Inside Precision Medicine
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Analyzing the plasma proteins of patients with sepsis can provide information on its severity and prognosis, researchers report.
Their findings highlight how affordable, high-throughput proteomics using mass spectrometry (MS) can map the plasma proteome and flag up differences in patient responses.
The study, in Science Translational Medicine, identified three clusters of sepsis patients from their plasma proteomes that were indicative of their response state, disease severity and outcomes.
Assignment to these different clusters changed for a given patient over time, suggesting it could be useful for therapeutic intervention and for monitoring disease progression.
“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 and moving toward a more precision medicine approach that may also be applicable to other disease states,” summarized Julian Knight, PhD, who runs a genomics lab at the University of Oxford, and co-workers.
Knight and team studied the proteome of 2612 plasma samples from 1189 patients with sepsis, 149 patients with non-septic inflammation, 76 non-infected patients from intensive care units, and 152 healthy volunteers.
Using higher-throughput automated and robust methods for sample preparation alongside MS-based data acquisition and data analysis, they were able to analyze more than 2500 nondepleted blood plasma samples in a single batch using a single liquid chromatography–MS platform.
The researchers studied out how the proteome shifted over time during sepsis and compared this with leukocyte transcriptomics from a separate group of 649 patients to provide insights into the nature of the sepsis response and its differences.
They identified three subgroups of sepsis patients according to their proteome profile, which included one with greater disease severity and organ damage.
In particular, a protein set that included prostaglandin D2 synthase, beta 2 microglobulin, and complement factor D among other proteins correlated closely with clinical variables reflecting more severe illness, such as shock or renal failure.
A second set of proteins, which included apolipoprotein A-I, histidine-rich glycoprotein, kininogen-1, and vitronectin showed reduced levels in these cases.
“The sepsis plasma proteome reflects mechanisms underlying the dysregulated host response to infection as well as the wider consequences of organ dysfunction (reduced metabolism and excretion for example) and tissue injury,” the researchers concluded.
“Proteomics therefore provides an opportunity to identify aspects of pathogenesis together with measures of organ dysfunction and disease severity.”
News & FeaturesMass spectrometryPlasmaProteomicsSepsis
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