The Role of Immune Semaphorins in Sepsis-A Prospective Cohort Study

In sepsis, a balanced pro-inflammatory and anti-inflammatory response results in the bacterial clearance and resolution of inflammation, promoting clinical recovery and survival. Semaphorins, a large family of secreted and membrane-bound glycoproteins, are newly recognized biomarkers and therapeutic targets in immunological and neoplastic disorders. Although semaphorins might also be a crucial part of host defense responses to infection, their role in sepsis is yet to be determined. This study aimed to analyze the association of serum semaphorin concentrations with sepsis severity and outcomes. Serum semaphorin concentrations (SEMA3A, SEMA3C, SEMA3F, SEMA4D, and SEMA7A) were measured in 115 adult patients with community-acquired sepsis and 50 healthy controls. While SEMA3A was decreased, SEMA3C, SEMA3F, SEMA4D, and SEMA7A were increased in sepsis patients. All analyzed SEMA showed good accuracy in identifying patients with sepsis. SEMA kinetics were related to sepsis complications; SEMA3A, SEMA3C, SEMA3F, and SEMA4D with respiratory failure; SEMA3C and SEMA7A with acute kidney injury; and SEMA3C and SEMA3F were related to septic shock. Importantly, SEMA3A, SEMA3C, SEMA4D, and SEMA7A were associated with 28-day mortality. In conclusion, we provide evidence that semaphorins are associated with sepsis course and outcomes.