Analyzing the plasma proteins of patients with sepsis can provide critical insights into the severity and prognosis of the condition, researchers report. Their findings demonstrate how affordable, high-throughput proteomics using mass spectrometry (MS) can effectively map the plasma proteome, revealing differences in patient responses.

The study, published in Science Translational Medicine, identified three distinct clusters of sepsis patients based on their plasma proteomes. These clusters were indicative of the patients’ response states, disease severity, and outcomes. The researchers found that a patient’s assignment to a particular cluster could change over time, suggesting potential applications for therapeutic intervention and disease progression monitoring.

“Our study shows the feasibility and informativeness of high-throughput proteomics using MS as part of a multimodal tool kit for understanding the nature of our individual response to severe infection,” summarized Julian Knight, PhD, who leads a genomics lab at the University of Oxford. This approach represents a move toward precision medicine that could be applicable to other disease states as well.

Knight and his team analyzed the proteomes of 2,612 plasma samples from 1,189 patients with sepsis, 149 patients with non-septic inflammation, 76 non-infected intensive care unit patients, and 152 healthy volunteers. Using high-throughput, automated methods for sample preparation and MS-based data acquisition and analysis, they were able to examine over 2,500 non-depleted blood plasma samples in a single batch on a single liquid chromatography–MS platform.

The researchers observed how the proteome shifted over time in sepsis patients and compared this with leukocyte transcriptomics from a separate group of 649 patients. This comparison provided deeper insights into the sepsis response and its variations.

The study identified three subgroups of sepsis patients according to their proteome profiles. One subgroup showed greater disease severity and organ damage. Specific proteins, such as prostaglandin D2 synthase, beta-2 microglobulin, and complement factor D, closely correlated with clinical variables reflecting severe illness, including shock and renal failure. Another set of proteins, including apolipoprotein A-I, histidine-rich glycoprotein, kininogen-1, and vitronectin, showed reduced levels in these severe cases.

“The sepsis plasma proteome reflects mechanisms underlying the dysregulated host response to infection, as well as the broader consequences of organ dysfunction and tissue injury,” the researchers concluded. “Proteomics provides an opportunity to identify aspects of pathogenesis alongside measures of organ dysfunction and disease severity.”

This research highlights the potential of high-throughput proteomics using MS to revolutionize the understanding and management of sepsis. By providing a detailed map of the plasma proteome, this approach could lead to more precise diagnostics, better monitoring of disease progression.

By Impact Lab