26 results on '"Ahout, Inge M. L."'
Search Results
2. Palliative care for children: methodology for the development of a national clinical practice guideline.
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van Teunenbroek, Kim C., Kremer, Leontien C. M., Verhagen, A. A. Eduard, Verheijden, Johannes M. A., Rippen, Hester, Borggreve, Brigitt C. M., Michiels, Erna M. C., Mulder, Renée L., Ahout, Inge M. L., Alsem, Mattijs W., van den Bergh, Esther M. M., Berkhout, Loes, Bindels-de Heus, Karin G. C. B., Brinkhorst, Govert, Colenbrander, Arno, Corel, Linda, Delsman-van Gelder, Catharina M., van Dijk, Jennifer, Fahner, Jurrianne C., and Falkenburg, Jeannette L.
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SERVICES for caregivers ,STAKEHOLDER analysis ,PEDIATRICS ,EVIDENCE-based medicine ,MEDICAL personnel ,CATASTROPHIC illness ,MEDICAL protocols ,PATIENTS' families ,ADVANCE directives (Medical care) ,QUALITY assurance ,DECISION making ,PALLIATIVE treatment ,PARENTS ,BEREAVEMENT ,CHILDREN ,ADOLESCENCE - Abstract
Background: Provision of paediatric palliative care for children with life-threatening or life-limiting conditions and their families is often complex. Guidelines can support professionals to deliver high quality care. Stakeholders expressed the need to update the first Dutch paediatric palliative care guideline with new scientific literature and new topics. This paper provides an overview of the methodology that is used for the revision of the Dutch paediatric palliative care guideline and a brief presentation of the identified evidence. Methods: The revised paediatric palliative care guideline was developed with a multidisciplinary guideline panel of 72 experts in paediatric palliative care and nine (bereaved) parents of children with life-threatening or life-limiting conditions. The guideline covered multiple topics related to (refractory) symptom treatment, advance care planning and shared-decision making, organisation of care, psychosocial care, and loss and bereavement. We established six main working groups that formulated 38 clinical questions for which we identified evidence by updating two existing systematic literature searches. The GRADE (CERQual) methodology was used for appraisal of evidence. Furthermore, we searched for additional literature such as existing guidelines and textbooks to deal with lack of evidence. Results: The two systematic literature searches yielded a total of 29 RCTs or systematic reviews of RCTs on paediatric palliative care interventions and 22 qualitative studies on barriers and facilitators of advance care planning and shared decision-making. We identified evidence for 14 out of 38 clinical questions. Furthermore, we were able to select additional literature (29 guidelines, two textbooks, and 10 systematic reviews) to deal with lack of evidence. Conclusions: The revised Dutch paediatric palliative care guideline addresses many topics. However, there is limited evidence to base recommendations upon. Our methodology will combine the existing evidence in scientific literature, additional literature, expert knowledge, and perspectives of patients and their families to provide recommendations. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Natural killer cell activation by respiratory syncytial virus-specific antibodies is decreased in infants with severe respiratory infections and correlates with Fc-glycosylation
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van Erp, Elisabeth A., primary, Lakerveld, Anke J., additional, de Graaf, Erik, additional, Larsen, Mads D., additional, Schepp, Rutger M., additional, Hipgrave Ederveen, Agnes L., additional, Ahout, Inge M. L., additional, de Haan, Cornelis A. M., additional, Wuhrer, Manfred, additional, Luytjes, Willem, additional, Ferwerda, Gerben, additional, Vidarsson, Gestur, additional, and van Kasteren, Puck B., additional
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- 2019
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4. Nationwide Study on the Course of Influenza A (H1N1) Infections in Hospitalized Children in the Netherlands During the Pandemic 2009–2010
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Ahout, Inge M. L., primary, Philipsen, Ria L. A., additional, Las, Mariëtte, additional, Baysan, Meryem, additional, Brus, Frank, additional, Rahamat-Langendoen, Jeanette C., additional, Roeleveld, Nel, additional, Fraaij, Pieter L., additional, Osterhaus, Albert D. M. E., additional, Ferwerda, Gerben, additional, and de Groot, Ronald, additional
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- 2018
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5. In vitro enhancement of RSV infection by maternal antibodies does not explain disease severity in infants
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van Erp, Elisabeth A, van Kasteren, Puck B, Guichelaar, Teun, Ahout, Inge M L, de Haan, Cornelis A M, Luytjes, Willem, Ferwerda, Gerben, Wicht, Oliver, and dI&I I&I-1
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maternal antibodies ,respiratory syncytial virus ,pediatricinfectious disease ,antibodyfunction ,cotton rat ,neutralizing antibodies ,antibody-dependent enhancement ,neonatal immunology ,virology - Abstract
Respiratory syncytial virus (RSV) is the leading cause of severe respiratory illness in infants. At this young age, infants typically depend on maternally transferred antibodies (matAbs) and their innate immune system for protection against infections. RSV-specific matAbs are thought to protect from severe illness, yet severe RSV disease occurs mainly below 6 months of age, when neutralizing matAb levels are present. To investigate this discrepancy, we asked if disease severity is related to antibody properties other than neutralization. Some antibody effector functions are mediated via their Fc binding region. However, it has been shown that this binding may lead to antibody-dependent enhancement (ADE) of infection or reduction of neutralization, both possibly leading to more disease. In this study, we first showed that high levels of ADE of RSV infection occur in monocytic THP-1 cells in the presence of RSV antibodies and that neutralization by these antibodies was reduced in Vero cells when they were transduced with Fc gamma receptors. We then demonstrated that antibodies from cotton rats with formalin-inactivated- (FI-) RSV-induced pulmonary pathology were capable of causing ADE. Human matAbs also caused ADE and were less neutralizing in vitro in cells that carry Fc receptors. However, these effects were unrelated to disease severity because they were seen both in uninfected controls and in infants hospitalized with different levels of RSV disease severity. We conclude that ADE and reduction of neutralization are unlikely to be involved in RSV disease in infants with neutralizing matAbs.IMPORTANCE It is unclear why severity of RSV disease peaks at the age when infants have neutralizing levels of maternal antibodies. Additionally, the exact reason for FI-RSV-induced enhanced disease, as seen in the 1960's vaccine trials, is still unclear. We hypothesized that antibodies present in either of these conditions could contribute to disease severity. Antibodies can have effects that may lead to more disease instead of protection. We investigated two of those effects: antibody-dependent enhancement of infection (ADE) and neutralization reduction. We show that ADE occurs in vitro with antibodies from FI-RSV-immunized RSV-infected cotton rats. Moreover, passively acquired maternal antibodies from infants had the capacity to induce ADE and reduction of neutralization. However, no clear association with disease severity was seen, ruling out that these properties explain disease in the presence of maternal antibodies. Our data contribute to a better understanding of the impact of antibodies on RSV disease in infants.
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- 2017
6. Characteristics of RSV-Specific Maternal Antibodies in Plasma of Hospitalized, Acute RSV Patients under Three Months of Age
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Jans, Jop, Wicht, Oliver, Widjaja, Ivy, Ahout, Inge M L, de Groot, Ronald, Guichelaar, Teun, Luytjes, Willem, de Jonge, Marien I, de Haan, Cornelis A M, Ferwerda, Gerben, dI&I I&I-1, and dI&I I&I-1
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Male ,0301 basic medicine ,Pulmonology ,Physiology ,viruses ,Antibody Affinity ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,lcsh:Medicine ,Disease ,Antibodies, Viral ,Biochemistry ,Severity of Illness Index ,Serology ,Families ,Epitopes ,Antibody Specificity ,Immune Physiology ,Medicine and Health Sciences ,Enzyme-Linked Immunoassays ,lcsh:Science ,Children ,Antigens, Viral ,Immune System Proteins ,Multidisciplinary ,biology ,Antibody titer ,Hematology ,respiratory system ,Recombinant Proteins ,Body Fluids ,3. Good health ,Hospitalization ,Chemistry ,Infectious Diseases ,Blood ,Physical Sciences ,Acute Disease ,Female ,Anatomy ,medicine.symptom ,Antibody ,Infants ,Research Article ,Chemical Elements ,Infectious Disease Control ,Immunology ,Respiratory Syncytial Virus Infections ,Research and Analysis Methods ,Tachypnea ,Antibodies ,Blood Plasma ,Virus ,03 medical and health sciences ,Antigen ,Neutralization Tests ,medicine ,Humans ,Avidity ,Immunoassays ,Glycoproteins ,business.industry ,lcsh:R ,Biology and Life Sciences ,Proteins ,Infant ,Oxygen ,030104 developmental biology ,Age Groups ,Immunoglobulin G ,Respiratory Syncytial Virus, Human ,People and Places ,Respiratory Infections ,Immunologic Techniques ,biology.protein ,Population Groupings ,lcsh:Q ,business - Abstract
Contains fulltext : 170145.pdf (Publisher’s version ) (Open Access) Respiratory syncytial virus (RSV) is the leading cause for respiratory illness that requires hospitalization in infancy. High levels of maternal antibodies can protect against RSV infection. However, RSV-infected infants can suffer from severe disease symptoms even in the presence of high levels of RSV-specific antibodies. This study analyzes several serological characteristics to explore potential deficiencies or surpluses of antibodies that could relate to severe disease symptoms. We compare serum antibodies from hospitalized patients who suffered severe symptoms as well as uninfected infants. Disease severity markers were oxygen therapy, tachypnea, oxygen saturation, admission to the intensive care unit and duration of hospitalization. Antibodies against RSV G protein and a prefusion F epitope correlated with in vitro neutralization. Avidity of RSV-specific IgG antibodies was lower in RSV-infected infants compared to uninfected controls. Severe disease symptoms were unrelated to RSV-specific IgG antibody titers, avidity of RSV-IgG, virus neutralization capacity or titers against pre- and postfusion F or G protein ectodomains and the prefusion F antigenic site O. In conclusion, the detailed serological characterization did not indicate dysfunctional or epitope-skewed composition of serum antibodies in hospitalized RSV-infected infants suffering from severe disease symptoms. It remains unclear, whether specific antibody fractions could diminish disease symptoms.
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- 2017
7. Prospective observational study in two Dutch hospitals to assess the performance of inflammatory plasma markers to determine disease severity of viral respiratory tract infections in children
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Ahout, Inge M L, Brand, Kim H, Zomer, Aldert, van den Hurk, Wilhelma H, Schilders, Geurt, Brouwer, Marianne L, Neeleman, Chris, de Groot, Ronald, Ferwerda, Gerben, dI&I I&I-4, Pediatrics, and dI&I I&I-4
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0301 basic medicine ,Male ,Pediatrics ,medicine.medical_specialty ,severity of disease ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Disease ,Severity of Illness Index ,03 medical and health sciences ,respiratory infections ,0302 clinical medicine ,Predictive Value of Tests ,Severity of illness ,Medicine ,Humans ,Prospective Studies ,Respiratory system ,Prospective cohort study ,Respiratory Tract Infections ,Netherlands ,PTX3 ,Respiratory tract infections ,business.industry ,Research ,Infant ,030208 emergency & critical care medicine ,Paediatrics ,General Medicine ,Blood Proteins ,3. Good health ,Hospitalization ,properdin ,030104 developmental biology ,Respiratory failure ,Virus Diseases ,Predictive value of tests ,Acute Disease ,Biomarker (medicine) ,biomarker ,Female ,business ,CRP ,SAP ,Biomarkers - Abstract
Contains fulltext : 177243.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Respiratory viruses causing lower respiratory tract infections (LRTIs) are a major cause of hospital admissions in children. Since the course of these infections is unpredictable with potential fast deterioration into respiratory failure, infants are easily admitted to the hospital for observation. The aim of this study was to examine whether systemic inflammatory markers can be used to predict severity of disease in children with respiratory viral infections. METHODS: Blood and nasopharyngeal washings from children
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- 2017
8. Nasopharyngeal gene expression, a novel approach to study the course of respiratory syncytial virus infection
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van den Kieboom, Corné H, Ahout, Inge M L, Zomer, Aldert, Brand, Kim H, de Groot, Ronald, Ferwerda, Gerben, de Jonge, Marien I, LS Klinisch Onderzoek Wagenaar, and LS Klinisch Onderzoek Wagenaar
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Genetic Markers ,Male ,Pulmonary and Respiratory Medicine ,Tetraspanins ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Respiratory Syncytial Virus Infections ,Virus ,Viral Respiratory Tract Infection ,Predictive Value of Tests ,Nasopharyngeal aspirate ,Nasopharynx ,medicine ,Humans ,Chemokine CCL7 ,Ubiquitin D ,Respiratory tract infections ,business.industry ,Gene Expression Profiling ,Mucins ,Patient Acuity ,Infant ,Prostatic Secretory Proteins ,Recovery of Function ,Microarray Analysis ,Prognosis ,medicine.disease ,Virology ,Gene expression profiling ,Pneumonia ,Bronchiolitis ,Child, Preschool ,Host-Pathogen Interactions ,Immunology ,Female ,business - Abstract
Respiratory syncytial virus (RSV) causes mild infections in the vast majority of children. However, in some cases, it causes severe disease, such as bronchiolitis and pneumonia. Development of severe RSV infection is determined by the host response. Therefore, the main aim of this study was to identify biomarkers associated with severe RSV infection.To identify biomarkers, nasopharyngeal gene expression was profiled by microarray studies, resulting in the selection of five genes: ubiquitin D, tetraspanin 8, mucin 13, β-microseminoprotein and chemokine ligand 7.These genes were validated by real-time quantitative PCR in an independent validation cohort, which confirmed significant differences in gene expression between mildly and severely infected and between recovery and acute patients.Nasopharyngeal aspirate samples are regularly taken when a viral respiratory tract infection is suspected. In this article, we describe a method to discriminate between mild and severe RSV infection based on differential host gene expression. The combination of pathogen detection and host gene expression analysis in nasopharyngeal aspirates will significantly improve the diagnosis and prognosis of respiratory tract infections.
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- 2014
9. Characteristics of RSV-Specific Maternal Antibodies in Plasma of Hospitalized, Acute RSV Patients under Three Months of Age
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dI&I I&I-1, Jans, Jop, Wicht, Oliver, Widjaja, Ivy, Ahout, Inge M L, de Groot, Ronald, Guichelaar, Teun, Luytjes, Willem, de Jonge, Marien I, de Haan, Cornelis A M, Ferwerda, Gerben, dI&I I&I-1, Jans, Jop, Wicht, Oliver, Widjaja, Ivy, Ahout, Inge M L, de Groot, Ronald, Guichelaar, Teun, Luytjes, Willem, de Jonge, Marien I, de Haan, Cornelis A M, and Ferwerda, Gerben
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- 2017
10. In vitro enhancement of RSV infection by maternal antibodies does not explain disease severity in infants
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dI&I I&I-1, van Erp, Elisabeth A, van Kasteren, Puck B, Guichelaar, Teun, Ahout, Inge M L, de Haan, Cornelis A M, Luytjes, Willem, Ferwerda, Gerben, Wicht, Oliver, dI&I I&I-1, van Erp, Elisabeth A, van Kasteren, Puck B, Guichelaar, Teun, Ahout, Inge M L, de Haan, Cornelis A M, Luytjes, Willem, Ferwerda, Gerben, and Wicht, Oliver
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- 2017
11. Prospective observational study in two Dutch hospitals to assess the performance of inflammatory plasma markers to determine disease severity of viral respiratory tract infections in children
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dI&I I&I-4, Ahout, Inge M L, Brand, Kim H, Zomer, Aldert, van den Hurk, Wilhelma H, Schilders, Geurt, Brouwer, Marianne L, Neeleman, Chris, de Groot, Ronald, Ferwerda, Gerben, dI&I I&I-4, Ahout, Inge M L, Brand, Kim H, Zomer, Aldert, van den Hurk, Wilhelma H, Schilders, Geurt, Brouwer, Marianne L, Neeleman, Chris, de Groot, Ronald, and Ferwerda, Gerben
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- 2017
12. Transcriptome assists prognosis of disease severity in respiratory syncytial virus infected infants
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Jong, Victor L, Ahout, Inge M L, van den Ham, Henk-Jan, Jans, Jop, Zaaraoui-Boutahar, Fatiha, Zomer, Aldert, Simonetti, Elles, Bijl, Maarten A, Brand, H Kim, van IJcken, Wilfred F J, de Jonge, Marien I, Fraaij, Pieter L, de Groot, Ronald, Osterhaus, Albert D M E, Eijkemans, Marinus J, Ferwerda, Gerben, Andeweg, Arno C, LS Klinisch Onderzoek Wagenaar, dI&I I&I-4, Virology, Cell biology, Pediatrics, LS Klinisch Onderzoek Wagenaar, and dI&I I&I-4
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Male ,0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Support Vector Machine ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Respiratory Syncytial Virus Infections ,Disease ,Paediatric research ,Severity of Illness Index ,Article ,03 medical and health sciences ,Prognostic markers ,Lower respiratory tract infection ,Severity of illness ,Journal Article ,medicine ,Bronchiolitis, Viral ,Humans ,Multidisciplinary ,Receiver operating characteristic ,business.industry ,Gene Expression Profiling ,Infant, Newborn ,Infant ,Genomic signature ,Common cold ,Gene signature ,Prognosis ,medicine.disease ,Respiratory Syncytial Viruses ,030104 developmental biology ,Bronchiolitis ,Female ,Transcriptome ,business - Abstract
Contains fulltext : 171838.pdf (Publisher’s version ) (Open Access) Respiratory syncytial virus (RSV) causes infections that range from common cold to severe lower respiratory tract infection requiring high-level medical care. Prediction of the course of disease in individual patients remains challenging at the first visit to the pediatric wards and RSV infections may rapidly progress to severe disease. In this study we investigate whether there exists a genomic signature that can accurately predict the course of RSV. We used early blood microarray transcriptome profiles from 39 hospitalized infants that were followed until recovery and of which the level of disease severity was determined retrospectively. Applying support vector machine learning on age by sex standardized transcriptomic data, an 84 gene signature was identified that discriminated hospitalized infants with eventually less severe RSV infection from infants that suffered from most severe RSV disease. This signature yielded an area under the receiver operating characteristic curve (AUC) of 0.966 using leave-one-out cross-validation on the experimental data and an AUC of 0.858 on an independent validation cohort consisting of 53 infants. A combination of the gene signature with age and sex yielded an AUC of 0.971. Thus, the presented signature may serve as the basis to develop a prognostic test to support clinical management of RSV patients.
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- 2016
13. In Vitro Enhancement of Respiratory Syncytial Virus Infection by Maternal Antibodies Does Not Explain Disease Severity in Infants
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van Erp, Elisabeth A., primary, van Kasteren, Puck B., additional, Guichelaar, Teun, additional, Ahout, Inge M. L., additional, de Haan, Cornelis A. M., additional, Luytjes, Willem, additional, Ferwerda, Gerben, additional, and Wicht, Oliver, additional
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- 2017
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14. Transcriptome assists prognosis of disease severity in respiratory syncytial virus infected infants
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LS Klinisch Onderzoek Wagenaar, dI&I I&I-4, Jong, Victor L, Ahout, Inge M L, van den Ham, Henk-Jan, Jans, Jop, Zaaraoui-Boutahar, Fatiha, Zomer, Aldert, Simonetti, Elles, Bijl, Maarten A, Brand, H Kim, van IJcken, Wilfred F J, de Jonge, Marien I, Fraaij, Pieter L, de Groot, Ronald, Osterhaus, Albert D M E, Eijkemans, Marinus J, Ferwerda, Gerben, Andeweg, Arno C, LS Klinisch Onderzoek Wagenaar, dI&I I&I-4, Jong, Victor L, Ahout, Inge M L, van den Ham, Henk-Jan, Jans, Jop, Zaaraoui-Boutahar, Fatiha, Zomer, Aldert, Simonetti, Elles, Bijl, Maarten A, Brand, H Kim, van IJcken, Wilfred F J, de Jonge, Marien I, Fraaij, Pieter L, de Groot, Ronald, Osterhaus, Albert D M E, Eijkemans, Marinus J, Ferwerda, Gerben, and Andeweg, Arno C
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- 2016
15. Transcriptome assists prognosis of disease severity in respiratory syncytial virus infected infants
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Biostatistiek Onderzoek, Longziekten patientenzorg, NVIC, Circulatory Health, JC onderzoeksprogramma Infectieziekten, JC onderzoeksprogramma Methodologie, Child Health, Jong, Victor L, Ahout, Inge M L, van den Ham, Henk-Jan, Jans, Jop, Zaaraoui-Boutahar, Fatiha, Zomer, Aldert, Simonetti, Elles, Bijl, Maarten A, Brand, H Kim, van IJcken, Wilfred F J, de Jonge, Marien I, Fraaij, Pieter L, de Groot, Ronald, Osterhaus, Albert D M E, Eijkemans, Marinus J, Ferwerda, Gerben, Andeweg, Arno C, Biostatistiek Onderzoek, Longziekten patientenzorg, NVIC, Circulatory Health, JC onderzoeksprogramma Infectieziekten, JC onderzoeksprogramma Methodologie, Child Health, Jong, Victor L, Ahout, Inge M L, van den Ham, Henk-Jan, Jans, Jop, Zaaraoui-Boutahar, Fatiha, Zomer, Aldert, Simonetti, Elles, Bijl, Maarten A, Brand, H Kim, van IJcken, Wilfred F J, de Jonge, Marien I, Fraaij, Pieter L, de Groot, Ronald, Osterhaus, Albert D M E, Eijkemans, Marinus J, Ferwerda, Gerben, and Andeweg, Arno C
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- 2016
16. Mucosal IgG Levels Correlate Better with Respiratory Syncytial Virus Load and Inflammation than Plasma IgG Levels
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Vissers, Marloes, primary, Ahout, Inge M. L., additional, de Jonge, Marien I., additional, and Ferwerda, Gerben, additional
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- 2016
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17. Reduced Expression of HLA-DR on Monocytes During Severe Respiratory Syncytial Virus Infections
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Ahout, Inge M. L., primary, Jans, Jop, additional, Haroutiounian, Lilid, additional, Simonetti, Elles R., additional, van der Gaast-de Jongh, Christa, additional, Diavatopoulos, Dimitri A., additional, de Jonge, Marien I., additional, de Groot, Ronald, additional, and Ferwerda, Gerben, additional
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- 2016
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18. Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells.
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Jans, Jop, Unger, Wendy W. J., Vissers, Marloes, Ahout, Inge M. L., Schreurs, Inge, Wickenhagen, Arthur, de Groot, Ronald, de Jonge, Marien I., and Ferwerda, Gerben
- Abstract
Abstract: Interferon gamma (IFN‐γ) plays an important role in the antiviral immune response during respiratory syncytial virus (RSV) infections. Monocytes and T cells are recruited to the site of RSV infection, but it is unclear whether cell‐cell interactions between monocytes and T cells regulate IFN‐γ production. In this study, micro‐array data identified the upregulation of sialic acid‐binding immunoglobulin‐type lectin 1 (Siglec‐1) in human RSV‐infected infants. In vitro, RSV increased expression of Siglec‐1 on healthy newborn and adult monocytes. RSV‐induced Siglec‐1 on monocytes inhibited IFN‐γ production by adult CD4
+ T cells. In contrast, IFN‐γ production by RSV in newborns was not affected by Siglec‐1. The ligand for Siglec‐1, CD43, is highly expressed on adult CD4+ T cells compared to newborns. Our data show that Siglec‐1 reduces IFN‐γ release by adult T cells possibly by binding to the highly expressed CD43. The Siglec‐1‐dependent inhibition of IFN‐γ in adults and the low expression of CD43 on newborn T cells provides a better understanding of the immune response against RSV in early life and adulthood. [ABSTRACT FROM AUTHOR]- Published
- 2018
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19. Nasopharyngeal gene expression, a novel approach to study the course of respiratory syncytial virus infection
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LS Klinisch Onderzoek Wagenaar, van den Kieboom, Corné H, Ahout, Inge M L, Zomer, Aldert, Brand, Kim H, de Groot, Ronald, Ferwerda, Gerben, de Jonge, Marien I, LS Klinisch Onderzoek Wagenaar, van den Kieboom, Corné H, Ahout, Inge M L, Zomer, Aldert, Brand, Kim H, de Groot, Ronald, Ferwerda, Gerben, and de Jonge, Marien I
- Published
- 2014
20. An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
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Vissers, Marloes, primary, Habets, Marrit N., primary, Ahout, Inge M. L., primary, Jans, Jop, primary, de Jonge, Marien I., primary, Diavatopoulos, Dimitri A., primary, and Ferwerda, Gerben, primary
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- 2013
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21. Mucosal IgG Levels Correlate Better with Respiratory Syncytial Virus Load and Inflammation than Plasma IgG Levels
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Vissers, Marloes, Ahout, Inge M. L., de Jonge, Marien I., and Ferwerda, Gerben
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ABSTRACTMaternal vaccination is currently considered a strategy against respiratory syncytial virus (RSV) infections. In RSV-infected infants, high mucosal IgG levels correlated better with reduced RSV load and lower mucosal CXCL10 levels than plasma IgG levels. For future vaccination strategies against RSV, more focus should be on the mucosal humoral immune response.
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- 2015
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22. Biosynthetic homeostasis and resilience of the complement system in health and infectious disease.
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Willems E, Alkema W, Keizer-Garritsen J, Suppers A, van der Flier M, Philipsen RHLA, van den Heuvel LP, Volokhina E, van der Molen RG, Herberg JA, Levin M, Wright VJ, Ahout IML, Ferwerda G, Emonts M, Boeddha NP, Rivero-Calle I, Torres FM, Wessels HJCT, de Groot R, van Gool AJ, Gloerich J, and de Jonge MI
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- Adolescent, Adult, C-Reactive Protein genetics, C-Reactive Protein immunology, Child, Child, Preschool, Clusterin genetics, Clusterin immunology, Communicable Diseases genetics, Complement Activation genetics, Complement System Proteins classification, Complement System Proteins isolation & purification, Female, Homeostasis, Humans, Infant, Infant, Newborn, Inflammation genetics, Male, Mass Spectrometry, Middle Aged, Young Adult, Communicable Diseases immunology, Complement Activation immunology, Complement System Proteins chemistry, Inflammation immunology
- Abstract
Background: The complement system is a central component of the innate immune system. Constitutive biosynthesis of complement proteins is essential for homeostasis. Dysregulation as a consequence of genetic or environmental cues can lead to inflammatory syndromes or increased susceptibility to infection. However, very little is known about steady state levels in children or its kinetics during infection., Methods: With a newly developed multiplex mass spectrometry-based method we analyzed the levels of 32 complement proteins in healthy individuals and in a group of pediatric patients infected with bacterial or viral pathogens., Findings: In plasma from young infants we found reduced levels of C4BP, ficolin-3, factor B, classical pathway components C1QA, C1QB, C1QC, C1R, and terminal pathway components C5, C8, C9, as compared to healthy adults; whereas the majority of complement regulating (inhibitory) proteins reach adult levels at very young age. Both viral and bacterial infections in children generally lead to a slight overall increase in complement levels, with some exceptions. The kinetics of complement levels during invasive bacterial infections only showed minor changes, except for a significant increase and decrease of CRP and clusterin, respectively., Interpretation: The combination of lower levels of activating and higher levels of regulating complement proteins, would potentially raise the threshold of activation, which might lead to suppressed complement activation in the first phase of life. There is hardly any measurable complement consumption during bacterial or viral infection. Altogether, expression of the complement proteins appears surprisingly stable, which suggests that the system is continuously replenished. FUND: European Union's Horizon 2020, project PERFORM, grant agreement No. 668303., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2019
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23. Prospective observational study in two Dutch hospitals to assess the performance of inflammatory plasma markers to determine disease severity of viral respiratory tract infections in children.
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Ahout IML, Brand KH, Zomer A, van den Hurk WH, Schilders G, Brouwer ML, Neeleman C, Groot R, and Ferwerda G
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- Acute Disease, Biomarkers blood, Blood Proteins analysis, Female, Humans, Infant, Male, Netherlands, Predictive Value of Tests, Prospective Studies, Respiratory Tract Infections diagnosis, Virus Diseases diagnosis, Hospitalization statistics & numerical data, Respiratory Tract Infections blood, Severity of Illness Index, Virus Diseases blood
- Abstract
Introduction: Respiratory viruses causing lower respiratory tract infections (LRTIs) are a major cause of hospital admissions in children. Since the course of these infections is unpredictable with potential fast deterioration into respiratory failure, infants are easily admitted to the hospital for observation. The aim of this study was to examine whether systemic inflammatory markers can be used to predict severity of disease in children with respiratory viral infections., Methods: Blood and nasopharyngeal washings from children <3 years of age with viral LRTI attending a hospital were collected within 24 hours (acute) and after 4-6 weeks (recovery). Patients were assigned to a mild (observation only), moderate (supplemental oxygen and/or nasogastric feeding) or severe (mechanical ventilation) group. Linear regression analysis was used to design a prediction rule using plasma levels of C reactive protein (CRP), serum amyloid A (SAA), pentraxin 3 (PTX3), serum amyloid P component and properdin. This rule was tested in a validation cohort., Results: One hundred and four children (52% male) were included. A combination of CRP, SAA, PTX3 and properdin was a better indicator of severe disease compared with any of the individual makers and age (69% sensitivity (95% CI 50 to 83), 90% specificity (95% CI 80 to 96)). Validation in 141 patients resulted in 71% sensitivity (95% CI 53 to 85), 87% specificity (95% CI 79 to 92), negative predictive value of 64% (95% CI 47 to 78) and positive predictive value of 90% (95% CI 82 to 95). The prediction rule was not able to identify patients with a mild course of disease., Conclusion: A combination of CRP, SAA, PTX3 and properdin was able to identify children with a severe course of viral LRTI disease, even in children under 2 months of age. To assess the true impact on clinical management, these results should be validated in a prospective randomised control study., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
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- 2017
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24. Characteristics of RSV-Specific Maternal Antibodies in Plasma of Hospitalized, Acute RSV Patients under Three Months of Age.
- Author
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Jans J, Wicht O, Widjaja I, Ahout IM, de Groot R, Guichelaar T, Luytjes W, de Jonge MI, de Haan CA, and Ferwerda G
- Subjects
- Acute Disease, Antibody Affinity immunology, Antigens, Viral immunology, Epitopes immunology, Female, Glycoproteins immunology, Humans, Immunoglobulin G blood, Infant, Male, Neutralization Tests, Severity of Illness Index, Antibodies, Viral blood, Antibodies, Viral immunology, Antibody Specificity immunology, Hospitalization, Respiratory Syncytial Virus Infections blood, Respiratory Syncytial Virus Infections immunology, Respiratory Syncytial Virus, Human immunology
- Abstract
Respiratory syncytial virus (RSV) is the leading cause for respiratory illness that requires hospitalization in infancy. High levels of maternal antibodies can protect against RSV infection. However, RSV-infected infants can suffer from severe disease symptoms even in the presence of high levels of RSV-specific antibodies. This study analyzes several serological characteristics to explore potential deficiencies or surpluses of antibodies that could relate to severe disease symptoms. We compare serum antibodies from hospitalized patients who suffered severe symptoms as well as uninfected infants. Disease severity markers were oxygen therapy, tachypnea, oxygen saturation, admission to the intensive care unit and duration of hospitalization. Antibodies against RSV G protein and a prefusion F epitope correlated with in vitro neutralization. Avidity of RSV-specific IgG antibodies was lower in RSV-infected infants compared to uninfected controls. Severe disease symptoms were unrelated to RSV-specific IgG antibody titers, avidity of RSV-IgG, virus neutralization capacity or titers against pre- and postfusion F or G protein ectodomains and the prefusion F antigenic site Ø. In conclusion, the detailed serological characterization did not indicate dysfunctional or epitope-skewed composition of serum antibodies in hospitalized RSV-infected infants suffering from severe disease symptoms. It remains unclear, whether specific antibody fractions could diminish disease symptoms., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2017
- Full Text
- View/download PDF
25. Nasopharyngeal gene expression, a novel approach to study the course of respiratory syncytial virus infection.
- Author
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van den Kieboom CH, Ahout IM, Zomer A, Brand KH, de Groot R, Ferwerda G, and de Jonge MI
- Subjects
- Child, Preschool, Female, Gene Expression Profiling, Genetic Markers, Humans, Infant, Male, Microarray Analysis, Nasopharynx virology, Patient Acuity, Predictive Value of Tests, Prognosis, Recovery of Function genetics, Chemokine CCL7 genetics, Host-Pathogen Interactions genetics, Mucins genetics, Prostatic Secretory Proteins genetics, Respiratory Syncytial Virus Infections diagnosis, Respiratory Syncytial Virus Infections genetics, Respiratory Syncytial Virus Infections physiopathology, Respiratory Syncytial Virus Infections virology, Tetraspanins genetics
- Abstract
Respiratory syncytial virus (RSV) causes mild infections in the vast majority of children. However, in some cases, it causes severe disease, such as bronchiolitis and pneumonia. Development of severe RSV infection is determined by the host response. Therefore, the main aim of this study was to identify biomarkers associated with severe RSV infection. To identify biomarkers, nasopharyngeal gene expression was profiled by microarray studies, resulting in the selection of five genes: ubiquitin D, tetraspanin 8, mucin 13, β-microseminoprotein and chemokine ligand 7. These genes were validated by real-time quantitative PCR in an independent validation cohort, which confirmed significant differences in gene expression between mildly and severely infected and between recovery and acute patients. Nasopharyngeal aspirate samples are regularly taken when a viral respiratory tract infection is suspected. In this article, we describe a method to discriminate between mild and severe RSV infection based on differential host gene expression. The combination of pathogen detection and host gene expression analysis in nasopharyngeal aspirates will significantly improve the diagnosis and prognosis of respiratory tract infections., (Copyright ©ERS 2015.)
- Published
- 2015
- Full Text
- View/download PDF
26. Use of MMP-8 and MMP-9 to assess disease severity in children with viral lower respiratory tract infections.
- Author
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Brand KH, Ahout IM, de Groot R, Warris A, Ferwerda G, and Hermans PW
- Subjects
- Female, Gene Expression, Granulocytes enzymology, HeLa Cells, Humans, Infant, Leukocytes, Mononuclear enzymology, Male, Matrix Metalloproteinase 8 blood, Matrix Metalloproteinase 8 genetics, Matrix Metalloproteinase 9 blood, Matrix Metalloproteinase 9 genetics, Nasal Mucosa enzymology, Nasal Mucosa virology, Neutrophils enzymology, Neutrophils virology, Pharynx enzymology, Pharynx virology, Prospective Studies, Respiratory Syncytial Virus Infections pathology, Respiratory Syncytial Virus Infections virology, Respiratory Tract Infections pathology, Respiratory Tract Infections virology, Severity of Illness Index, Statistics, Nonparametric, Matrix Metalloproteinase 8 metabolism, Matrix Metalloproteinase 9 metabolism, Respiratory Syncytial Virus Infections enzymology, Respiratory Syncytial Viruses, Respiratory Tract Infections enzymology
- Abstract
Matrix metalloproteinases (MMPs) play an important role in respiratory inflammatory diseases, such as asthma and chronic obstructive pulmonary disease. It was hypothesized that MMP-8 and MMP-9 may function as biological markers to assess disease severity in viral lower respiratory tract infections in children. MMP-8 and MMP-9 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) and granulocytes obtained in both the acute and recovery phase from 153 children with mild, moderate, and severe viral lower respiratory tract infections were determined using real-time PCR. In addition, MMP-8 and MMP-9 concentrations in blood and nasopharyngeal specimens were determined during acute mild, moderate, and severe infection, and after recovery using ELISA. Furthermore, PBMCs and neutrophils obtained from healthy volunteers were stimulated with RSV, LPS (TLR4 agonist), and Pam3Cys (TLR2 agonist) in vitro. Disease severity of viral lower respiratory tract infections in children is associated with increased expression levels of the MMP-8 and MMP-9 genes in both PBMCs and granulocytes. On the contrary, in vitro experiments showed that MMP-8 and MMP-9 mRNA and protein expression in PBMCs and granulocytes is not induced by stimulation with RSV, the most frequent detected virus in young children with viral lower respiratory tract infections. These data indicate that expression levels of the MMP-8 and MMP-9 genes in both PBMCs and neutrophils are associated with viral lower respiratory tract infections disease severity. These observations justify future validation in independent prospective study cohorts of the usefulness of MMP-8 and MMP-9 as potential markers for disease severity in viral respiratory infections., (Copyright © 2012 Wiley Periodicals, Inc.)
- Published
- 2012
- Full Text
- View/download PDF
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