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
1
Centre International de Recherches Médicales
de Franceville, B.P. 769, Franceville,
Gabon
2
Centre d'Immunologie et de Biologie Parasitaire, INSERM
U 167, Institut Pasteur de Lille, 1 rue du Professeur Calmette
, 59019, Lille, France
3
Laboratoire Central d'Immunologie Cellulaire et Tissulaire,
CNRS U 625, hôpital de la Pitié-Salpétrière,
Paris, France
4
Fondation Marcel Mérieux, 17 rue
Bourgelat, 69002 ,Lyon,France
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.
