Proteomic exosome evaluation in patients with sepsis and septic shock compared to healthy controls
Jaehne AK, Cheung WL, Chen Y, Poisson L, Chopp M, Zhang Z, Buller B, Osobamiro O, Rivers E, and Morris D. Proteomic exosome evaluation in patients with sepsis and septic shock compared to healthy controls. Crit Care Med 2019; 47(1).
Crit Care Med
Learning Objectives: Sepsis is the body's response to infectious agents. The understanding of the pathogenic mechanisms leading to multi-organ dysfunction and death in up to 45% of septic patients is limited. Membrane nano-sized vesicles (exosomes) are important carriers of intracellular information containing mRNA and proteins. This exosomes may contribute to the pathogenesis of organ dysfunction and to-date have not sufficiently evaluated. We hypothesize that plasma exosome proteomic profiles of septic patients differ from healthy controls. Methods: Pilot exploratory evaluation of plasma exosome proteomic profiles for 2 female septic patients, 2 female and one male healthy control. Plasma exosomes were isolated using Invitrogen Total Exosome Isolation Kit. Exosome proteomic profiles were analyzed using standard preparation with reversed phase chromatography, ionization and fusion mass spectroscopy followed by data analysis using Proteome Discoverer. Statistical analysis was performed using correlation, heat map (HMA) and principal component analysis (PCA) along with linear modeling using the limma package from Bioconductor (V3.34.0). Results: Mass spectroscopy quantified 313 proteins. Using results of HMA and PCA we were able to conclude that the exosome proteomic profiles of septic patients were similar to each other and that these profiles were similar in healthy controls. Linear modeling identified 60 differently expressed proteins in septic patients (p-value ≤0.05). After adjusting for multiple comparison using False-Discovery-Rate methods, 7 proteins remained significantly different (q value ≤0.1). These proteins are serum amyloid A-2 (AA2), coagulation factor 8 (FA8), immunoglobulin heavy constant Δ (IGHD), immunoglobulin κ variable 1-8 (KV108), von Willebrand factor (VWF), serum amyloid A-4 (SAA4), and cytoplasmatic Actin1 (ACTB). KV108 and ACTB are more abundant in healthy controls while the other 5 proteins in septic patients. Conclusions: Plasma proteomic exosome profiles from septic patients differ from healthy controls. Future research should address how exosomes contribute to the pathogenesis of multi-organ dysfunction in sepsis.