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Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients
- Sylvain Baize1,2,
- Eric M. Leroy1,
- M.-C. Georges-Courbot1,
- Monique Capron2,
- Joseph Lansoud-Soukate1,
- Patrice Debré3,
- Susan P. Fisher-Hoch4,
- Joseph B. McCormick5 &
- …
- Alain J. Georges1
Nature Medicinevolume 5, pages423–426 (1999)Cite this article
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Abstract
Ebola virus is very pathogenic in humans. It induces an acute hemorrhagic fever that leads to death in about 70% of patients1. We compared the immune responses of patients who died from Ebola virus disease with those who survived during two large outbreaks in 1996 in Gabon. In survivors, early and increasing levels of IgG, directed mainly against the nucleoprotein and the 40-kDa viral protein, were followed by clearance of circulating viral antigen and activation of cytotoxic T cells, which was indicated by the upregulation of FasL, perforin, CD28 and gamma interferon mRNA in peripheral blood mononuclear cells. In contrast, fatal infection was characterized by impaired humoral responses, with absent specific IgG and barely detectable IgM. Early activation of T cells, indicated by mRNA patterns in peripheral blood mononuclear cells and considerable release of gamma interferon in plasma, was followed in the days preceding death by the disappearance of T cell-related mRNA (including CD3 and CD8). DNA fragmentation in blood leukocytes and release of 41/7 nuclear matrix protein in plasma indicated that massive intravascular apoptosis proceeded relentlessly during the last 5 days of life. Thus, events very early in Ebola virus infection determine the control of viral replication and recovery or catastrophic illness and death.
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Acknowledgements
We are grateful to C. Tevi-Benissan and P. Tshipamba for their assistance on fieldwork, and A. Pendy, B. Pambo and P. Obiang for access to patient specimens. We also thank V.E. Volchkov, P.E. Rollin and T.G. Ksiazek for providing Ebola-specific reagents and for their assistance with western blot analysis and IgM detection. S.B. is supported by a grant from the Ministère de la Recherche et de l'Enseignement Supérieur (France). CIRMF is supported by the state of Gabon, ELF-Gabon and the Ministère de la Coopération Française.
Author information
S.B. and E.M.L. contributed equally to this work
Authors and Affiliations
Centre International de Recherches Médicales de Franceville, B.P. 769, Franceville, Gabon
Sylvain Baize, Eric M. Leroy, M.-C. Georges-Courbot, Joseph Lansoud-Soukate & Alain J. Georges
Centre d'Immunologie et de Biologie Parasitaire, INSERM U 167, Institut Pasteur de Lille, 1 rue du Professeur Calmette , Lille, 59019, France
Sylvain Baize & Monique Capron
Laboratoire Central d'Immunologie Cellulaire et Tissulaire, CNRS U 625, hôpital de la Pitié-Salpétrière, Paris,, France
Patrice Debré
Fondation Marcel Mérieux, 17 rue Bourgelat, Lyon, 69002, France
Susan P. Fisher-Hoch
Pasteur/Mérieux/Connaught, 1541 avenue Marcel Mérieux, Marcy l'Etoile , 69260, France
Joseph B. McCormick
- Sylvain Baize
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- Eric M. Leroy
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- M.-C. Georges-Courbot
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- Monique Capron
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- Joseph Lansoud-Soukate
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- Patrice Debré
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- Susan P. Fisher-Hoch
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- Joseph B. McCormick
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- Alain J. Georges
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Baize, S., Leroy, E., Georges-Courbot, MC.et al. Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients.Nat Med5, 423–426 (1999). https://doi.org/10.1038/7422
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