Studying sepsis with protein patterns

A Swedish research team, led by brothers Johan, Erik and Lars Malmström, has developed a way to measure hundreds of proteins in a single blood sample, using these protein patterns to determine the severity of sepsis (blood poisoning) in individual patients. Their method has been published in the journal Nature Communications.

Caused by bacterial infection, sepsis is a condition in which the immune system starts to react erroneously in different ways. However, it is often difficult to diagnose because its symptoms — including high breathing rate, fever, rapid pulse, pain and confusion — occur in milder conditions as well. This is particularly problematic as the disease can progress very quickly, becoming fatal in just a few hours, and there is still much we don't know about it.

“Why do not all patients react the same way?" questioned Erik Malmström, a medical intern from Lund University. “Why do some organs suffer the most damage in some patients and not in others? Do different bacteria cause the disease to progress? Can you divide patients into different subgroups, or bacteria, or does each new combination of patients and bacteria lead to a specific form of sepsis?"

Now, the Malmström brothers and their colleagues at Lund University are measuring proteins to determine which organs have been damaged in sepsis sufferers. The team has already been able to map the majority of all proteins that can be found in vital organs such as the heart, lung, liver, spleen and blood vessels, and listed which proteins are specific to each specific organ.

“The method provides an understanding of the molecular events that take place during the course of a disease, and the possibility, using the same analysis, to study how different organs are affected," said Erik.

“If you see in a blood sample that the amount of proteins from a specific organ increases, it indicates damage to this organ," he continued. Erik's brother Johan, a biomedical scientist at Lund University, added, “We use the blood as a mirror reflecting what happens in the body."

The researchers have so far conducted their studies on animals but are now moving on to human tissue. Through a collaboration with surgeons at Skåne University Hospital, they have obtained samples of healthy tissue from all organs concerned. Protein patterns of these samples can then be compared with the corresponding tissue in sepsis patients.

“Protein mapping like this has never been done before," said Johan.

The group's study could eventually be used to select proteins that can serve as biomarkers for different aspects of sepsis. Fellow Lund University researcher Adam Linder has already begun to develop a diagnostic method based on the protein HB, which is emitted from the white blood cells and reflects the risk of hypotension.

“The method can also be applied to other diseases for studying how pathological changes in various organs are reflected in a blood sample," said Johan.

Image caption: Researchers Erik and Johan Malmström. Image credit: Ingela Björck.

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