A Phenome-Wide Association Study Uncovers a Pathological Role of Coagulation Factor X during Acinetobacter baumannii Infection

Infect Immun. 2019 Apr 23;87(5):e00031-19. doi: 10.1128/IAI.00031-19. Print 2019 Mar.


Coagulation and inflammation are interconnected, suggesting that coagulation plays a key role in the inflammatory response to pathogens. A phenome-wide association study (PheWAS) was used to identify clinical phenotypes of patients with a polymorphism in coagulation factor X. Patients with this single nucleotide polymorphism (SNP) were more likely to be hospitalized with hemostatic and infection-related disorders, suggesting that factor X contributes to the immune response to infection. To investigate this, we modeled infections by human pathogens in a mouse model of factor X deficiency. Factor X-deficient mice were protected from systemic Acinetobacter baumannii infection, suggesting that factor X plays a role in the immune response to A. baumannii Factor X deficiency was associated with reduced cytokine and chemokine production and alterations in immune cell population during infection: factor X-deficient mice demonstrated increased abundance of neutrophils, macrophages, and effector T cells. Together, these results suggest that factor X activity is associated with an inefficient immune response and contributes to the pathology of A. baumannii infection.

Keywords: Acinetobacter; PheWAS; coagulation; innate immunity.

Publication types

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

MeSH terms

  • Acinetobacter Infections / immunology*
  • Acinetobacter Infections / physiopathology*
  • Acinetobacter baumannii / immunology*
  • Animals
  • Disease Models, Animal
  • Factor X / genetics*
  • Factor X / immunology*
  • Host-Pathogen Interactions / genetics*
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Phenotype
  • Polymorphism, Genetic


  • Factor X