Investigating the biomarker potential of circulating small extracellular vesicles in patients presenting with sepsis.

Abstract

Sepsis is defined as an inflammatory disorder caused by a dysregulated immune response to infection, affecting approximately 48.9 million people globally. The complex and multifaceted pathophysiology of sepsis complicates clinical diagnosis, management and treatment. Without a validated gold standard for diagnosis, definitive biomarkers are critical. Recently, small extracellular vesicles (sEVs) and exosomes1 have emerged as promising biomarkers of disease, owing to their role in intercellular communication. Therefore, the present study has evaluated the use of sEVs as possible biomarkers for sepsis. The approach included providing a theoretical framework surrounding sEVs, their role in sepsis pathophysiology and the potential these sEVs have as diagnostic, prognostic and therapeutic tools for sepsis. This led to the evaluation of commonly used surface markers for identifying extracellular vesicles using a multi-level, automated and precise platform. We identified an abundance of CD63, CD81 and CD9 positive particles in sepsis patients. Interestingly, the data provided distinct colocalization patterns which are abundant in sepsis patients. Our study highlighted that the CD63/CD9 colocalization may be of increasing interest in exploring the potential of these vesicles as biomarkers for sepsis. Furthermore, developing biomarkers for sepsis has become increasingly difficult due to the presence of co-morbidities. These co-morbidities further complicate the pathophysiology of sepsis, increasing the mortality rate and the risk of developing organ failure. Additionally, previous studies confirm a vast array of surface markers on the membrane of sEVs. These markers have roles in protein-protein interactions and target cell signalling. We then, further investigated the surface marker profiles in 4 cohorts (viz. healthy controls, hypertension, sepsis patients with no pre-existing co-morbidities and sepsis patients with previously diagnosed hypertension). In doing so, we identified specific surface marker profiles of sepsis and hypertension when compared to healthy controls or the other pathological states. These surface marker profiles could aid in the further understanding of sepsis pathophysiology and the role sEVs play therein. This study highlights that sEVs and the identified surface marker profiles could be exploited in the interest of biomarker development for sepsis.