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646. Activated Macrophages as Pathogenesis Factors in Ebola Virus Disease in Humans

BACKGROUND: Ebola virus disease (EVD) is associated with elevated cytokine levels that are more pronounced in fatal cases. This type of hyperinflammatory state is reminiscent of other inflammatory disorders, such as macrophage activation syndrome (MAS) or hemophagocytic lymphohistiocytosis (HLH). Th...

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Autores principales: McElroy, Anita, Shrivastava-Ranjan, Punya, Harmon, Jessica, Martines, Roosecelis, Silva-Flannery, Luciana, Flietstra, Timothy, Kraft, Colleen, Mehta, Aneesh K, III, G Marshall Lyon, Varkey, Jay, Ribner, Bruce, Nichol, Stuart, Zaki, Sherif, Spiropoulou, Christina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254321/
http://dx.doi.org/10.1093/ofid/ofy210.653
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author McElroy, Anita
Shrivastava-Ranjan, Punya
Harmon, Jessica
Martines, Roosecelis
Silva-Flannery, Luciana
Flietstra, Timothy
Kraft, Colleen
Mehta, Aneesh K
III, G Marshall Lyon
Varkey, Jay
Ribner, Bruce
Nichol, Stuart
Zaki, Sherif
Spiropoulou, Christina
author_facet McElroy, Anita
Shrivastava-Ranjan, Punya
Harmon, Jessica
Martines, Roosecelis
Silva-Flannery, Luciana
Flietstra, Timothy
Kraft, Colleen
Mehta, Aneesh K
III, G Marshall Lyon
Varkey, Jay
Ribner, Bruce
Nichol, Stuart
Zaki, Sherif
Spiropoulou, Christina
author_sort McElroy, Anita
collection PubMed
description BACKGROUND: Ebola virus disease (EVD) is associated with elevated cytokine levels that are more pronounced in fatal cases. This type of hyperinflammatory state is reminiscent of other inflammatory disorders, such as macrophage activation syndrome (MAS) or hemophagocytic lymphohistiocytosis (HLH). These are both part of a spectrum of rheumatologic phenomena characterized by both macrophage and T-cell activation. These disorders can be secondary to infection, malignancy, underlying rheumatologic disorder, or, paradoxically, immune deficiency. METHODS: Two cohorts of EVD patients were evaluated with respect to common plasma markers of HLH/MAS. Immunohistochemistry was used to evaluate tissue macrophages and viral antigens in various tissues from fatal cases of EVD. RESULTS: Neither fibrinogen nor soluble IL-2 receptor were significantly different between fatal and nonfatal cases. However, elevated levels of triglycerides, ferritin and sCD163, a marker of macrophage activation were noted in patients with EVD and they correlated with disease severity and a fatal outcome. Furthermore, significant immunoreactivity for CD163 + cells in host tissues was observed in fatal cases, predominantly in areas of extensive immunostaining for EBOV antigens. CONCLUSION: These data suggest that host macrophage activation contributes to EVD pathogenesis and that directed anti-inflammatory therapies could be beneficial in the treatment of EVD. DISCLOSURES: All authors: No reported disclosures.
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spelling pubmed-62543212018-11-28 646. Activated Macrophages as Pathogenesis Factors in Ebola Virus Disease in Humans McElroy, Anita Shrivastava-Ranjan, Punya Harmon, Jessica Martines, Roosecelis Silva-Flannery, Luciana Flietstra, Timothy Kraft, Colleen Mehta, Aneesh K III, G Marshall Lyon Varkey, Jay Ribner, Bruce Nichol, Stuart Zaki, Sherif Spiropoulou, Christina Open Forum Infect Dis Abstracts BACKGROUND: Ebola virus disease (EVD) is associated with elevated cytokine levels that are more pronounced in fatal cases. This type of hyperinflammatory state is reminiscent of other inflammatory disorders, such as macrophage activation syndrome (MAS) or hemophagocytic lymphohistiocytosis (HLH). These are both part of a spectrum of rheumatologic phenomena characterized by both macrophage and T-cell activation. These disorders can be secondary to infection, malignancy, underlying rheumatologic disorder, or, paradoxically, immune deficiency. METHODS: Two cohorts of EVD patients were evaluated with respect to common plasma markers of HLH/MAS. Immunohistochemistry was used to evaluate tissue macrophages and viral antigens in various tissues from fatal cases of EVD. RESULTS: Neither fibrinogen nor soluble IL-2 receptor were significantly different between fatal and nonfatal cases. However, elevated levels of triglycerides, ferritin and sCD163, a marker of macrophage activation were noted in patients with EVD and they correlated with disease severity and a fatal outcome. Furthermore, significant immunoreactivity for CD163 + cells in host tissues was observed in fatal cases, predominantly in areas of extensive immunostaining for EBOV antigens. CONCLUSION: These data suggest that host macrophage activation contributes to EVD pathogenesis and that directed anti-inflammatory therapies could be beneficial in the treatment of EVD. DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2018-11-26 /pmc/articles/PMC6254321/ http://dx.doi.org/10.1093/ofid/ofy210.653 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
McElroy, Anita
Shrivastava-Ranjan, Punya
Harmon, Jessica
Martines, Roosecelis
Silva-Flannery, Luciana
Flietstra, Timothy
Kraft, Colleen
Mehta, Aneesh K
III, G Marshall Lyon
Varkey, Jay
Ribner, Bruce
Nichol, Stuart
Zaki, Sherif
Spiropoulou, Christina
646. Activated Macrophages as Pathogenesis Factors in Ebola Virus Disease in Humans
title 646. Activated Macrophages as Pathogenesis Factors in Ebola Virus Disease in Humans
title_full 646. Activated Macrophages as Pathogenesis Factors in Ebola Virus Disease in Humans
title_fullStr 646. Activated Macrophages as Pathogenesis Factors in Ebola Virus Disease in Humans
title_full_unstemmed 646. Activated Macrophages as Pathogenesis Factors in Ebola Virus Disease in Humans
title_short 646. Activated Macrophages as Pathogenesis Factors in Ebola Virus Disease in Humans
title_sort 646. activated macrophages as pathogenesis factors in ebola virus disease in humans
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254321/
http://dx.doi.org/10.1093/ofid/ofy210.653
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