Definition of erythroid cell‐positive blood transcriptome phenotypes associated with severe respiratory syncytial virus infection
Abstract Biomarkers to assess the risk of developing severe respiratory syncytial virus (RSV) infection are needed. We conducted a meta‐analysis of 490 unique profiles from six public RSV blood transcriptome datasets. A repertoire of 382 well‐characterized transcriptional modules was used to define...
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doaj-1b61fc5665cc4b83bcb5d689d4936bf52021-05-07T14:40:31ZengWileyClinical and Translational Medicine2001-13262020-12-01108n/an/a10.1002/ctm2.244Definition of erythroid cell‐positive blood transcriptome phenotypes associated with severe respiratory syncytial virus infectionDarawan Rinchai0Matthew C. Altman1Oceane Konza2Signe Hässler3Federica Martina4Mohammed Toufiq5Mathieu Garand6Basirudeen Syed Ahamed Kabeer7Karolina Palucka8Asuncion Mejias9Octavio Ramilo10Davide Bedognetti11Encarnita Mariotti‐Ferrandiz12David Klatzmann13Damien Chaussabel14Sidra Medicine Doha QatarBenaroya Research Institute Seattle WashingtonBiotherapy (CIC‐BTi) and Inflammation‐Immunopathology‐Biotherapy Department (i2B) AP‐HP, Hôpital Pitié‐Salpêtrière Paris FranceBiotherapy (CIC‐BTi) and Inflammation‐Immunopathology‐Biotherapy Department (i2B) AP‐HP, Hôpital Pitié‐Salpêtrière Paris FranceBiotherapy (CIC‐BTi) and Inflammation‐Immunopathology‐Biotherapy Department (i2B) AP‐HP, Hôpital Pitié‐Salpêtrière Paris FranceSidra Medicine Doha QatarSidra Medicine Doha QatarSidra Medicine Doha QatarJackson Laboratory for Genomic Medicine Farmington ConnecticutDivision of Infectious Diseases Nationwide Children's Hospital Columbus OhioDivision of Infectious Diseases Nationwide Children's Hospital Columbus OhioSidra Medicine Doha QatarImmunology‐Immunopathology‐Immunotherapy (i3) Sorbonne Université INSERM Paris FranceBiotherapy (CIC‐BTi) and Inflammation‐Immunopathology‐Biotherapy Department (i2B) AP‐HP, Hôpital Pitié‐Salpêtrière Paris FranceSidra Medicine Doha QatarAbstract Biomarkers to assess the risk of developing severe respiratory syncytial virus (RSV) infection are needed. We conducted a meta‐analysis of 490 unique profiles from six public RSV blood transcriptome datasets. A repertoire of 382 well‐characterized transcriptional modules was used to define dominant host responses to RSV infection. The consolidated RSV cohort was stratified according to four traits: “interferon response” (IFN), “neutrophil‐driven inflammation” (Infl), “cell cycle” (CC), and “erythrocytes” (Ery). We identified eight prevalent blood transcriptome phenotypes, of which three Ery+ phenotypes comprised higher proportions of patients requiring intensive care. This finding confirms on a larger scale data from one of our earlier reports describing an association between an erythrocyte signature and RSV disease severity. Further contextual interpretation made it possible to associate this signature with immunosuppressive states (late stage cancer, pharmacological immunosuppression), and with a population of fetal glycophorin A+ erythroid precursors. Furthermore, we posit that this erythrocyte cell signature may be linked to a population of immunosuppressive erythroid cells previously described in the literature, and that overabundance of this cell population in RSV patients may underlie progression to severe disease. These findings outline potential priority areas for biomarker development and investigations into the immune biology of RSV infection. The approach that we developed and employed here should also permit to delineate prevalent blood transcriptome phenotypes in other settings.https://doi.org/10.1002/ctm2.244 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Darawan Rinchai Matthew C. Altman Oceane Konza Signe Hässler Federica Martina Mohammed Toufiq Mathieu Garand Basirudeen Syed Ahamed Kabeer Karolina Palucka Asuncion Mejias Octavio Ramilo Davide Bedognetti Encarnita Mariotti‐Ferrandiz David Klatzmann Damien Chaussabel |
spellingShingle |
Darawan Rinchai Matthew C. Altman Oceane Konza Signe Hässler Federica Martina Mohammed Toufiq Mathieu Garand Basirudeen Syed Ahamed Kabeer Karolina Palucka Asuncion Mejias Octavio Ramilo Davide Bedognetti Encarnita Mariotti‐Ferrandiz David Klatzmann Damien Chaussabel Definition of erythroid cell‐positive blood transcriptome phenotypes associated with severe respiratory syncytial virus infection Clinical and Translational Medicine |
author_facet |
Darawan Rinchai Matthew C. Altman Oceane Konza Signe Hässler Federica Martina Mohammed Toufiq Mathieu Garand Basirudeen Syed Ahamed Kabeer Karolina Palucka Asuncion Mejias Octavio Ramilo Davide Bedognetti Encarnita Mariotti‐Ferrandiz David Klatzmann Damien Chaussabel |
author_sort |
Darawan Rinchai |
title |
Definition of erythroid cell‐positive blood transcriptome phenotypes associated with severe respiratory syncytial virus infection |
title_short |
Definition of erythroid cell‐positive blood transcriptome phenotypes associated with severe respiratory syncytial virus infection |
title_full |
Definition of erythroid cell‐positive blood transcriptome phenotypes associated with severe respiratory syncytial virus infection |
title_fullStr |
Definition of erythroid cell‐positive blood transcriptome phenotypes associated with severe respiratory syncytial virus infection |
title_full_unstemmed |
Definition of erythroid cell‐positive blood transcriptome phenotypes associated with severe respiratory syncytial virus infection |
title_sort |
definition of erythroid cell‐positive blood transcriptome phenotypes associated with severe respiratory syncytial virus infection |
publisher |
Wiley |
series |
Clinical and Translational Medicine |
issn |
2001-1326 |
publishDate |
2020-12-01 |
description |
Abstract Biomarkers to assess the risk of developing severe respiratory syncytial virus (RSV) infection are needed. We conducted a meta‐analysis of 490 unique profiles from six public RSV blood transcriptome datasets. A repertoire of 382 well‐characterized transcriptional modules was used to define dominant host responses to RSV infection. The consolidated RSV cohort was stratified according to four traits: “interferon response” (IFN), “neutrophil‐driven inflammation” (Infl), “cell cycle” (CC), and “erythrocytes” (Ery). We identified eight prevalent blood transcriptome phenotypes, of which three Ery+ phenotypes comprised higher proportions of patients requiring intensive care. This finding confirms on a larger scale data from one of our earlier reports describing an association between an erythrocyte signature and RSV disease severity. Further contextual interpretation made it possible to associate this signature with immunosuppressive states (late stage cancer, pharmacological immunosuppression), and with a population of fetal glycophorin A+ erythroid precursors. Furthermore, we posit that this erythrocyte cell signature may be linked to a population of immunosuppressive erythroid cells previously described in the literature, and that overabundance of this cell population in RSV patients may underlie progression to severe disease. These findings outline potential priority areas for biomarker development and investigations into the immune biology of RSV infection. The approach that we developed and employed here should also permit to delineate prevalent blood transcriptome phenotypes in other settings. |
url |
https://doi.org/10.1002/ctm2.244 |
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