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2. Transcriptome assists prognosis of disease severity in respiratory syncytial virus infected infants

Author

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

Subjects
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.

Published
2016

3. Transcriptome assists prognosis of disease severity in respiratory syncytial virus infected infants

Author

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

Published
2016

4. Transcriptome assists prognosis of disease severity in respiratory syncytial virus infected infants

Author

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

Published
2016

5. Host Proteome Correlates of Vaccine-Mediated Enhanced Disease in a Mouse Model of Respiratory Syncytial Virus Infection

Author

van Diepen, Angela, primary, Brand, H. Kim, additional, de Waal, Leon, additional, Bijl, Maarten, additional, Jong, Victor L., additional, Kuiken, Thijs, additional, van Amerongen, Geert, additional, van den Ham, Henk-Jan, additional, Eijkemans, Marinus J., additional, Osterhaus, Albert D. M. E., additional, Hermans, Peter W. M., additional, and Andeweg, Arno C., additional

Published
2015
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6. Response to 12-0176

Author

Brand, H. Kim, primary, Borm, George, additional, Hermans, Peter, additional, and Warris, Adilia, additional

Published
2012
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8. Host Proteome Correlates of Vaccine-Mediated Enhanced Disease in a Mouse Model of Respiratory Syncytial Virus Infection.

Author

Diepen, Angela van, Brand, H. Kim, Waal, Leon de, Bijl, Maarten, Jong, Victor L., Kuiken, Thijs, van Amerongen, Geert, van den Ham, Henk-Jan, Eijkemans, Marinus J., Osterhaus, Albert D. M. E., Hermans, Peter W. M., and Andeweg, Arno C.

Subjects
*RESPIRATORY syncytial virus, *RESPIRATORY infections in children, *VACCINES, *IMMUNOPATHOLOGY, *IMMUNE response
Abstract

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants. Despite over 50 years of research, to date no safe and efficacious RSV vaccine has been licensed. Many experimental vaccination strategies failed to induce balanced T-helper (Th) responses and were associated with adverse effects such as hypersensitivity and immunopathology upon challenge. In this study, we explored the well-established recombinant vaccinia virus (rVV) RSV-F/RSV-G vaccination-challenge mouse model to study phenotypically distinct vaccine-mediated host immune responses at the proteome level. In this model, rVV-G priming and not rVV-F priming results in the induction of Th2 skewed host responses upon RSV challenge. Mass spectrometry- based spectral count comparisons enabled us to identify seven host proteins for which expression in lung tissue is associated with an aberrant Th2 skewed response characterized by the influx of eosinophils and neutrophils. These proteins are involved in processes related to the direct influx of eosinophils (eosinophil peroxidase [Epx]) and to chemotaxis and extravasation processes (Chil3 [chitinase-like-protein 3]) as well as to eosinophil and neutrophil homing signals to the lung (Itgam). In addition, the increased levels of Arg1 and Chil3 proteins point to a functional and regulatory role for alternatively activated macrophages and type 2 innate lymphoid cells in Th2 cytokine-driven RSV vaccine-mediated enhanced disease. [ABSTRACT FROM AUTHOR]

Published
2015
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11. Reply: To PMID 21901859.

Author

Brand HK, Hermans P, Warris A, and Borm G

Subjects
Female, Humans, Male, Bronchiolitis virology, Picornaviridae Infections diagnosis, Respiratory Syncytial Virus Infections diagnosis
Published
2013
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