Sepsis requires a personalized approach A better understanding of the immune system may provide starting points for therapy

In order to improve sepsis treatment, a better understanding of the patients' immune system is essential. To achieve this, researchers need to make greater use of artificial intelligence and omics techniques that can provide a more complete picture of the immune system. This is argued by researchers from Radboud university medical center, among others, in a review article published in The Lancet Respiratory Medicine. 

Twenty percent of all deaths in the world are related to sepsis, and in the Intensive Care unit, sepsis remains the leading cause of mortality. Sepsis is characterized by a combination of three factors: an infection, organ dysfunction - for instance kidney or lung injury - and a dysregulated immune response. Septic patients may become so ill that they require treatment in the Intensive Care unit, where approximately one out of three dies.  

We still lack specific therapies for sepsis, says researcher Matthijs Kox. 'We have antibiotics to tackle the infection, but next to that, there are only supportive therapies. Examples of these are mechanical ventilation in case of lung injury, or dialysis when patients develop kidney dysfunction. But so far, there is no specific therapy that has been proven to be effective against sepsis.'  

In their research, Kox and his colleagues focus on the immune system. This is important, according to Kox, because we still understand too little about the dysregulated immune response. ‘Whereas infection and organ dysfunction are fairly easy to diagnose, this is not so for a patient’s immune status. That largely remains a black box.' 

Hyperinflammation or paralysis 

With sepsis, two things can happen to the immune system: it can work too hard, causing a violent overreaction resulting in organ failure. Conversely, the immune system can also become paralyzed and cease to function. In that case, the infection is not cleared, and secondary infections can also develop. These are for example caused by fungi that do not cause problems in healthy people but are often difficult to treat. 

How can we better gauge the immune status? Within the European collaboration network EGIS, Kox and colleagues try to answer this question. In a recent publication in The Lancet Respiratory Medicine, they discuss the value of different biomarkers that can be measured in the blood and call for more research using modern omics techniques. With the help of artificial intelligence, a broad picture of the immune system can thereby be obtained. 

Many forms 

The authors of the article argue that for too long, sepsis has been considered a homogeneous state, in which every patient is treated in the same way. Kox: 'Fortunately, that idea is now outdated. Sepsis has so many forms. You can get it from pneumonia, but also from a bladder infection or a simple wound on your foot. And the extent and nature of immune dysregulation also varies between persons.' He makes the comparison with cancer: 'Oncologists do not treat all tumors in the same way. Bladder cancer is treated differently than breast cancer. And within those types of cancer, there is still a lot of variation. That is why the oncologists first determine the characteristics of the tumor and tailor the therapy based on those characteristics.' 

This is also the direction that sepsis treatment should take, according to Kox. He aims to better recognize a patient’s immune status: does he or she suffer from hyperinflammation or paralysis, and why? 'If we can determine this quickly in the acute Intensive Care setting, doctors can personalize their treatments. We have the therapies, but just do not know yet who should receive which drug and when.'

About this publication

This review appeared in The Lancet Respiratory Medicine: Profiling the dysregulated immune response in sepsis – overcoming challenges and reaching towards precision medicine. Sara Cajander, Matthijs Kox, Brendon Scicluna, Markus Weigand, Raquel Almansa Mora, Stefanie Flohé, […] Tomasz Skirecki, Marcin Osuchowski, Ignacio Rubio, Jesus Bermejo-Martin, Joerg Schefold, Fabienne Venet. 

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