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

ABSTRACT: 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.

SUBMITTER: Choby JE

PROVIDER: S-EPMC6479028 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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A Phenome-Wide Association Study Uncovers a Pathological Role of Coagulation Factor X during <i>Acinetobacter baumannii</i> Infection.

Choby Jacob E JE Monteith Andrew J AJ Himmel Lauren E LE Margaritis Paris P Shirey-Rice Jana K JK Pruijssers Andrea A Jerome Rebecca N RN Pulley Jill J Skaar Eric P EP

Infection and immunity 20190301 5

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 inves ...[more]

PMID: 30782860

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Dataset Information

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

Publications

A Phenome-Wide Association Study Uncovers a Pathological Role of Coagulation Factor X during <i>Acinetobacter baumannii</i> Infection.

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