Macrophage Activation Marker Soluble CD163 Associated with Fatal and Severe Ebola Virus Disease in Humans1

Emerg Infect Dis. 2019 Feb;25(2):290-298. doi: 10.3201/eid2502.181326.

Abstract

Ebola virus disease (EVD) is associated with elevated cytokine levels, and hypercytokinemia is more pronounced in fatal cases. This type of hyperinflammatory state is reminiscent of 2 rheumatologic disorders known as macrophage activation syndrome and hemophagocytic lymphohistiocytosis, which are characterized by macrophage and T-cell activation. An evaluation of 2 cohorts of patients with EVD revealed that a marker of macrophage activation (sCD163) but not T-cell activation (sCD25) was associated with severe and fatal EVD. Furthermore, substantial immunoreactivity of host tissues to a CD163-specific antibody, predominantly in areas of extensive immunostaining for Ebola virus antigens, was observed in fatal cases. These data suggest that host macrophage activation contributes to EVD pathogenesis and that directed antiinflammatory therapies could be beneficial in the treatment of EVD.

Keywords: CD163; Ebola; Ebola virus; Ebola virus disease; HLH; MAS; T cells; activation marker; hemophagocytic lymphohistiocytosis; humans; hyperferritinemia; hypertriglyceridemia; inflammation; macrophage; macrophage activation syndrome; sCD163; sCD25; severe disease; viruses; zoonoses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antigens, CD / blood*
  • Antigens, Differentiation, Myelomonocytic / blood*
  • Biomarkers
  • Ebolavirus / immunology*
  • Hemorrhagic Fever, Ebola / blood*
  • Hemorrhagic Fever, Ebola / diagnosis
  • Hemorrhagic Fever, Ebola / immunology*
  • Hemorrhagic Fever, Ebola / virology
  • Humans
  • Immunoassay
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Liver / immunology
  • Liver / metabolism
  • Liver / pathology
  • Macrophage Activation / immunology*
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Receptors, Cell Surface / blood*

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • CD163 antigen
  • Receptors, Cell Surface