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Whole blood RNA sequencing reveals a unique transcriptomic profile in patients with ARDS following hematopoietic stem cell transplantation

BACKGROUND: The acute respiratory distress syndrome (ARDS) is characterized by the acute onset of hypoxemia and bilateral lung infiltrates in response to an inciting event, and is associated with high morbidity and mortality. Patients undergoing allogeneic hematopoietic stem cell transplantation (HS...

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Autores principales: Englert, Joshua A., Cho, Michael H., Lamb, Andrew E., Shumyatcher, Maya, Barragan-Bradford, Diana, Basil, Maria C., Higuera, Angelica, Isabelle, Colleen, Vera, Mayra Pinilla, Dieffenbach, Paul B., Fredenburgh, Laura E., Kang, Joyce B., Bhatt, Ami S., Antin, Joseph H., Ho, Vincent T., Soiffer, Robert J., Howrylak, Judie A., Himes, Blanca E., Baron, Rebecca M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341764/
https://www.ncbi.nlm.nih.gov/pubmed/30665420
http://dx.doi.org/10.1186/s12931-019-0981-6
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author Englert, Joshua A.
Cho, Michael H.
Lamb, Andrew E.
Shumyatcher, Maya
Barragan-Bradford, Diana
Basil, Maria C.
Higuera, Angelica
Isabelle, Colleen
Vera, Mayra Pinilla
Dieffenbach, Paul B.
Fredenburgh, Laura E.
Kang, Joyce B.
Bhatt, Ami S.
Antin, Joseph H.
Ho, Vincent T.
Soiffer, Robert J.
Howrylak, Judie A.
Himes, Blanca E.
Baron, Rebecca M.
author_facet Englert, Joshua A.
Cho, Michael H.
Lamb, Andrew E.
Shumyatcher, Maya
Barragan-Bradford, Diana
Basil, Maria C.
Higuera, Angelica
Isabelle, Colleen
Vera, Mayra Pinilla
Dieffenbach, Paul B.
Fredenburgh, Laura E.
Kang, Joyce B.
Bhatt, Ami S.
Antin, Joseph H.
Ho, Vincent T.
Soiffer, Robert J.
Howrylak, Judie A.
Himes, Blanca E.
Baron, Rebecca M.
author_sort Englert, Joshua A.
collection PubMed
description BACKGROUND: The acute respiratory distress syndrome (ARDS) is characterized by the acute onset of hypoxemia and bilateral lung infiltrates in response to an inciting event, and is associated with high morbidity and mortality. Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk for ARDS. We hypothesized that HSCT patients with ARDS would have a unique transcriptomic profile identifiable in peripheral blood compared to those that did not undergo HSCT. METHODS: We isolated RNA from banked peripheral blood samples from a biorepository of critically ill ICU patients. RNA-Seq was performed on 11 patients with ARDS (5 that had undergone HSCT and 6 that had not) and 12 patients with sepsis without ARDS (5 that that had undergone HCST and 7 that had not). RESULTS: We identified 687 differentially expressed genes between ARDS and ARDS-HSCT (adjusted p-value < 0.01), including IFI44L, OAS3, LY6E, and SPATS2L that had increased expression in ARDS vs. ARDS-HSCT; these genes were not differentially expressed in sepsis vs sepsis-HSCT. Gene ontology enrichment analysis revealed that many differentially expressed genes were related to response to type I interferon. CONCLUSIONS: Our findings reveal significant differences in whole blood transcriptomic profiles of patients with non-HSCT ARDS compared to ARDS-HSCT patients and point toward different immune responses underlying ARDS and ARDS-HSCT that contribute to lung injury. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-019-0981-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-63417642019-01-24 Whole blood RNA sequencing reveals a unique transcriptomic profile in patients with ARDS following hematopoietic stem cell transplantation Englert, Joshua A. Cho, Michael H. Lamb, Andrew E. Shumyatcher, Maya Barragan-Bradford, Diana Basil, Maria C. Higuera, Angelica Isabelle, Colleen Vera, Mayra Pinilla Dieffenbach, Paul B. Fredenburgh, Laura E. Kang, Joyce B. Bhatt, Ami S. Antin, Joseph H. Ho, Vincent T. Soiffer, Robert J. Howrylak, Judie A. Himes, Blanca E. Baron, Rebecca M. Respir Res Research BACKGROUND: The acute respiratory distress syndrome (ARDS) is characterized by the acute onset of hypoxemia and bilateral lung infiltrates in response to an inciting event, and is associated with high morbidity and mortality. Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk for ARDS. We hypothesized that HSCT patients with ARDS would have a unique transcriptomic profile identifiable in peripheral blood compared to those that did not undergo HSCT. METHODS: We isolated RNA from banked peripheral blood samples from a biorepository of critically ill ICU patients. RNA-Seq was performed on 11 patients with ARDS (5 that had undergone HSCT and 6 that had not) and 12 patients with sepsis without ARDS (5 that that had undergone HCST and 7 that had not). RESULTS: We identified 687 differentially expressed genes between ARDS and ARDS-HSCT (adjusted p-value < 0.01), including IFI44L, OAS3, LY6E, and SPATS2L that had increased expression in ARDS vs. ARDS-HSCT; these genes were not differentially expressed in sepsis vs sepsis-HSCT. Gene ontology enrichment analysis revealed that many differentially expressed genes were related to response to type I interferon. CONCLUSIONS: Our findings reveal significant differences in whole blood transcriptomic profiles of patients with non-HSCT ARDS compared to ARDS-HSCT patients and point toward different immune responses underlying ARDS and ARDS-HSCT that contribute to lung injury. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-019-0981-6) contains supplementary material, which is available to authorized users. BioMed Central 2019-01-21 2019 /pmc/articles/PMC6341764/ /pubmed/30665420 http://dx.doi.org/10.1186/s12931-019-0981-6 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Englert, Joshua A.
Cho, Michael H.
Lamb, Andrew E.
Shumyatcher, Maya
Barragan-Bradford, Diana
Basil, Maria C.
Higuera, Angelica
Isabelle, Colleen
Vera, Mayra Pinilla
Dieffenbach, Paul B.
Fredenburgh, Laura E.
Kang, Joyce B.
Bhatt, Ami S.
Antin, Joseph H.
Ho, Vincent T.
Soiffer, Robert J.
Howrylak, Judie A.
Himes, Blanca E.
Baron, Rebecca M.
Whole blood RNA sequencing reveals a unique transcriptomic profile in patients with ARDS following hematopoietic stem cell transplantation
title Whole blood RNA sequencing reveals a unique transcriptomic profile in patients with ARDS following hematopoietic stem cell transplantation
title_full Whole blood RNA sequencing reveals a unique transcriptomic profile in patients with ARDS following hematopoietic stem cell transplantation
title_fullStr Whole blood RNA sequencing reveals a unique transcriptomic profile in patients with ARDS following hematopoietic stem cell transplantation
title_full_unstemmed Whole blood RNA sequencing reveals a unique transcriptomic profile in patients with ARDS following hematopoietic stem cell transplantation
title_short Whole blood RNA sequencing reveals a unique transcriptomic profile in patients with ARDS following hematopoietic stem cell transplantation
title_sort whole blood rna sequencing reveals a unique transcriptomic profile in patients with ards following hematopoietic stem cell transplantation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341764/
https://www.ncbi.nlm.nih.gov/pubmed/30665420
http://dx.doi.org/10.1186/s12931-019-0981-6
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