9 results on '"Thwaites, Ryan S"'
Search Results
2. Single‐cell immune profiling reveals markers of emergency myelopoiesis that distinguish severe from mild respiratory syncytial virus disease in infants.
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Zivanovic, Nevena, Öner, Deniz, Abraham, Yann, McGinley, Joseph, Drysdale, Simon B., Wildenbeest, Joanne G., Crabbe, Marjolein, Vanhoof, Greet, Thys, Kim, Thwaites, Ryan S., Robinson, Hannah, Bont, Louis, Openshaw, Peter J. M., Martinón‐Torres, Federico, Pollard, Andrew J., and Aerssens, Jeroen
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RESPIRATORY syncytial virus infections ,INFANT diseases ,RESPIRATORY syncytial virus ,B cells - Abstract
Whereas most infants infected with respiratory syncytial virus (RSV) show no or only mild symptoms, an estimated 3 million children under five are hospitalized annually due to RSV disease. This study aimed to investigate biological mechanisms and associated biomarkers underlying RSV disease heterogeneity in young infants, enabling the potential to objectively categorize RSV‐infected infants according to their medical needs. Immunophenotypic and functional profiling demonstrated the emergence of immature and progenitor‐like neutrophils, proliferative monocytes (HLA‐DRLow, Ki67+), impaired antigen‐presenting function, downregulation of T cell response and low abundance of HLA‐DRLow B cells in severe RSV disease. HLA‐DRLow monocytes were found as a hallmark of RSV‐infected infants requiring hospitalization. Complementary transcriptomics identified genes associated with disease severity and pointed to the emergency myelopoiesis response. These results shed new light on mechanisms underlying the pathogenesis and development of severe RSV disease and identified potential new candidate biomarkers for patient stratification. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Neutrophil activation in RSV: close encounters of the chemokined.
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Thwaites, Ryan S
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RESPIRATORY syncytial virus infections ,NEUTROPHILS ,RESPIRATORY syncytial virus - Abstract
Trans-epithelial migration and physical interaction are required for full activation of neutrophils during in vitro RSV infection. [ABSTRACT FROM AUTHOR]
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- 2023
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4. Immunological and Inflammatory Biomarkers of Susceptibility and Severity in Adult Respiratory Syncytial Virus Infections
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Wiseman, Dexter J, Thwaites, Ryan S, Drysdale, Simon B, Janet, Sophie, Donaldson, Gavin C, Wedzicha, Jadwiga A, Openshaw, Peter J, Nair, Harish, Campbell, Harry, Shi, Ting, Zhang, Shanshan, Li, You, Openshaw, Peter, Wedzicha, Jadwiga, Falsey, Ann, Miller, Mark, Beutels, Philippe, Bont, Louis, Pollard, Andrew, Molero, Eva, Martinon-Torres, Federico, Heikkinen, Terho, Meijer, Adam, Kølsen Fischer, Thea, van den Berge, Maarten, Giaquinto, Carlo, Mikolajczyk, Rafael, Hackett, Judy, Tafesse, Eskinder, Cai, Bing, Knirsch, Charles, Gonzalez Lopez, Antonio, Dieussaert, Ilse, Dermateau, Nadia, Stoszek, Sonia, Gallichan, Scott, Kieffer, Alexia, Demont, Clarisse, Cheret, Arnaud, Gavart, Sandra, Aerssens, Jeroen, Wyffels, Veronique, Cleenewerck, Matthias, Fuentes, Robert, Rosen, Brian, Imperial College Healthcare NHS Trust- BRC Funding, National Institute for Health Research, Medical Research Council (MRC), Commission of the European Communities, Wellcome Trust, and GlaxoSmithKline Biologicals
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respiratory syncytial virus ,SERUM ANTIBODY ,Respiratory System ,MPO ,severity ,Disease ,CD8-Positive T-Lymphocytes ,RESCEU ,Severity of Illness Index ,0302 clinical medicine ,Immunology and Allergy ,FAILURE ,030212 general & internal medicine ,PROTECTION ,Neutralizing antibody ,11 Medical and Health Sciences ,Immunity, Cellular ,0303 health sciences ,COPD ,medicine.diagnostic_test ,biology ,adult ,RSV ,neutralizing antibody ,respiratory system ,3. Good health ,Infectious Diseases ,INFLUENZA ,Bronchiolitis ,Biomarker (medicine) ,biomarker ,Viral load ,Life Sciences & Biomedicine ,Immunology ,Respiratory Syncytial Virus Infections ,Microbiology ,03 medical and health sciences ,Critical Care Medicine ,General & Internal Medicine ,Severity of illness ,medicine ,Humans ,HUMORAL IMMUNITY ,030304 developmental biology ,Inflammation ,IL-6 ,Science & Technology ,Interleukin-6 ,business.industry ,Interleukin-8 ,MEMORY ,06 Biological Sciences ,medicine.disease ,Antibodies, Neutralizing ,Bronchoalveolar lavage ,VIRAL LOAD ,Respiratory Syncytial Virus, Human ,biology.protein ,T-CELLS ,RISK-FACTORS ,RESCEU Investigators ,business ,Biomarkers ,RESPONSES - Abstract
BackgroundRespiratory syncytial virus (RSV) is the most common cause of bronchiolitis in young infants. However, it is also a significant pathogen in older adults. Validated biomarkers of RSV disease severity would benefit diagnostics, treatment decisions, and prophylactic interventions. This review summarizes knowledge of biomarkers for RSV disease in adults.MethodsA literature review was performed using Ovid Medline, Embase, Global health, Scopus, and Web of Science for articles published 1946–October 2016. Nine articles were identified plus 9 from other sources.ResultsFrom observational studies of natural infection and challenge studies in volunteers, biomarkers of RSV susceptibility or disease severity in adults were: (1) lower anti-RSV neutralizing antibodies, where neutralizing antibody (and local IgA) may be a correlate of susceptibility/severity; (2) RSV-specific CD8+ T cells in bronchoalveolar lavage fluid preinfection (subjects with higher levels had less severe illness); and (3) elevated interleukin-6 (IL-6), IL-8, and myeloperoxidase levels in the airway are indicative of severe infection.ConclusionsFactors determining susceptibility to and severity of RSV disease in adults have not been well defined. Respiratory mucosal antibodies and CD8+ T cells appear to contribute to preventing infection and modulation of disease severity. Studies of RSV pathogenesis in at-risk populations are needed.
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- 2020
5. Reduced Nasal Viral Load and IFN Responses in Infants with Respiratory Syncytial Virus Bronchiolitis and Respiratory Failure.
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Thwaites, Ryan S, Coates, Matthew, Ito, Kazuhiro, Ghazaly, Marwa, Feather, Calandra, Abdulla, Farhana, Tunstall, Tanushree, Jain, Pooja, Cass, Lindsey, Rapeport, Garth, Hansel, Trevor T, Nadel, Simon, and Openshaw, Peter
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Rationale: Respiratory syncytial virus (RSV) bronchiolitis is a major cause of morbidity and mortality in infancy. Severe disease is believed to result from uncontrolled viral replication, an excessive immune response, or both.Objectives: To determine RSV load and immune mediator levels in nasal mucosal lining fluid by serial sampling of nasal fluids from cases of moderate and severe bronchiolitis over the course of infection.Methods: Infants with viral bronchiolitis necessitating admission (n = 55) were recruited from a pediatric center during 2016 and 2017. Of these, 30 were RSV infected (18 "moderate" and 12 mechanically ventilated "severe"). Nasal fluids were sampled frequently over time using nasosorption devices and nasopharyngeal aspiration. Hierarchical clustering of time-weighted averages was performed to investigate cytokine and chemokine levels, and gene expression profiling was conducted.Measurements and Main Results: Unexpectedly, cases with severe RSV bronchiolitis had lower nasal viral loads and reduced IFN-γ and C-C chemokine ligand 5/RANTES (regulated upon activation, normal T cell expressed and secreted) levels than those with moderate disease, especially when allowance was made for disease duration (all P < 0.05). Reduced cytokine/chemokine levels in severe disease were also seen in children with other viral infections. Gene expression analysis of nasopharyngeal aspiration samples (n = 43) confirmed reduced type-I IFN gene expression in severe bronchiolitis accompanied by enhanced expression of MUC5AC and IL17A.Conclusions: Infants with severe RSV bronchiolitis have lower nasal viral load, CXCL10 (C-X-C motif chemokine ligand 10)/IP-10, and type-I IFN levels than moderately ill children, but enhanced MUC5AC (mucin-5AC) and IL17A gene expression in nasal cells. [ABSTRACT FROM AUTHOR]- Published
- 2018
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6. The Respiratory Mucosa: Front and Center in Respiratory Syncytial Virus Disease.
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Thwaites, Ryan S. and Openshaw, Peter J.
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BRONCHIOLITIS ,LUNG infections ,RESPIRATORY syncytial virus ,RESPIRATORY syncytial virus infections ,ANIMAL models in research ,IMMUNITY ,LYMPHOCYTES ,TYPE 2 diabetes ,RESPIRATORY mucosa ,BRONCHIOLE diseases - Abstract
The article offers information on the Infantile bronchiolitis is a major scourge of early childhood, and winter outbreaks that fill the pediatric wards with wearisome regularity. It mentions that most infants will be infected by respiratory syncytial virus (RSV) before their second birthday; and also mentions that animal models have advanced our understanding of the pathogenesis of bronchiolitis.
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- 2019
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7. Nasosorption as a Minimally Invasive Sampling Procedure: Mucosal Viral Load and Inflammation in Primary RSV Bronchiolitis.
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Thwaites, Ryan S., Ito, Kazuhiro, Chingono, Jasmine M. S., Coates, Matthew, Jarvis, Hannah C., Tunstall, Tanushree, Anderson-Dring, Lauren, Cass, Lindsey, Rapeport, Garth, Openshaw, Peter J., Nadel, Simon, and Hansel, Trevor T.
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LAPAROSCOPIC surgery , *BRONCHIOLITIS , *INFANT diseases , *INTERFERONS , *INTERLEUKIN-10 , *ARTIFICIAL respiration , *BRONCHIOLE diseases , *CYTOKINES , *INFLAMMATION , *INTERLEUKINS , *NASAL mucosa , *RESPIRATORY syncytial virus , *VIRAL load , *CASE-control method , *RESPIRATORY syncytial virus infections , *DIAGNOSIS - Abstract
Background: Existing respiratory mucosal sampling methods are flawed, particularly in a pediatric bronchiolitis setting.Methods: Twenty-four infants with bronchiolitis were recruited: 12 were respiratory syncytial virus (RSV)-positive, 12 were RSV-negative. Infants were sampled by nasosorption and nasopharyngeal aspiration (NPA).Results: Nasosorption was well tolerated and identified all RSV+ samples. RSV load measured by nasosorption (but not NPA) correlated with length of hospital stay (P = .04) and requirement for mechanical ventilation (P = .03). Nasosorption (but not NPA) levels of interferon γ, interleukin 1β, CCL5/RANTES, and interleukin 10 (IL-10) were elevated in RSV+ bronchiolitis (all P < .05), furthermore CCL5 and IL-10 correlated with RSV load (P < .05).Conclusions: Nasosorption allowed measurement of RSV load and the mucosal inflammatory response in infants. [ABSTRACT FROM AUTHOR]- Published
- 2017
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8. A New Role for CXCL4 in Respiratory Syncytial Virus Disease.
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Wiseman, Dexter J., Thwaites, Ryan S., and Openshaw, Peter J. M.
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CHEMOKINES ,LIGANDS (Biochemistry) ,RESPIRATORY syncytial virus ,ENTEROVIRUSES ,HEPARAN sulfate ,RESPIRATORY syncytial virus infections - Abstract
The article describes a hitherto unknown inhibitory effect of chemokine ligand 4 (CXCL4) on respiratory syncytial virus (RSV) infection, replication, and disease. Topics include CXCL4 inhibited replication of Enterovirus 71 (EV71) and Herpes simplex virus 1 (HSV1); and CXCL4 protects against RSV infection through inhibition of RSV attachment to heparan sulfate (HS) on the surface of target cells.
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- 2020
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9. Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection.
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Habibi, Maximillian S., Thwaites, Ryan S., Chang, Meiping, Jozwik, Agnieszka, Paras, Allan, Kirsebom, Freja, Varese, Augusto, Owen, Amber, Cuthbertson, Leah, James, Phillip, Tunstall, Tanushree, Nickle, David, Hansel, Trevor T., Moffatt, Miriam F., Johansson, Cecilia, Chiu, Christopher, and Openshaw, Peter J. M.
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INFLAMMATION , *RESPIRATORY syncytial virus , *IMMUNOGLOBULINS , *PATHOGENIC microorganisms , *VIRUSES - Abstract
The article presents a research on Neutrophilic inflammation in the respiratory mucosa predisposes to respiratory syncytial virus (RSV) infection. Topics include Variable transmissions govern by the immune status of the host, such as the presence of specific protective antibodies or T cells; and antibodies and T cells have limited efficacy against pathogens with pandemic potential but the intrinsic and innate mechanisms underlying protection when people being exposed to these viruses.
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- 2020
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