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Immune parameters and outcomes during Ebola virus disease
Stéphanie Reynard, … , Jimmy Mullaert, Sylvain Baize
Stéphanie Reynard, … , Jimmy Mullaert, Sylvain Baize
Published January 10, 2019
Citation Information: JCI Insight. 2019;4(1):e125106. https://doi.org/10.1172/jci.insight.125106.
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Clinical Medicine Infectious disease Virology

Immune parameters and outcomes during Ebola virus disease

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Abstract

BACKGROUND. The West African Ebola virus epidemic from 2014–2016 highlighted the lack of knowledge about the pathogenicity of the virus and the factors responsible for outcome. A performant and rapid diagnosis is of crucial importance, as is overcoming the difficulty of providing high-quality patient management during such an extensive outbreak. Here, we propose to study the role of the immune mediators during Ebola virus disease and to define some molecules of importance in the outcome. METHODS. Plasma from Guinean patients sampled during the outbreak were analyzed using RT-qPCR, magnetic bead assay, ELISA, and high-quality statistical analyses. We also performed a transcriptomic analysis in leukocytes samples. Therefore, we deeply characterized the immune responses involved in Ebola virus disease. RESULTS. We evaluated the immune patterns depending on the outcome of the disease. Survivors presented an efficient and well-balanced immune response, whereas fatalities were characterized by an intense inflammatory response, overexpression of multiple cytokines, and a “chemokine storm.” The plasma concentration of most of the parameters tested increased until death. Statistical analyses also allowed us to define a panel of markers highly predictive of outcome. CONCLUSION. The immune response observed in fatalities was highly similar to that characterizing septic shock syndrome. Our results suggest that immune responses can play a major pathogenic role during severe Ebola virus infection and argue in favor of therapeutic approaches that act on both viral replication and the induction of shock syndrome. FUNDING. French Ministry of Foreign Affairs, the Agence Française de Développement, and the Institut Pasteur.

Authors

Stéphanie Reynard, Alexandra Journeaux, Emilie Gloaguen, Justine Schaeffer, Hugo Varet, Natalia Pietrosemoli, Mathieu Mateo, Nicolas Baillet, Cédric Laouenan, Hervé Raoul, Jimmy Mullaert, Sylvain Baize

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Figure 7

Soluble forms of cytotoxic molecules involved in T cell response were assayed using magnetic bead multiplex panels.

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Soluble forms of cytotoxic molecules involved in T cell response were as...
(A) Samples were analyzed, and data are presented as in Figure 4, A and C; Figure 5, A and C; and Figure 6A, with fatal cases (n = 44), survivors (n = 58), and controls (n = 15). (B) The box plots represent all time points combined for each group, with only the first sample for each patient analyzed, as in Figure 4, B and D; Figure 5B; and Figure 6A (fatal cases [Fat], n = 42; survivors [Surv], n = 33; controls [Ctrl], n = 15). The boxes define the 25th and 75th percentiles, with a line at the median; errors bars define the 10th and 90th percentile; and dots define the 5th and 95th percentile. The P values were determined by a Wilcoxon rank-sum test and are indicated in the box plots.

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