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

Choby JE, Monteith AJ, Himmel LE, Margaritis P, Shirey-Rice JK, Pruijssers A, Jerome RN, Pulley J, Skaar EP
Infect Immun. 2019 87 (5)

PMID: 30782860 · PMCID: PMC6479028 · DOI:10.1128/IAI.00031-19

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 infection, suggesting that factor X plays a role in the immune response to 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 infection.

Copyright © 2019 American Society for Microbiology.

MeSH Terms (11)

Acinetobacter baumannii Acinetobacter Infections Animals Disease Models, Animal Factor X Host-Pathogen Interactions Humans Mice Mice, Inbred C57BL Phenotype Polymorphism, Genetic

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