Confounder-Adjusted Plasma Proteomics Identify Robust Protein Signatures in Sepsis Across Two Independent Perioperative Control Cohorts

Sepsis is the primary driver of mortality in intensive care units. Researchers compared 343 sepsis patients with two independent control cohorts of 73 and 75 patients sampled before and after surgery. Plasma analysis was performed using mass spectrometry adjusted for age, sex, and specific comorbidities. Renal comorbidities had the strongest impact on the plasma proteome and affected sepsis-associated proteins including Cystatin-C and Beta-2-microglobulin. Eleven proteins were robustly associated with sepsis, including the less well-characterized Beta-1,4-galactosyltransferase 1. Classifiers performed very well except against control patients on day 3 after surgery, when sterile inflammation peaked. The results suggest that sepsis, comorbidities, and sterile inflammation may alter the same acute phase and renal proteins, differing in magnitude rather than in the type of response.