PheWAS uncovers a pathological role of coagulation Factor X during Acinetobacter baumannii infection.

Coagulation and inflammation are interconnected, suggesting 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 SNP were more likely to be hospitalized with hemostatic and infection-related disorders, suggesting 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 A. baumannii infection, suggesting 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.