Organ failure: Who gets hit?

25 July 2017

Interview with

Jo Shepherd, Queen Mary University of London

Every day thousands of people around the world suffer serious injuries from accidents. Many die at the scene, but a significant number survive the initial insult only to develop a fatal complication later called multiple organ dysfunction syndrome. But why do these victims die, and who's at risk? Chris Smith spoke to Jo Shepherd, a surgeon based in London…

Jo - We looked at the very early immune response to trauma, so major injury. This can include anything from being hit by a bus, being stabbed, falling from a height, so any physical injury to the body. There are about 50 patients a day day in the UK die from critical injuries such as these but, in those who survive, there’s a huge chance of developing what we call multiple organ dysfunction syndrome, which is essentially a failure of organs in the body including the heart, lungs, liver, kidneys, and brain. Even though they’ve not been directly injured the body’s immune response can become disrupted or exaggerated and we think that this causes organ dysfunction.

Chris - So you’d quite like to know who the people are who are at risk of developing that so you can anticipate it and then perhaps even stop it?

Jo - Exactly. It’s a huge imperative in modern medicine that we try and find out why these patients are developing multiple organ dysfunction and, therefore, we can try and figure out how we might be able to treat it.

Chris - How have you done it?

Jo - We took blood samples in the resuscitation room from 70 critically injured patients, so the first minutes to hours after injury. What we’ve done is try and study the immune cell composition within those blood samples, looking both at the numbers of different types of immune cell in the blood as well as the genes that might be affecting those immune cells.

Chris - And your rationale is that if you look at what the genes are, and you look at what the cells are, and you know which patients go on to develop this syndrome, you’re looking for a sort of cell and gene fingerprint which is a predictor of who might be at risk of developing this multi organ dysfunction syndrome?

Jo - Exactly. We’re looking to see what genes in our immune cells are activated, and what genes are maybe downregulated or suppressed so we think if we can find out what those initial key actors are in the first minutes or hours after injury; we might be able to figure out what is driving this huge response that we see later on down the line. And that’s not only useful for predicting organ dysfunction but it also opens up a huge avenue for discovery research to see are any therapeutics that we might be able to develop that can maybe modify that response.

Chris - How far have you got? Have you got some fingerprint changes now that are good predictors of people who might be at risk?

Jo - Yeah. We found that in the first window of injury, so that hyperacute phase, there are very specific immune changes that occur in that time frame which by 24 hours are no longer visible. We found a couple of key areas which might be important for subsequent development of therapeutics. One is the role of blood immune cells, things like natural killer cells which are a type of white blood cell. Neutrophils are also implicated in this response. So these are two cells types that we can start to work with to see if there’s anything we can develop to alter their response. But also with certain cellular pathways, these cell death pathways, were also featured very prominently and if we can find a drug or a therapeutic that can enhance cell survival, then we may be able to protect against organ dysfunction.

Chris - Do you think these people who you see who are at risk, is that something that they’re born with as in that’s part of their genetic repertoire? Or is it that the pre-existing situation perhaps they’d had a viral infection or they had something else wrong with their health that put them into this vulnerable state?

Jo - We don’t fully know the answer to that. We don’t know if it’s because of a patient's individual genetic makeup, or something that might have affected their genes as they were growing up, or up until the point that they had the injury, or whether it’s something to do with the injury itself specifically. These are still big questions that we need to answer in order to fully understand why some patients develop multiple organ dysfunction syndrome.

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