Endothelial activation and dysfunction in severe fever with thrombocytopenia syndrome

PLoS Negl Trop Dis. 2017 Aug 14;11(8):e0005746. doi: 10.1371/journal.pntd.0005746. eCollection 2017 Aug.

Abstract

Background: Pathogenesis of severe fever with thrombocytopenia syndrome (SFTS) has not been well described yet. Recent studies indicate that SFTSV could replicate in endothelial cells. Here we performed a case-control study to determine whether endothelial activation/dysfunction occurred in SFTSV infection and to identify the biomarkers reflecting endothelial dysfunction.

Methodology/principal findings: In a case-control study of 134 SFTS patients and 68 healthy controls, serum levels of plasminogen activator inhibitor 1, tissue plasminogen activator, P-selectin, platelet endothelial cell adhesion molecular, CD40 ligand, E-selectin, vascular endothelial growth factor A, serum amyloid antigen 1 (SAA-1) and vascular cell adhesion molecular 1 were significantly enhanced in the patients than the controls (all P<0.05), indicating the occurrence of endothelial activation/dysfunction in SFTS. The intercellular adhesion molecular 1 (ICAM-1) and SAA-1 at the convalescent phase were also significantly associated with severe patients, after adjusting for the potential confounders. The odds ratio was estimated to be 3.364 (95% CI 1.074-10.534) for ICAM-1, and 1.881 (95% CI 1.166-3.034) for SAA-1, respectively. Cutoff value of 1.1×107 pg/mL SAA-1 or 1.2×106 pg/mL ICAM-1 were found to have moderate power of predicting fatal cases.

Conclusions: The endothelial dysfunction may be one of the pathogenic mechanism of SFTS. The serum levels of ICAM-1 and SAA-1 might be used to predict adverse outcome.

MeSH terms

  • Biomarkers / blood*
  • Bunyaviridae Infections / physiopathology*
  • Bunyaviridae Infections / virology
  • Case-Control Studies
  • Endothelial Cells / physiology*
  • Endothelial Cells / virology*
  • Humans
  • Intercellular Adhesion Molecule-1 / blood*
  • Phlebovirus / physiology*
  • Serum Amyloid A Protein / analysis*

Substances

  • Biomarkers
  • SAA1 protein, human
  • Serum Amyloid A Protein
  • Intercellular Adhesion Molecule-1

Grants and funding

This work was supported by grants from the National Natural Science Foundation (No. 81473023 and 81703274), the State Key Laboratory of Pathogen and Biosecurity (Academy of Military Medical Science, SKLPBS1442) and the Youth Talent Support Program by the School of Public Health, Peking University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.