,Immunology and Allergy ,Animals ,Humans ,Immunologic Factors ,1306 Cancer Research ,Immune Checkpoint Inhibitors ,Basic tumor immunology ,Gastrointestinal Neoplasms ,Pharmacology ,Inflammation ,2403 Immunology ,Immunity, Innate ,10124 Institute of Molecular Life Sciences ,Disease Models, Animal ,3004 Pharmacology ,Oncology ,1313 Molecular Medicine ,2723 Immunology and Allergy ,570 Life sciences ,biology ,Molecular Medicine ,2730 Oncology ,Disease Susceptibility ,Immunotherapy ,Colorectal Neoplasms - Abstract
Background and aimsThe role of inflammatory immune responses in colorectal cancer (CRC) development and response to therapy is a matter of intense debate. While inflammation is a known driver of CRC, inflammatory immune infiltrates are a positive prognostic factor in CRC and predispose to response to immune checkpoint blockade (ICB) therapy. Unfortunately, over 85% of CRC cases are primarily unresponsive to ICB due to the absence of an immune infiltrate, and even the cases that show an initial immune infiltration can become refractory to ICB. The identification of therapy supportive immune responses in the field has been partially hindered by the sparsity of suitable mouse models to recapitulate the human disease. In this study, we aimed to understand how the dysregulation of the complement anaphylatoxin C3a receptor (C3aR), observed in subsets of patients with CRC, affects the immune responses, the development of CRC, and response to ICB therapy.MethodsWe use a comprehensive approach encompassing analysis of publicly available human CRC datasets, inflammation-driven and newly generated spontaneous mouse models of CRC, and multiplatform high-dimensional analysis of immune responses using microbiota sequencing, RNA sequencing, and mass cytometry.ResultsWe found that patients’ regulation of the complement C3aR is associated with epigenetic modifications. Specifically, downregulation of C3ar1 in human CRC promotes a tumor microenvironment characterized by the accumulation of innate and adaptive immune cells that support antitumor immunity. In addition, in vivo studies in our newly generated mouse model revealed that the lack of C3a in the colon activates a microbiota-mediated proinflammatory program which promotes the development of tumors with an immune signature that renders them responsive to the ICB therapy.ConclusionsOur findings reveal that C3aR may act as a previously unrecognized checkpoint to enhance antitumor immunity in CRC. C3aR can thus be exploited to overcome ICB resistance in a larger group of patients with CRC.
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- 2022
67. Managing food allergy: GA2LEN guideline 2022
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Muraro, Antonella, de Silva, Debra, Halken, Susanne, Worm, Margitta, et al, Ballmer-Weber, Barbara, University of Zurich, and Muraro, Antonella
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Pulmonary and Respiratory Medicine ,2403 Immunology ,2740 Pulmonary and Respiratory Medicine ,Immunology ,2723 Immunology and Allergy ,10177 Dermatology Clinic ,Immunology and Allergy ,610 Medicine & health - Published
- 2022
68. Dersimelagon, a novel oral melanocortin 1 receptor agonist, demonstrates disease-modifying effects in preclinical models of systemic sclerosis
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Kondo, Masahiro, Suzuki, Tsuyoshi, Kawano, Yuko, Kojima, Shinji, Miyashiro, Masahiko, Matsumoto, Atsuhiro, Kania, Gabriela, Błyszczuk, Przemysław, Ross, Rebecca L, Mulipa, Panji, Del Galdo, Francesco, Zhang, Yun, Distler, Jörg H W, and University of Zurich
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Inflammation ,2403 Immunology ,Scleroderma, Systemic ,2745 Rheumatology ,10051 Rheumatology Clinic and Institute of Physical Medicine ,Endothelial Cells ,610 Medicine & health ,Blood Proteins ,Pneumonia ,Fibroblasts ,Fibrosis ,Bleomycin ,Disease Models, Animal ,Mice ,Transforming Growth Factor beta ,2723 Immunology and Allergy ,Animals ,Humans ,ddc:610 ,Receptor, Melanocortin, Type 1 ,Signal Transduction ,Skin - Abstract
Background Activation of melanocortin 1 receptor (MC1R) is known to exert broad anti-inflammatory and anti-fibrotic effects. The purpose of this study is to investigate the potential of dersimelagon, a novel oral MC1R agonist, as a therapeutic agent for systemic sclerosis (SSc). Methods The effects of dersimelagon phosphoric acid (MT-7117) on skin fibrosis and lung inflammation were evaluated in bleomycin (BLM)-induced SSc murine models that were optimized for prophylactic and therapeutic evaluation. Microarray-based gene expression analysis and serum protein profiling were performed in the BLM-induced SSc models. The effect of MT-7117 on transforming growth factor-β (TGF-β)-induced activation of human dermal fibroblasts was evaluated in vitro. Immunohistochemical analyses of MC1R expression in the skin of SSc patients were performed. Results Prophylactic treatment with MT-7117 (≥ 0.3 mg/kg/day p.o.) significantly inhibited skin fibrosis and lung inflammation, and therapeutic treatment with MT-7117 (≥ 3 mg/kg/day p.o.) significantly suppressed the development of skin fibrosis in the BLM-induced SSc models. Gene array analysis demonstrated that MT-7117 exerts an anti-inflammatory effect via suppression of the activation of inflammatory cells and inflammation-related signals; additionally, vascular dysfunction was extracted as the pathology targeted by MT-7117. Serum protein profiling revealed that multiple SSc-related biomarkers including P-selectin, osteoprotegerin, cystatin C, growth and differentiation factor-15, and S100A9 were suppressed by MT-7117. MT-7117 inhibited the activation of human dermal fibroblasts by suppressing TGF-β-induced ACTA2 (encoding α-smooth muscle actin) mRNA elevation. MC1R was expressed by monocytes/macrophages, neutrophils, blood vessels (endothelial cells), fibroblasts, and epidermis (keratinocytes) in the skin of SSc patients, suggesting that these MC1R-positive cells could be targets for MT-7117. Conclusions MT-7117 demonstrates disease-modifying effects in preclinical models of SSc. Investigations of its mechanism of action and target expression analyses indicate that MT-7117 exerts its positive effect by affecting inflammation, vascular dysfunction, and fibrosis, which are all key pathologies of SSc. The results of the present study suggest that MT-7117 is a potential therapeutic agent for SSc. A phase 2 clinical trial investigating the efficacy and tolerability of MT-7117 in patients with early, progressive diffuse cutaneous SSc is currently in progress.
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- 2022
69. Risk factors for severe reactions in food allergy: Rapid evidence review with meta‐analysis
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Turner, Paul J, Arasi, Stefania, Ballmer-Weber, Barbara, Baseggio Conrado, Alessia, Deschildre, Antoine, Gerdts, Jennifer, Halken, Susanne, Muraro, Antonella, Patel, Nandinee, Van Ree, Ronald, de Silva, Debra, Worm, Margitta, Zuberbier, Torsten, Roberts, Graham, University of Zurich, and Turner, Paul J
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2403 Immunology ,Immunology ,2723 Immunology and Allergy ,10177 Dermatology Clinic ,Immunology and Allergy ,610 Medicine & health - Published
- 2022
70. Transcriptome profiles of latently- and reactivated HIV-1 infected primary CD4+ T cells: A pooled data-analysis
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Inderbitzin, Anne, Loosli, Tom, Opitz, Lennart, Rusert, Peter, Metzner, Karin J., University of Zurich, and Metzner, Karin J
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10028 Institute of Medical Virology ,10234 Clinic for Infectious Diseases ,2403 Immunology ,Latently HIV-1 infected primary CD4+ T cells ,Pooled data-analysis ,HIV-1 latency reversal agents ,Pooled data-analysis differentially expressed genes (pdaDEGs) ,2723 Immunology and Allergy ,Primary CD4+ T cell models of HIV-1 latency ,610 Medicine & health ,Reactivated HIV-1 infected primary CD4+ T cells ,Transcriptome profile - Abstract
The main obstacle to cure HIV-1 is the latent reservoir. Antiretroviral therapy effectively controls viral replication, however, it does not eradicate the latent reservoir. Latent CD4+ T cells are extremely rare in HIV-1 infected patients, making primary CD4+ T cell models of HIV-1 latency key to understanding latency and thus finding a cure. In recent years several primary CD4+ T cell models of HIV-1 latency were developed to study the underlying mechanism of establishing, maintaining and reversing HIV-1 latency. In the search of biomarkers, primary CD4+ T cell models of HIV-1 latency were used for bulk and single-cell transcriptomics. A wealth of information was generated from transcriptome analyses of different primary CD4+ T cell models of HIV-1 latency using latently- and reactivated HIV-1 infected primary CD4+ T cells. Here, we performed a pooled data-analysis comparing the transcriptome profiles of latently- and reactivated HIV-1 infected cells of 5 in vitro primary CD4+ T cell models of HIV-1 latency and 2 ex vivo studies of reactivated HIV-1 infected primary CD4+ T cells from HIV-1 infected individuals. Identifying genes that are differentially expressed between latently- and reactivated HIV-1 infected primary CD4+ T cells could be a more successful strategy to better understand and characterize HIV-1 latency and reactivation. We observed that natural ligands and coreceptors were predominantly downregulated in latently HIV-1 infected primary CD4+ T cells, whereas genes associated with apoptosis, cell cycle and HLA class II were upregulated in reactivated HIV-1 infected primary CD4+ T cells. In addition, we observed 5 differentially expressed genes that co-occurred in latently- and reactivated HIV-1 infected primary CD4+ T cells, one of which, MSRB2, was found to be differentially expressed between latently- and reactivated HIV-1 infected cells. Investigation of primary CD4+ T cell models of HIV-1 latency that mimic the in vivo state remains essential for the study of HIV-1 latency and thus providing the opportunity to compare the transcriptome profile of latently- and reactivated HIV-1 infected cells to gain insights into differentially expressed genes, which might contribute to HIV-1 latency., Frontiers in Immunology, 13, ISSN:1664-3224
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- 2022
71. Effects of non-steroidal anti-inflammatory drugs and other eicosanoid pathway modifiers on antiviral and allergic responses: EAACI task force on eicosanoids consensus report in times of COVID-19
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Sokolowska, Milena, Rovati, G Enrico, Diamant, Zuzana, Untersmayr, Eva, Schwarze, Jürgen, Lukasik, Zuzanna, Sava, Florentina, Angelina, Alba, Palomares, Oscar, Akdis, Cezmi A, et al, University of Zurich, and Sokolowska, Milena
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2403 Immunology ,10183 Swiss Institute of Allergy and Asthma Research ,Immunology ,2723 Immunology and Allergy ,Immunology and Allergy ,610 Medicine & health - Published
- 2022
72. Monkeypox outbreak in Europe, UK, North America, and Australia: A changing trend of a zoonotic disease
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Cabanillas, Beatriz, Valdelvira, Rafael, Akdis, Cezmi A, University of Zurich, and Cabanillas, Beatriz
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2403 Immunology ,10183 Swiss Institute of Allergy and Asthma Research ,Immunology ,2723 Immunology and Allergy ,Immunology and Allergy ,610 Medicine & health - Published
- 2022
73. How to counter the anti-vaccine rhetoric: Filling information voids and building resilience
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Germani, Federico, Biller-Andorno, Nikola, University of Zurich, and Biller-Andorno, Nikola
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Pharmacology ,2403 Immunology ,3004 Pharmacology ,Immunology ,10222 Institute of Biomedical Ethics and History of Medicine ,2723 Immunology and Allergy ,Immunology and Allergy ,610 Medicine & health - Abstract
Widely circulating anti-vaccine misinformation online has been constituting a large obstacle for the success of COVID-19 vaccination campaigns and for the well-being of people during the pandemic. In this paper we discuss strategies to mitigate negative effects of online anti-vaccine contents on public health and to prevent hesitant individuals from falling prey of the traps set by anti-vaccine disinformation spreaders. Here we discuss the importance of filling information voids and understanding trends and concerns that shape the vaccine debate, and we highlight the relevance of building resilience to vaccine misinformation by strengthening public health and digital literacy.
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- 2022
74. World Health Organization global air quality guideline recommendations: Executive summary
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Anna Goshua, Cezmi A. Akdis, Kari C. Nadeau, University of Zurich, and Nadeau, Kari C
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Air Pollutants ,2403 Immunology ,Ozone ,10183 Swiss Institute of Allergy and Asthma Research ,Air Pollution ,Nitrogen Dioxide ,Immunology ,2723 Immunology and Allergy ,Humans ,Immunology and Allergy ,Particulate Matter ,610 Medicine & health ,World Health Organization - Abstract
Air pollution is a leading cause of death globally and has resulted in the loss of millions of healthy years of life. Moreover, the health burden has fallen disproportionately upon people in many low- and middle-income countries, where air quality continues to deteriorate. To assist authorities and civil society in improving air quality, World Health Organization has published the first global update to its 2005 air quality guidelines based on a significantly improved body of evidence. To facilitate the implementation of the World Health Organization Global Air Quality Guideline recommendations, this article summarizes the purpose and rationale of the quantitative air quality guidelines and interim target levels for six key pollutants: particulate matter 2.5, particulate matter 10, sulfur dioxide, nitrogen dioxide, ozone, and carbon monoxide. In addition, good practice statements are established for the management of pollutants of concern that lack sufficient evidence to substantiate numerical targets.
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- 2022
75. Monocyte-derived alveolar macrophages autonomously determine severe outcome of respiratory viral infection
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Fengqi Li, Federica Piattini, Lea Pohlmeier, Qian Feng, Hubert Rehrauer, Manfred Kopf, University of Zurich, and Kopf, Manfred
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2403 Immunology ,Immunology ,610 Medicine & health ,10071 Functional Genomics Center Zurich ,General Medicine ,Monocytes ,Mice ,Influenza A virus ,Influenza, Human ,Macrophages, Alveolar ,2723 Immunology and Allergy ,Animals ,Humans ,570 Life sciences ,biology ,Lung - Abstract
Various lung insults can result in replacement of resident alveolar macrophages (AM) by bone marrow monocyte–derived (BMo)–AM. However, the dynamics of this process and its long-term consequences for respiratory viral infections remain unclear. Using several mouse models and a marker to unambiguously track fetal monocyte–derived (FeMo)–AM and BMo-AM, we established the kinetics and extent of replenishment and their function to recurrent influenza A virus (IAV) infection. A massive loss of FeMo-AM resulted in rapid replenishment by self-renewal of survivors, followed by the generation of BMo-AM. BMo-AM progressively outcompeted FeMo-AM over several months, and this was due to their increased glycolytic and proliferative capacity. The presence of both naïve and experienced BMo-AM conferred severe pathology to IAV infection, which was associated with a proinflammatory phenotype. Furthermore, upon aging of naïve mice, FeMo-AM were gradually replaced by BMo-AM, which contributed to IAV disease severity in a cell-autonomous manner. Together, our results suggest that the origin rather than training of AM determines long-term function to respiratory viral infection and provide an explanation for the increased severity of infection seen in the elderly.
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- 2022
76. Efficacy of anti-PD-1 and ipilimumab alone or in combination in acral melanoma
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Bhave, Prachi, Ahmed, Tasnia, Lo, Serigne N, Shoushtari, Alexander, Zaremba, Anne, Versluis, Judith M, Mangana, Joanna, Weichenthal, Michael, Si, Lu, Lesimple, Thierry, Robert, Caroline, Trojanello, Claudia, Wicky, Alexandre, Heywood, Richard, Tran, Lena, Batty, Kathleen, Dimitriou, Florentia, Stansfeld, Anna, Allayous, Clara, Schwarze, Julia K, Mooradian, Meghan J, Klein, Oliver, Mehmi, Inderjit, Roberts-Thomson, Rachel, Maurichi, Andrea, Yeoh, Hui-Ling, Khattak, Adnan, Zimmer, Lisa, Blank, Christian U, Ramelyte, Egle, et al, and University of Zurich
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Pharmacology ,2403 Immunology ,Cancer Research ,Immunology ,10177 Dermatology Clinic ,610 Medicine & health ,3004 Pharmacology ,Oncology ,1313 Molecular Medicine ,2723 Immunology and Allergy ,Molecular Medicine ,Immunology and Allergy ,2730 Oncology ,1306 Cancer Research - Published
- 2022
77. Profound dysregulation of T cell homeostasis and function in patients with severe COVID‐19
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Sujana Sivapatham, Sarah Adamo, Dominik J. Schaer, Melina Stüssi-Helbling, Stéphane Chevrier, Miro E. Raeber, Esther Baechli, Jakob Nilsson, Lars C. Huber, Andrea Jacobs, Liliane Yang, Alain Rudiger, Carlo Cervia, Bernd Bodenmiller, Onur Boyman, Yves Zurbuchen, University of Zurich, Bodenmiller, Bernd, Boyman, Onur, and Nilsson, Jakob
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T cell ,Immunology ,Cell ,T cells ,610 Medicine & health ,macromolecular substances ,Disease ,Lymphocyte Activation ,Asymptomatic ,SARS‐CoV‐2 ,Flow cytometry ,COVID‐19 ,medicine ,COVID-19 ,lymphopenia ,SARS-CoV-2 ,Homeostasis ,Humans ,Autoimmunity and Clinical Immunology ,Immunology and Allergy ,Cytotoxic T cell ,Mass cytometry ,2403 Immunology ,medicine.diagnostic_test ,business.industry ,Cross-Sectional Studies ,medicine.anatomical_structure ,10033 Clinic for Immunology ,2723 Immunology and Allergy ,Original Article ,10029 Clinic and Policlinic for Internal Medicine ,ORIGINAL ARTICLES ,medicine.symptom ,business ,11493 Department of Quantitative Biomedicine - Abstract
Background Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and shows a broad clinical presentation ranging from asymptomatic infection to fatal disease. A very prominent feature associated with severe COVID-19 is T cell lymphopenia. However, homeostatic and functional properties of T cells are ill-defined in COVID-19. Methods We prospectively enrolled individuals with mild and severe COVID-19 into our multicenter cohort and performed a cross-sectional analysis of phenotypic and functional characteristics of T cells using 40-parameter mass cytometry, flow cytometry, targeted proteomics, and functional assays. Results Compared with mild disease, we observed strong perturbations of peripheral T cell homeostasis and function in severe COVID-19. Individuals with severe COVID-19 showed T cell lymphopenia and redistribution of T cell populations, including loss of naïve T cells, skewing toward CD4+T follicular helper cells and cytotoxic CD4+ T cells, and expansion of activated and exhausted T cells. Extensive T cell apoptosis was particularly evident with severe disease and T cell lymphopenia, which in turn was accompanied by impaired T cell responses to several common viral antigens. Patients with severe disease showed elevated interleukin-7 and increased T cell proliferation. Furthermore, patients sampled at late time points after symptom onset had higher T cell counts and improved antiviral T cell responses. Conclusion Our study suggests that severe COVID-19 is characterized by extensive T cell dysfunction and T cell apoptosis, which is associated with signs of homeostatic T cell proliferation and T cell recovery., Allergy, 76 (9), ISSN:0105-4538, ISSN:1398-9995
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- 2021
78. Allergenic components of the mRNA‐1273 vaccine for COVID‐19: Possible involvement of polyethylene glycol and IgG‐mediated complement activation
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Natalija Novak, Jean Bousquet, Cezmi A. Akdis, Beatriz Cabanillas, Ludger Klimek, Marek Jutel, University of Zurich, and Klimek, Ludger
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0301 basic medicine ,Allergy ,COVID-19 Vaccines ,Tromethamine ,Immunology ,Reviews ,610 Medicine & health ,Review ,Polyethylene Glycols ,03 medical and health sciences ,0302 clinical medicine ,10183 Swiss Institute of Allergy and Asthma Research ,Humans ,Immunology and Allergy ,Medicine ,Anaphylaxis ,Complement Activation ,2403 Immunology ,SARS-CoV-2 ,business.industry ,Pseudoallergy ,COVID-19 ,Allergens ,medicine.disease ,United States ,Complement system ,Antibody opsonization ,Vaccination ,Basophil activation ,030104 developmental biology ,030228 respiratory system ,Immunoglobulin G ,2723 Immunology and Allergy ,business ,2019-nCoV Vaccine mRNA-1273 - Abstract
Following the emergency use authorization of the vaccine mRNA-1273 on 18th December 2020 in the US and the vaccine BNT162b2 one week earlier, two mRNA vaccines are in currently used for the prevention of coronavirus disease 2019 (COVID-19). Phase 3 pivotal trials on both vaccines excluded individuals with a history of allergy to vaccine components. Immediately after the initiation of vaccination in the United Kingdom, Canada, and in the US, anaphylactic reactions have been reported. While the culprit trigger requires investigation, initial reports suggested the excipient polyethylene glycol 2000 (PEG-2000), which is contained in both vaccines as PEG-micellar carrier system as the potential culprit. Surface PEG chains form a hydrate shell to increase stability and prevent opsonization. Allergic reactions to such PEG-ylated lipids are rarely IgE-mediated, but may result from complement activation-related pseudoallergy (CARPA) that has been described to similar liposomes. In addition, mRNA-1273 also contains tromethamine (trometamol), which has been reported to cause anaphylaxis to e.g. gadolinium-based or iodinated contrast media. Skin prick-, intradermal-, epicutaneous- tests, in vitro sIgE assessment, evaluation of sIgG/IgM, as well as basophil activation test are in use to demonstrate allergic reactions to various components of the vaccines.
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- 2021
79. Marked Increase in Avidity of SARS-CoV-2 Antibodies 7–8 Months After Infection Is Not Diminished in Old Age
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Annika Rössler, Verena Fleischer, Dorothee von Laer, Reinhard Würzner, Janine Kimpel, Wegene Borena, Lydia Riepler, Matthias Baumgartner, Katie Bates, Daniel Pichler, University of Zurich, and Würzner, Reinhard
- Subjects
Adult ,Male ,0301 basic medicine ,Adolescent ,Enzyme-Linked Immunosorbent Assay ,610 Medicine & health ,chemical and pharmacologic phenomena ,urea ,Antibodies, Viral ,antibody avidity ,Neutralization ,Immunoglobulin G ,Cohort Studies ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,neutralization assay ,Major Article ,Humans ,Immunology and Allergy ,Medicine ,Avidity ,Respiratory system ,Young adult ,Aged ,biology ,SARS-CoV-2 ,business.industry ,COVID-19 ,2725 Infectious Diseases ,Middle Aged ,Antibodies, Neutralizing ,AcademicSubjects/MED00290 ,030104 developmental biology ,Infectious Diseases ,10036 Medical Clinic ,Austria ,Immunology ,Cohort ,2723 Immunology and Allergy ,biology.protein ,Female ,Antibody ,business ,030217 neurology & neurosurgery - Abstract
The kinetics of immunoglobulin G (IgG) avidity maturation during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection obtained from 217 participants of the Ischgl cohort, Austria, was studied 0.5–1.5 months (baseline) and 7–8 months (follow-up) after infection. The IgG avidity assay, using a modified IgG enzyme-linked immunosorbent assay (ELISA) and 5.5 M urea, revealed that old age does not diminish the increase in avidity, detected in all participants positive at both time points, from 18% to 42%. High avidity was associated with a marked residual neutralization capacity in 97.2.% of participants (211/217), which was even higher in the older age group, revealing an important role of avidity assays as easy and cheap surrogate tests for assessing the maturation of the immune system conveying potential protection against further SARS-CoV-2 infections without necessitating expensive and laborious neutralization assays.
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- 2021
80. Thermal conditioning improves quality and speed of keratinocyte sheet production for burn wound treatment
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Maurizio Calcagni, Laura Frese, Pietro Giovanoli, Simon P. Hoerstrup, Brigitte von Rechenberg, Salim E Darwiche, University of Zurich, and Frese, Laura
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Keratinocytes ,0301 basic medicine ,2716 Genetics (clinical) ,Cancer Research ,2747 Transplantation ,Cellular differentiation ,Immunology ,Human keratinocyte ,610 Medicine & health ,1307 Cell Biology ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,Time windows ,medicine ,Humans ,Immunology and Allergy ,1306 Cancer Research ,Severe burn ,10266 Clinic for Reconstructive Surgery ,Cells, Cultured ,Genetics (clinical) ,Skin ,Wound Healing ,2403 Immunology ,Transplantation ,Burn wound ,business.industry ,Cell Differentiation ,Skin Transplantation ,11359 Institute for Regenerative Medicine (IREM) ,Cell Biology ,Thermal conditioning ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,2723 Immunology and Allergy ,2730 Oncology ,Burns ,Keratinocyte ,business - Abstract
Background aims Cultured patient-specific keratinocyte sheets have been used clinically since the 1970s for the treatment of large severe burns. However, despite significant developments in recent years, successful and sustainable treatment is still a challenge. Reliable, high-quality grafts with faster availability and a flexible time window for transplantation are required to improve clinical outcomes. Methods Keratinocytes are usually grown in vitro at 37°C. Given the large temperature differences in native skin tissue, the aim of the authors’ study was to investigate thermal conditioning of keratinocyte sheet production. Therefore, the influence of 31°C, 33°C and 37°C on cell expansion and differentiation in terms of proliferation and sheet formation efficacy was investigated. In addition, the thermal effect on the biological status and thus the quality of the graft was assessed on the basis of the release of wound healing-related biofactors in various stages of graft development. Results The authors demonstrated that temperature is a decisive factor in the production of human keratinocyte sheets. By using specific temperature ranges, the authors have succeeded in optimizing the individual manufacturing steps. During the cell expansion phase, cultivation at 37°C was most effective. After 6 days of culture at 37°C, three times and six times higher numbers of viable cells were obtained compared with 33°C and 31°C. During the cell differentiation and sheet formation phase, however, the cells benefited from a mildly hypothermic temperature of 33°C. Keratinocytes showed increased differentiation potential and formed better epidermal structures, which led to faster biomechanical sheet stability at day 18. In addition, a cultivation temperature of 33°C resulted in a longer lasting and higher secretion of the investigated immunomodulatory, anti-inflammatory, angiogenic and pro-inflammatory biofactors. Conclusions These results show that by using specific temperature ranges, it is possible to accelerate the large-scale production of cultivated keratinocyte sheets while at the same time improving quality. Cultivated keratinocyte sheets are available as early as 18 days post-biopsy and at any time for 7 days thereafter, which increases the flexibility of the process for surgeons and patients alike. These findings will help to provide better clinical outcomes, with an increased take rate in severe burn patients.
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- 2021
81. ARIA‐EAACI statement on severe allergic reactions to COVID‐19 vaccines – An EAACI‐ARIA Position Paper
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Ioana Agache, Eva Untersmayr, Torsten Zuberbier, Jean Bousquet, Karin Hoffmann-Sommergruber, Mübeccel Akdis, María José Torres, Stefano Del Giacco, Cezmi A. Akdis, G. Walter Canonica, Anna Bedbrook, Ludger Klimek, Marek Jutel, Edward F. Knol, Margitta Worm, Tomas Chivato, Mohamed H. Shamji, Johannes Ring, Jürgen Schwarze, Liam O'Mahony, University of Zurich, and Klimek, Ludger
- Subjects
0301 basic medicine ,Allergy ,medicine.medical_specialty ,COVID-19 Vaccines ,Immunology ,Population ,610 Medicine & health ,Herd immunity ,03 medical and health sciences ,0302 clinical medicine ,10183 Swiss Institute of Allergy and Asthma Research ,medicine ,Humans ,Immunology and Allergy ,Medical history ,education ,Intensive care medicine ,Adverse effect ,BNT162 Vaccine ,Asthma ,Vaccines ,2403 Immunology ,education.field_of_study ,SARS-CoV-2 ,business.industry ,COVID-19 ,medicine.disease ,Vaccination ,030104 developmental biology ,030228 respiratory system ,2723 Immunology and Allergy ,business ,Anaphylaxis - Abstract
Coronavirus disease 2019 (COVID-19) vaccine BNT162b2 received approval and within the first few days of public vaccination several severe anaphylaxis cases occurred. An investigation is taking place to understand the cases and their triggers. The vaccine will be administered to a large number of individuals worldwide and concerns raised for severe adverse events might occur. With the current information, the European Academy of Allergy and Clinical Immunology (EAACI) states its position for the following preliminary recommendations that are to be revised as soon as more data emerges. To minimize the risk of severe allergic reactions in vaccinated individuals, it is urgently required to understand the specific nature of the reported severe allergic reactions, including the background medical history of the individuals affected and the mechanisms involved. To achieve this goal all clinical and laboratory information should be collected and reported. Mild and moderate allergic patients should not be excluded from the vaccine as the exclusion of all these patients from vaccination may have a significant impact on reaching the goal of population immunity. Health care practitioners vaccinating against COVID-19 are required to be sufficiently prepared to recognise and treat anaphylaxis properly with the ability to administer adrenaline. A mandatory observation period after vaccine administration of at least 15 minutes for all individuals should be followed. The current data has not shown any higher risk for patients suffering from allergic rhinitis or asthma and this message should be clearly stated by physicians to give our patients trust. The benefit of the vaccination clearly outweighs the risk of severe COVID-19 development including the more than 30% of the population suffering from allergic diseases.
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- 2021
82. Intestinal eosinophils, homeostasis and response to bacterial intrusion
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Alessandra Gurtner, Isabelle C. Arnold, Ignacio Gonzalez-Perez, University of Zurich, and Arnold, Isabelle C
- Subjects
Intestinal homeostasis ,0301 basic medicine ,Protective immunity ,medicine.medical_treatment ,Immunology ,610 Medicine & health ,Review ,Biology ,10263 Institute of Experimental Immunology ,IFN-gamma ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Bacterial infections ,medicine ,Extracellular DNA traps ,Homeostasis ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,Intestinal Mucosa ,Tissue homeostasis ,Inflammation ,2403 Immunology ,Lamina propria ,Effector ,Microbiota ,IBDs ,Epithelium ,Cell biology ,Eosinophils ,Intestines ,030104 developmental biology ,Cytokine ,medicine.anatomical_structure ,2723 Immunology and Allergy ,570 Life sciences ,biology ,Cytokines ,030215 immunology - Abstract
Eosinophils are traditionally considered as end-stage effector cells involved in the pathogenesis of Th2 immune-mediated disorders as well as in the protection against parasite infection. However, this restricted view has recently been challenged by a series of studies revealing the highly plastic nature of these cells and implication in various homeostatic processes. Large numbers of eosinophils reside in the lamina propria of the gastrointestinal tract, at the front line of host defence, where they contribute to maintain the intestinal epithelial barrier function in the face of inflammation-associated epithelial cell damage. Eosinophils confer active protection against bacterial pathogens capable of penetrating the mucosal barrier through the release of cytotoxic compounds and the generation of extracellular DNA traps. Eosinophils also integrate tissue-specific cytokine signals such as IFN-γ, which synergise with bacterial recognition pathways to enforce different context-dependent functional responses, thereby ensuring a rapid adaptation to the ever-changing intestinal environment. The ability of eosinophils to regulate local immune responses and respond to microbial stimuli further supports the pivotal role of these cells in the maintenance of tissue homeostasis at the intestinal interface.
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- 2021
83. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions?
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Akdis, Cezmi A, University of Zurich, and Akdis, Cezmi A
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0301 basic medicine ,2403 Immunology ,Allergy ,business.industry ,610 Medicine & health ,General Medicine ,Autoimmune hepatitis ,Disease ,medicine.disease ,medicine.disease_cause ,Coeliac disease ,Autoimmunity ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,10183 Swiss Institute of Allergy and Asthma Research ,Immunology ,2723 Immunology and Allergy ,medicine ,Microbiome ,Eosinophilic esophagitis ,business ,Tissue homeostasis ,030215 immunology - Abstract
There has been a steep increase in allergic and autoimmune diseases, reaching epidemic proportions and now affecting more than one billion people worldwide. These diseases are more common in industrialized countries, and their prevalence continues to rise in developing countries in parallel to urbanization and industrialization. Intact skin and mucosal barriers are crucial for the maintenance of tissue homeostasis as they protect host tissues from infections, environmental toxins, pollutants and allergens. A defective epithelial barrier has been demonstrated in allergic and autoimmune conditions such as asthma, atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, coeliac disease and inflammatory bowel disease. In addition, leakiness of the gut epithelium is also implicated in systemic autoimmune and metabolic conditions such as diabetes, obesity, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and autoimmune hepatitis. Finally, distant inflammatory responses due to a ‘leaky gut’ and microbiome changes are suspected in Alzheimer disease, Parkinson disease, chronic depression and autism spectrum disorders. This article introduces an extended ‘epithelial barrier hypothesis’, which proposes that the increase in epithelial barrier-damaging agents linked to industrialization, urbanization and modern life underlies the rise in allergic, autoimmune and other chronic conditions. Furthermore, it discusses how the immune responses to dysbiotic microbiota that cross the damaged barrier may be involved in the development of these diseases. In this review, Cezmi Akdis discusses how epithelial barrier-damaging agents linked to industrialization, urbanization and modern life may explain the increased prevalence of allergic disease as well as a wide range of autoimmune and metabolic conditions in which immune responses to translocated bacteria have systemic effects.
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- 2021
84. Prediction of histology by B-mode and PD-mode ultrasound across different joint locations and diseases
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Micheroli, Raphael, Pauli, Chantal, Bürki, Kristina, Rossbach, Philipp, Distler, Oliver, Ospelt, Caroline, Ciurea, Adrian, University of Zurich, and Micheroli, Raphael
- Subjects
2403 Immunology ,Rheumatology ,10049 Institute of Pathology and Molecular Pathology ,2745 Rheumatology ,Immunology ,10051 Rheumatology Clinic and Institute of Physical Medicine ,2723 Immunology and Allergy ,Immunology and Allergy ,Humans ,610 Medicine & health ,Joints ,Ultrasonography - Published
- 2022
85. Impact of Latent Tuberculosis on Diabetes
- Author
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Tepekule, Burcu, Kusejko, Katharina, Zeeb, Marius, Tarr, Philip E, Calmy, Alexandra, Battegay, Manuel, Furrer, Hansjakob, Cavassini, Matthias, Bernasconi, Enos, Notter, Julia, Günthard, Huldrych F, Nemeth, Johannes, Kouyos, Roger D, University of Zurich, and Tepekule, Burcu
- Subjects
10028 Institute of Medical Virology ,10234 Clinic for Infectious Diseases ,2723 Immunology and Allergy ,610 Medicine & health ,2725 Infectious Diseases - Published
- 2022
86. Effects of diet on the outcomes of rheumatic and musculoskeletal diseases (RMDs): systematic review and meta-analyses informing the 2021 EULAR recommendations for lifestyle improvements in people with RMDs
- Author
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James M Gwinnutt, Maud Wieczorek, Javier Rodríguez-Carrio, Andra Balanescu, Heike A Bischoff-Ferrari, Annelies Boonen, Giulio Cavalli, Savia de Souza, Annette de Thurah, Thomas E Dorner, Rikke Helene Moe, Polina Putrik, Lucía Silva-Fernández, Tanja Stamm, Karen Walker-Bone, Joep Welling, Mirjana Zlatković-Švenda, Francis Guillemin, Suzanne M M Verstappen, University of Zurich, and Verstappen, Suzanne M M
- Subjects
ARTHRITIS PATIENTS ,11221 Department of Aging Medicine ,2745 Rheumatology ,Immunology ,Musculoskeletal Diseases/epidemiology ,610 Medicine & health ,PLACEBO-CONTROLLED TRIAL ,RANDOMIZED DOUBLE-BLIND ,Arthritis, Rheumatoid ,Muscular Diseases ,Rheumatology ,QUALITY-OF-LIFE ,Rheumatoid ,Rheumatic Diseases ,Osteoarthritis ,LUPUS-ERYTHEMATOSUS ,Humans ,Immunology and Allergy ,KNEE OSTEOARTHRITIS DATA ,VITAMIN-D SUPPLEMENTATION ,Musculoskeletal Diseases ,Life Style ,POLYUNSATURATED FATTY-ACIDS ,2403 Immunology ,Arthritis ,MEDITERRANEAN-TYPE DIET ,Diet ,arthritis ,patient reported outcome measures ,2723 Immunology and Allergy ,Osteoarthritis/epidemiology ,Rheumatic Diseases/epidemiology ,epidemiology ,FISH OIL SUPPLEMENTATION - Abstract
BackgroundA EULAR taskforce was convened to develop recommendations for lifestyle behaviours in rheumatic and musculoskeletal diseases (RMDs). In this paper, the literature on the effect of diet on the progression of RMDs is reviewed.MethodsSystematic reviews and meta-analyses were performed of studies related to diet and disease outcomes in seven RMDs: osteoarthritis (OA), rheumatoid arthritis (RA), systemic lupus erythematosus, axial spondyloarthritis, psoriatic arthritis, systemic sclerosis and gout. In the first phase, existing relevant systematic reviews and meta-analyses, published from 2013 to 2018, were identified. In the second phase, the review was expanded to include published original studies on diet in RMDs, with no restriction on publication date. Systematic reviews or original studies were included if they assessed a dietary exposure in one of the above RMDs, and reported results regarding progression of disease (eg, pain, function, joint damage).ResultsIn total, 24 systematic reviews and 150 original articles were included. Many dietary exposures have been studied (n=83), although the majority of studies addressed people with OA and RA. Most dietary exposures were assessed by relatively few studies. Exposures that have been assessed by multiple, well conducted studies (eg, OA: vitamin D, chondroitin, glucosamine; RA: omega-3) were classified as moderate evidence of small effects on disease progression.ConclusionThe current literature suggests that there is moderate evidence for a small benefit for certain dietary components. High-level evidence of clinically meaningful effect sizes from individual dietary exposures on outcomes in RMDs is missing.
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- 2022
87. Immune Alterations in a Patient With Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome: A Case Report
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Silvera-Ruiz, Silene M, Gemperle, Corinne, Peano, Natalia, Olivero, Valentina, Becerra, Adriana, Häberle, Johannes, Gruppi, Adriana, Laróvere, Laura E, Motrich, Ruben D, University of Zurich, and Motrich, Ruben D
- Subjects
2403 Immunology ,10036 Medical Clinic ,Immunology ,2723 Immunology and Allergy ,Immunology and Allergy ,610 Medicine & health - Abstract
The hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive inborn error of the urea cycle caused by mutations in the SLC25A15 gene. Besides the well-known metabolic complications, patients often present intercurrent infections associated with acute hyperammonemia and metabolic decompensation. However, it is currently unknown whether intercurrent infections are associated with immunological alterations besides the known metabolic imbalances. Herein, we describe the case of a 3-years-old girl affected by the HHH syndrome caused by two novel SLC25A15 gene mutations associated with immune phenotypic and functional alterations. She was admitted to the hospital with an episode of recurrent otitis, somnolence, confusion, and lethargy. Laboratory tests revealed severe hyperammonemia, elevated serum levels of liver transaminases, hemostasis alterations, hyperglutaminemia and strikingly increased orotic aciduria. Noteworthy, serum protein electrophoresis showed a reduction in the gamma globulin fraction. Direct sequencing of the SLC25A15 gene revealed two heterozygous non-conservative substitutions in the exon 5: c.649G>A (p.Gly217Arg) and c.706A>G (p.Arg236Gly). In silico analysis indicated that both mutations significantly impair protein structure and function and are consistent with the patient clinical status confirming the diagnosis of HHH syndrome. In addition, the immune analysis revealed reduced levels of serum IgG and striking phenotypic and functional alterations in the T and B cell immune compartments. Our study has identified two non-previously described mutations in the SLC25A15 gene underlying the HHH syndrome. Moreover, we are reporting for the first time functional and phenotypic immunologic alterations in this rare inborn error of metabolism that would render the patient immunocompromised and might be related to the high frequency of intercurrent infections observed in patients bearing urea cycle disorders. Our results point out the importance of a comprehensive analysis to gain further insights into the underlying pathophysiology of the disease that would allow better patient care and quality of life.
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- 2022
88. PIRCHE-II scores prove useful as a predictive biomarker among kidney transplant recipients with rejection: An analysis of indication and follow-up biopsies
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Tahm Spitznagel, Laurenz S. Matter, Yves L. Kaufmann, Jakob Nilsson, Seraina von Moos, Thomas Schachtner, University of Zurich, and Schachtner, Thomas
- Subjects
2403 Immunology ,Biopsy ,Histocompatibility Testing ,Immunology ,610 Medicine & health ,Kidney Transplantation ,Antibodies ,Epitopes ,HLA Antigens ,Histocompatibility Antigens ,10033 Clinic for Immunology ,2723 Immunology and Allergy ,Immunology and Allergy ,Biomarkers ,Follow-Up Studies - Abstract
BackgroundIndication biopsies for deterioration of kidney allograft function often require follow-up biopsies to assess treatment response or lack of improvement. Immune-mediated injury, namely borderline rejection (BLR), T-cell mediated rejection (TCMR), or antibody-mediated rejection (ABMR), results from preformed or de novo alloreactivity due to donor and recipient HLA-mismatches. The impact of HLA-mismatches on alloreactivity is determined by highly immunogenic HLA-epitopes.MethodsWe analyzed 123 kidney transplant recipients (KTRs) from 2009 to 2019 who underwent a first indication and a follow-up biopsy. KTRs were divided into three groups according to the first biopsy: No rejection (NR)/BLR (n=68); TCMR (n=21); ABMR (n=34). The HLA-derived epitope-mismatches were calculated using the Predicted Indirectly Recognizable HLA-Epitopes (PIRCHE-II) algorithm.ResultsGroup NR/BLR: KTRs with higher total PIRCHE-II scores were more likely to develop TCMR in the follow-up biopsy (p=0.031). Interestingly, these differences were significant for both HLA-class I- (p=0.017) and HLA-class II-derived (p=0.017) PIRCHE-II scores. Group TCMR: KTRs with ongoing TCMR in the follow-up biopsy were more likely to show higher total PIRCHE-II scores (median 101.50 vs. 74.00). Group ABMR: KTRs with higher total PIRCHE-II scores were more likely to show an increase in the microvascular inflammation score in the follow-up biopsy. This difference was more pronounced for the HLA-class II-derived PIRCHE-II scores (median 70.00 vs. 31.76; p=0.086).ConclusionsPIRCHE-II scores may prove useful as a biomarker to predict the histopathological changes of immune-related injury from a first indication to a follow-up biopsy. This immunological risk stratification may contribute to individualized treatment strategies.
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- 2022
89. Type 2 immune predisposition results in accelerated neutrophil aging causing susceptibility to bacterial infection
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Egholm, Cecilie, Özcan, Alaz, Breu, Daniel, Boyman, Onur, University of Zurich, and Boyman, Onur
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Hypersensitivity, Immediate ,2403 Immunology ,Aging ,Neutrophils ,Immunology ,610 Medicine & health ,Bacterial Infections ,General Medicine ,Mice ,Phagocytosis ,10033 Clinic for Immunology ,2723 Immunology and Allergy ,Animals ,Interleukin-4 - Abstract
Atopic individuals show enhanced type 2 immune cell responses and a susceptibility to infections with certain bacteria and viruses. Although patients with allergic diseases harbor normal counts of circulating neutrophils, these cells exert deficient effector functions. However, the underlying mechanism of this dysregulation of neutrophils remains ill defined. Here, we find that development, aging, and elimination of neutrophils are accelerated in mice with a predisposition to type 2 immunity, which, in turn, causes susceptibility to infection with several bacteria. Neutrophil-mediated immunity to bacterial infection was greatly decreased in mice with a genetic or induced bias to type 2 immunity. Abrogation of interleukin-4 (IL-4) receptor signaling in these animals fully restored their antibacterial defense, which largely depended on Ly6G+neutrophils. IL-4 signals accelerated the maturation of neutrophils in the bone marrow and caused their rapid release to the circulation and periphery. IL-4–stimulated neutrophils aged more rapidly in the periphery, as evidenced by their phenotypic and functional changes, including their decreased phagocytosis of bacterial particles. Moreover, neutrophils from type 2 immune predisposed mice were eliminated at a higher rate by apoptosis and phagocytosis by macrophages and dendritic cells. Collectively, IL-4 signaling–mediated neutrophil aging constitutes an important adaptive deficiency in type 2 inflammation, contributing to recurrent bacterial infections.
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- 2022
90. Human Melanoma-Associated Mast Cells Display a Distinct Transcriptional Signature Characterized by an Upregulation of the Complement Component 3 That Correlates With Poor Prognosis
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Bahri, Rajia, Kiss, Orsolya, Prise, Ian, Garcia-Rodriguez, Karen M, Atmoko, Haris, Martínez-Gómez, Julia M, Levesque, Mitchell Paul, Dummer, Reinhard, Smith, Michael P, Wellbrock, Claudia, Bulfone-Paus, Silvia, University of Zurich, and Bulfone-Paus, Silvia
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2403 Immunology ,Skin Neoplasms ,Immunology ,10177 Dermatology Clinic ,610 Medicine & health ,Complement C3 ,Up-Regulation ,Transforming Growth Factor beta ,2723 Immunology and Allergy ,Tumor Microenvironment ,Humans ,Immunology and Allergy ,Mast Cells ,Melanoma ,Peptide Hydrolases - Abstract
Cutaneous melanoma is one of the most aggressive human malignancies and shows increasing incidence. Mast cells (MCs), long-lived tissue-resident cells that are particularly abundant in human skin where they regulate both innate and adaptive immunity, are associated with melanoma stroma (MAMCs). Thus, MAMCs could impact melanoma development, progression, and metastasis by secreting proteases, pro-angiogenic factors, and both pro-inflammatory and immuno-inhibitory mediators. To interrogate the as-yet poorly characterized role of human MAMCs, we have purified MCs from melanoma skin biopsies and performed RNA-seq analysis. Here, we demonstrate that MAMCs display a unique transcriptome signature defined by the downregulation of the FcεRI signaling pathway, a distinct expression pattern of proteases and pro-angiogenic factors, and a profound upregulation of complement component C3. Furthermore, in melanoma tissue, we observe a significantly increased number of C3+ MCs in stage IV melanoma. Moreover, in patients, C3 expression significantly correlates with the MC-specific marker TPSAB1, and the high expression of both markers is linked with poorer melanoma survival. In vitro, we show that melanoma cell supernatants and tumor microenvironment (TME) mediators such as TGF-β, IL-33, and IL-1β induce some of the changes found in MAMCs and significantly modulate C3 expression and activity in MCs. Taken together, these data suggest that melanoma-secreted cytokines such as TGF-β and IL-1β contribute to the melanoma microenvironment by upregulating C3 expression in MAMCs, thus inducing an MC phenotype switch that negatively impacts melanoma prognosis.
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- 2022
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91. Proteomic Characterization of the Oral Pathogen Filifactor alocis Reveals Key Inter-Protein Interactions of Its RTX Toxin: FtxA
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Bao, Kai, Claesson, Rolf, Gehrig, Peter, Grossmann, Jonas, Oscarsson, Jan, Belibasakis, Georgios N, University of Zurich, Bao, Kai, and Belibasakis, Georgios N
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Microbiology (medical) ,General Immunology and Microbiology ,Filifactor alocis ,label-free quantification proteomics ,FtxA ,610 Medicine & health ,10071 Functional Genomics Center Zurich ,2725 Infectious Diseases ,2726 Microbiology (medical) ,Infectious Diseases ,2400 General Immunology and Microbiology ,2723 Immunology and Allergy ,1312 Molecular Biology ,570 Life sciences ,biology ,Immunology and Allergy ,Molecular Biology - Abstract
Filifactor alocis is a Gram-positive asaccharolytic, obligate anaerobic rod that has been isolated from a variety of oral infections including periodontitis, peri-implantitis, and odontogenic abscesses. As a newly emerging pathogen, its type strain has been investigated for pathogenic properties, yet little is known about its virulence variations among strains. We previously screened the whole genome of nine clinical oral isolates and a reference strain of F. alocis, and they expressed a novel RTX toxin, FtxA. In the present study, we aimed to use label-free quantification proteomics to characterize the full proteome of those ten F. alocis strains. A total of 872 proteins were quantified, and 97 among them were differentially expressed in FtxA-positive strains compared with the negative strains. In addition, 44 of these differentially expressed proteins formed 66 pairs of associations based on their predicted functions, which included clusters of proteins with DNA repair/mediated transformation and catalytic activity-related function, indicating different biosynthetic activities among strains. FtxA displayed specific interactions with another six intracellular proteins, forming a functional cluster that could discriminate between FtxA-producing and non-producing strains. Among them were FtxB and FtxD, predicted to be encoded by the same operon as FtxA. While revealing the broader qualitative and quantitative proteomic landscape of F. alocis, this study also sheds light on the deeper functional inter-relationships of FtxA, thus placing this RTX family member into context as a major virulence factor of this species., Pathogens, 11 (5), ISSN:2076-0817
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- 2022
- Full Text
- View/download PDF
92. Development and validation of the Food Allergy Severity Score
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Fernández‐Rivas, Montserrat, Gómez García, Ismael, Gonzalo‐Fernández, Alejandro, Fuentes Ferrer, Manuel, Dölle‐Bierke, Sabine, Marco‐Martín, Guadalupe, Ballmer-Weber, Barbara K, et al, University of Zurich, and Fernández‐Rivas, Montserrat
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2403 Immunology ,Immunology ,2723 Immunology and Allergy ,10177 Dermatology Clinic ,Immunology and Allergy ,610 Medicine & health - Published
- 2022
93. Is the epithelial barrier hypothesis the key to understanding the higher incidence and excess mortality during COVID-19 pandemic? The case of Northern Italy
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Silvana Fiorito, Marzia Soligo, Yadong Gao, Ismail Ogulur, Cezmi A. Akdis, Sergio Bonini, University of Zurich, and Fiorito, Silvana
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Air Pollutants ,2403 Immunology ,SARS-CoV-2 ,Incidence ,Immunology ,COVID-19 ,610 Medicine & health ,Italy ,10183 Swiss Institute of Allergy and Asthma Research ,Air Pollution ,2723 Immunology and Allergy ,Humans ,Immunology and Allergy ,Particulate Matter ,Pandemics - Abstract
The high incidence and increased mortality of COVID-19 make Italy among the most impacted countries by SARS-CoV-2 outbreak. In the beginning of the pandemic, Northern regions accounted for 40% of cases and 45% of deaths from COVID-19 in Italy. Several factors have been suggested to explain the higher incidence and excess mortality from COVID-19 in these regions. It is noticed that Northern Italian regions, and particularly the cities in Po Valley, are the areas with the highest air pollution due to commercial vehicle traffic, industry and a stagnant meteorological condition, with one of the highest levels in Italy and Europe of fine particulate matter 2.5 micron or smaller in size (PM2.5). PM2.5, the major environmental pollutant deriving mainly by factory and automobile exhaust emissions and coal combustion, increases the expression of angiotensin-converting enzyme 2, the epithelial cell entry receptor for SARS-CoV-2, and thus increase the susceptibility to this virus. The epithelial barrier hypothesis proposes that many diverse diseases may rise from the disruption of epithelial barrier of skin, respiratory tract and gastrointestinal system, including allergic diseases, metabolic and autoimmune diseases, and chronic neuropsychiatric conditions. There is evidence of a close correlation between air pollution and airway epithelial barrier dysfunction. Air pollution, causing lung epithelial barrier dysfunction, may contribute to local chronic inflammation, microbiome dysbiosis and impaired antiviral immune response against SARS-CoV-2, all of which contribute to the high incidence and excess mortality from COVID-19. In addition, air pollution and epithelial barrier dysfunction contribute also to the higher prevalence of several comorbidities of COVID-19, such as diabetes, chronic obstructive pulmonary disease and obesity, which have been identified as risk factors for mortality of COVID-19. In this article, on the basis of epidemiological and environmental monitoring data in Northern Italy, it is suggested that epithelial barrier hypothesis may help to understand the excess burden and mortality from COVID-19.
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- 2022
94. Nutrient supplementation for prevention of viral respiratory tract infections in healthy subjects: A systematic review and meta‐analysis
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Carina Venter, Berber Vlieg-Boerstra, Kate Grimshaw, Milena Sokolowska, Hanneke Oude Elberink, Marloes van Splunter, Rosan Meyer, Liam O'Mahony, Carlo Agostoni, Nicolette W. de Jong, Isabella Pali-Schöll, Mari Sasaki, Caroline Roduit, Eva Untersmayr, Isabel Skypala, Valentina De Cosmi, Antonella Muraro, Gregorio P. Milani, Bright I Nwaru, University of Zurich, and Vlieg‐Boerstra, Berber
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Vitamin ,Adult ,PRESCHOOL-CHILDREN ,COMMON COLD ,Population ,Immunology ,Physiology ,610 Medicine & health ,chemistry.chemical_compound ,VITAMIN-A SUPPLEMENTATION ,DOUBLE-BLIND ,PLASMA RETINOL LEVEL ,nutrients ,10183 Swiss Institute of Allergy and Asthma Research ,Vitamin D and neurology ,medicine ,Humans ,Immunology and Allergy ,Vitamin B12 ,Vitamin D ,education ,Child ,Respiratory Tract Infections ,education.field_of_study ,2403 Immunology ,Respiratory tract infections ,business.industry ,SARS-CoV-2 ,Incidence (epidemiology) ,COVID-19 ,Common cold ,NURSING-HOME RESIDENTS ,acute respiratory tract infection ,RANDOMIZED CONTROLLED-TRIAL ,Micronutrient ,medicine.disease ,Healthy Volunteers ,ZINC SUPPLEMENTATION ,Zinc ,chemistry ,Dietary Supplements ,supplementation ,SEASONAL INFLUENZA-A ,2723 Immunology and Allergy ,business ,BETA-CAROTENE SUPPLEMENTATION - Abstract
It remains uncertain as to whether nutrient supplementation for the general population considered healthy could be useful in the prevention of RTIs, such as COVID-19. In this systematic review and meta-analysis, the evidence was evaluated for primary prevention of any viral respiratory tract infection (RTI) such as SARS-CoV-2, through supplementation of nutrients with a recognized role in immune function: multiple micronutrients, vitamin A, folic acid, vitamin B12, C, D, E, beta-carotene, zinc, iron and long-chain polyunsaturated fatty acids. The search produced 15,163 records of which 93 papers (based on 115 studies) met the inclusion criteria, resulting in 199,055 subjects (191,636 children and 7,419 adults) from 37 countries. Sixty-three studies were included in the meta-analyses, which was performed for children and adults separately. By stratifying the meta-analysis by world regions, only studies performed in Asia showed a significant but heterogeneous protective effect of zinc supplementation on RTIs (RR 0.86, 95% CI 0.7-0.96, I2 = 79.1%, p = .000). Vitamin D supplementation in adults significantly decreased the incidence of RTI (RR 0.89, 95% CI 0.79-0.99, p = .272), particularly in North America (RR 0.82 95% CI 0.68-0.97), but not in Europe or Oceania. Supplementation of nutrients in the general population has either no or at most a very limited effect on prevention of RTIs. Zinc supplementation appears protective for children in Asia, whilst vitamin D may protect adults in the USA and Canada. In 10/115 (8.7%) studies post-hoc analyses based on stratification for nutritional status was performed. In only one study zinc supplementation was found to be more effective in children with low zinc serum as compared to children with normal zinc serum levels.
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- 2022
95. Antibody Response to SARS-CoV-2 Vaccination in Patients following Allogeneic Hematopoietic Cell Transplantation
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Huang, Alice, Cicin-Sain, Caroline, Pasin, Chloé, Epp, Selina, Audigé, Annette, Müller, Nicolas J, Nilsson, Jakob, Bankova, Andriyana, Wolfensberger, Nathan, Vilinovszki, Oliver, Nair, Gayathri, Hockl, Philipp, Schanz, Urs, Kouyos, Roger D, Hasse, Barbara, Zinkernagel, Annelies S, Trkola, Alexandra, Manz, Markus G, Abela, Irene A, Müller, Antonia M S, University of Zurich, and Müller, Antonia M S
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10028 Institute of Medical Virology ,COVID-19 Vaccines ,2747 Transplantation ,2720 Hematology ,610 Medicine & health ,2700 General Medicine ,Article ,10234 Clinic for Infectious Diseases ,1307 Cell Biology ,Immunology and Allergy ,Humans ,BNT162 Vaccine ,Aged ,Transplantation ,SARS-CoV-2 ,Vaccination ,Hematopoietic Stem Cell Transplantation ,COVID-19 ,Cell Biology ,Hematology ,surgical procedures, operative ,1313 Molecular Medicine ,Antibody Formation ,10032 Clinic for Oncology and Hematology ,2723 Immunology and Allergy ,Molecular Medicine - Abstract
Background Vaccines against SARS-CoV-2 have been rapidly approved. While pivotal studies were conducted in healthy volunteers, little information is available on safety and efficacy of mRNA vaccines in immunocompromised patients, including recipients of allogeneic hematopoietic cell transplantations (allo-HCT). Objectives Here, we used a novel assay to analyze patient- and transplant-related factors and their influence on immune responses over an extended period of time (up to 6 months) to the SARS-CoV-2 vaccination in a large and homogenous group of allo-HCT recipients at a single center in Switzerland. Study Design We examined longitudinal antibody responses to SARS-CoV-2 vaccination with BNT162b2 (BioNTech/Pfizer) or mRNA-1273 (Moderna) in 110 allo-HCT recipients and 86 healthy controls. Seroprofiling recording IgG, IgA, and IgM reactivities against SARS-CoV-2 antigens (receptor-binding domain (RBD), spike glycoprotein subunits S1 and S2, and nucleocapsid protein (N)) was performed prior to vaccination, prior to the 2nd dose, and 1, 3, and 6 months (m) after the 2nd dose. Patients were stratified to three groups (A) 3-6m post HCT; (B) 6-12m post HCT; and (C) >12m post HCT. Results Individuals early post allo-HCT (3-6 and 6-12m post HCT) developed significantly lower antibody titers after vaccination compared to patients >12m post allo-HCT and healthy controls (p65 years (p=0.030), those under immunosuppression for prevention or treatment of graft-vs-host disease (GVHD) (p=0.033), and/or with relapsed disease (p=0.014) displayed poor humoral immune response to the vaccine. In contrast, the intensity of the conditioning regimen, underlying disease (myeloid/lymphoid/other), and presence of chronic GVHD had no impact on antibody levels. Antibody titers achieved the highest levels 1m after the 2nd dose of the vaccine but substantially waned in all transplanted groups and healthy controls over time. Conclusions This analysis of long-term vaccine antibody response is of critical importance to allo-HCT recipients and transplant physicians to guide treatment decisions regarding re-vaccination and social behavior during the SARS-CoV-2 pandemic., Graphical Abstract Image, graphical abstract
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- 2022
96. The Role of Defective Epithelial Barriers in Allergic Lung Disease and Asthma Development
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Maciej Chalubinski, Paulina Wawrzyniak, Nazek Noureddine, University of Zurich, and Wawrzyniak, Paulina
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Pulmonary and Respiratory Medicine ,10036 Medical Clinic ,2740 Pulmonary and Respiratory Medicine ,Journal of Asthma and Allergy ,2723 Immunology and Allergy ,Immunology and Allergy ,610 Medicine & health - Abstract
Nazek Noureddine,1â 3 Maciej Chalubinski,4 Paulina Wawrzyniak1,2 1Division of Clinical Chemistry and Biochemistry, University Childrenâs Hospital Zurich, Zurich, Switzerland; 2Childrenâs Research Center, University Childrenâs Hospital Zurich, Zurich, Switzerland; 3Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland; 4Department of Immunology and Allergy, Medical University of Lodz, Lodz, PolandCorrespondence: Paulina Wawrzyniak, Division of Clinical Chemistry and Biochemistry, University Childrenâs Hospital Zurich, Zurich, 8032, Switzerland, Tel +41 44 266 75 42, Email paulina.wawrzyniak@uzh.ch; paulina.wawrzyniak@kispi.uzh.chAbstract: The respiratory epithelium constitutes the physical barrier between the human body and the environment, thus providing functional and immunological protection. It is often exposed to allergens, microbial substances, pathogens, pollutants, and environmental toxins, which lead to dysregulation of the epithelial barrier and result in the chronic inflammation seen in allergic diseases and asthma. This epithelial barrier dysfunction results from the disturbed tight junction formation, which are multi-protein subunits that promote cellâcell adhesion and barrier integrity. The increasing interest and evidence of the role of impaired epithelial barrier function in allergy and asthma highlight the need for innovative approaches that can provide new knowledge in this area. Here, we review and discuss the current role and mechanism of epithelial barrier dysfunction in developing allergic diseases and the effect of current allergy therapies on epithelial barrier restoration.Keywords: bronchial epithelial cells, asthma, allergy, tight junction, inflammation
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- 2022
97. Association between the magnitude of intravenous busulfan exposure and development of hepatic veno-occlusive disease in children and young adults undergoing myeloablative allogeneic hematopoietic cell transplantation
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Bognàr, Tim, Bartelink, Imke H, Egberts, Toine C G, Rademaker, Carin M A, Versluys, A Birgitta, et al, Güngör, Tayfun, University of Zurich, and Bognàr, Tim
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1307 Cell Biology ,10036 Medical Clinic ,2747 Transplantation ,1313 Molecular Medicine ,2720 Hematology ,2723 Immunology and Allergy ,610 Medicine & health - Published
- 2022
98. Tissue-resident memory Th17 cells maintain stable fungal commensalism in the oral mucosa
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Florian R. Kirchner, Salomé LeibundGut-Landmann, University of Zurich, and LeibundGut-Landmann, Salomé
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0301 basic medicine ,Immunology ,Biology ,10263 Institute of Experimental Immunology ,Article ,Microbiology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Antigens, CD ,Candida albicans ,medicine ,Animals ,Homeostasis ,Immunology and Allergy ,Central function ,Oral mucosa ,Symbiosis ,Mice, Knockout ,2403 Immunology ,Host (biology) ,Microbiota ,Interleukin-17 ,Candidiasis ,Fungi ,Mouth Mucosa ,Receptors, Interleukin ,Commensalism ,Corpus albicans ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Organ Specificity ,Murine model ,2723 Immunology and Allergy ,Th17 Cells ,570 Life sciences ,biology ,Immunologic Memory ,Integrin alpha Chains ,10244 Institute of Virology ,030215 immunology - Abstract
Keeping a stable equilibrium between the host and commensal microbes to which we are constantly exposed, poses a major challenge for the immune system. The host mechanisms that regulate homeostasis of the microbiota to prevent infection and inflammatory disorders are not fully understood. Here, we provide evidence that CD4+ tissue-resident memory T (TRM) cells act as central players in this process. Using a murine model of C. albicans commensalism we show that IL-17 producing CD69+CD103+CD4+ memory T cells persist in the colonized tissue long-term and independently of circulatory supplies. Consistent with the requirement of Th17 cells for limiting fungal growth, IL-17-producing TRM cells in the mucosa were sufficient to maintain prolonged colonization, while circulatory T cells were dispensable. Although TRM cells were first proposed to protect from pathogens causing recurrent acute infections, our results support a central function of TRM cells in the maintenance of commensalism.
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- 2021
99. Non‐neutralizing antibodies protect against chronic LCMV infection by promoting infection of inflammatory monocytes in mice
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Fabienne Gräbnitz, Diana Stoycheva, Mariana Borsa, Annette Oxenius, Stefan S. Weber, Ioana Sandu, Ana Amorim, Burkhard Becher, University of Zurich, and Oxenius, Annette
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0301 basic medicine ,viruses ,Priming (immunology) ,CD8-Positive T-Lymphocytes ,10263 Institute of Experimental Immunology ,Antibodies, Viral ,Lymphocyte Activation ,Monocytes ,Mice ,0302 clinical medicine ,Immunopathology ,T-cell activation ,Immunology and Allergy ,Cytotoxic T cell ,Antigens, Ly ,Lymphocytic choriomeningitis virus ,Antigens, Viral ,Research Articles ,Cells, Cultured ,Cellular Senescence ,Disease Resistance ,Mice, Knockout ,biology ,LCMV ,Chronic viral infection ,Inflammatory monocytes ,Non-neutralizing antibodies ,Cell Differentiation ,Acquired immune system ,2723 Immunology and Allergy ,Research Article|Basic ,Antibody ,Immunology ,Immunity to infection ,610 Medicine & health ,Lymphocytic Choriomeningitis ,Lymphocytic choriomeningitis ,Virus ,03 medical and health sciences ,medicine ,Animals ,Humans ,Non‐neutralizing antibodies ,Basic ,Inflammation ,2403 Immunology ,Receptors, IgG ,medicine.disease ,Mice, Inbred C57BL ,Chronic infection ,030104 developmental biology ,T‐cell activation ,Chronic Disease ,biology.protein ,570 Life sciences ,030215 immunology - Abstract
Antibodies play an important role in host defense against microorganisms. Besides direct microbicidal activities, antibodies can also provide indirect protection via crosstalk to constituents of the adaptive immune system. Similar to many human chronic viral infections, persistence of Lymphocytic choriomeningitis virus (LCMV) is associated with compromised T- and B-cell responses. The administration of virus-specific non-neutralizing antibodies (nnAbs) prior to LCMV infection protects against the establishment of chronic infection. Here, we show that LCMV-specific nnAbs bind preferentially Ly6Chi inflammatory monocytes (IMs), promote their infection in an Fc-receptor independent way, and support acquisition of APC properties. By constituting additional T-cell priming opportunities, IMs promote early activation of virus-specific CD8 T cells, eventually tipping the balance between T-cell exhaustion and effector cell differentiation, preventing establishment of viral persistence without causing lethal immunopathology. These results document a beneficial role of IMs in avoiding T-cell exhaustion and an Fc-receptor independent protective mechanism provided by LCMV-specific nnAbs against the establishment of chronic infection., European Journal of Immunology, 51 (6), ISSN:0014-2980, ISSN:1521-4141
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- 2021
100. Real-Life Experience of Monoclonal Antibody Treatments in Chronic Rhinosinusitis with Nasal Polyposis
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Urs C. Steiner, Michael B. Soyka, Peter Schmid-Grendelmeier, Eva C. Meier, University of Zurich, and Soyka, Michael B
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Adult ,Male ,medicine.medical_specialty ,medicine.drug_class ,Immunology ,610 Medicine & health ,Omalizumab ,Monoclonal antibody ,Gastroenterology ,chemistry.chemical_compound ,Nasal Polyps ,Internal medicine ,Anti-Allergic Agents ,medicine ,Humans ,Immunology and Allergy ,Eosinophilia ,Sinusitis ,Interleukin 5 ,Aged ,Retrospective Studies ,Rhinitis ,2403 Immunology ,Eosinophil cationic protein ,business.industry ,Clinical Immunology − Research Article ,10177 Dermatology Clinic ,Antibodies, Monoclonal ,Disease Management ,General Medicine ,Middle Aged ,Benralizumab ,Combined Modality Therapy ,Dupilumab ,Treatment Outcome ,chemistry ,10033 Clinic for Immunology ,2723 Immunology and Allergy ,Female ,Symptom Assessment ,medicine.symptom ,business ,Mepolizumab ,Biomarkers ,medicine.drug - Abstract
Introduction: Few studies assess biologicals such as, omalizumab, mepolizumab, benralizumab, and dupilumab in patients suffering from chronic rhinosinusitis with nasal polyposis (CRSwNP). The reported success rate in these studies differ, and it remains uncertain if there are any biomarkers to predict successful therapy. Our aim was to analyze the therapeutic outcome in a real life setting and to identify predictive biomarkers for successful treatment. Methods: Data from patients with CRSwNP treated with a monoclonal antibody between November 2014 and January 2020 were analyzed retrospectively. Improvement in the polyp score and clinical symptoms like nasal obstruction, sense of smell, nasal discharge, and facial pain were evaluated. Other characteristics, including use of nasal or systemic steroids, comorbidities, previous history of sinus surgery, eosinophilia tissue, blood values (eosinophils, total immunoglobulin E, eosinophilic cationic protein, and interleukin 5), and allergic sensitization in serum were also investigated to identify possible predictive biomarkers. Results: Forty-eight treatments in 29 patients (m/f = 15/14) aged 27–70 years were reviewed. Treatments with mepolizumab showed the best success rates (78.9%), followed by omalizumab (50%) and benralizumab treatments (50%). However, a correlation between biomarkers and treatment success could not be found. Discussion/Conclusion: Treatment of CRSwNP with biologicals is a promising option for severe cases not responding to conventional therapy, including difficult-to-treat patients. Predictive biomarkers for a successful treatment could not be identified, but the reduction of eosinophilic cationic protein was linked with the response.
- Published
- 2021
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