Sepsis is a life-threatening infection and affects people in a multitude of ways depending on genetic makeup. A team of researchers has uncovered how genes could play a role in developing personalised sepsis treatment to treat this infection more efficiently.
A team from the Wellcome Sanger Institute and the University of Oxford built on their previous work that identified different subgroups of patients with sepsis to gain a further understanding of why sepsis response varies between patients.
The new study details how genetics could be used to develop personalised sepsis treatments and uncover the variability in infection response, different regulators and cell types involved in the different immune responses in the patient subgroups.
Using the right sepsis treatment is the difference between life and death
Sepsis causes an estimated 11 million deaths worldwide per year, with one death every three seconds. When the body has an extreme response to an infection, it begins injuring its tissues and organs. Depending on this immune response, treatment varies. A more detailed understanding of the infections molecular level could identify patients requiring different treatments than standard, help design rapid tests, organise clinical trials, and develop targeted sepsis treatments.
In previous research, the team identified how the expression of a small set of genes allowed them to categorise who was most at risk from poorer outcomes from sepsis and COVID-19. Building on this, the new study investigated the impact of genetic variants that regulate gene expression, known as expression quantitative trait locus, or eQTLs. The provides insight into individual genetic makeup and how it may influence immune response, allowing the researchers to classify who would benefit from personalised sepsis treatment.
Personalised medicine could be key to tackling sepsis
The team used data from the UK Genomic Advances in Sepsis (GAinS) study that contained 1,400 patients with sepsis due to community-acquired pneumonia and faecal peritonitis3 from intensive care units across the UK.
They found that genetic variation in groups of patients is associated with differences in immune response during sepsis. They then used this to identify key genetic regulators in each group, helping to describe what biological networks, cells, and mechanisms are involved in each response.
Understanding the regulatory networks underlying the different patient responses provides additional information for developing sepsis treatments that work with the immune system and moves the researchers closer to developing personalised medicine.
The next steps are to further investigate the immune response to find targeted sepsis treatment for each immune response or different stages of the immune response.
Dr Katie Burnham, first author from the Wellcome Sanger Institute, said: “Our study is the next step towards being able to treat sepsis based on someone’s genetics and their particular immune response, instead of their symptoms, which can vary greatly from person to person. Our research found two groups of people, with opposite immune responses, and identified the genetic regulators involved. Being able to molecularly categorise patients with sepsis allows clinicians to correctly identify who could benefit from the available treatments and gives new direction to those developing targeted therapies.”
Dr Julian Knight, co-senior author from the University of Oxford, said: “Understanding who is at greater risk from sepsis and how they respond to the disease is a huge task. Research such as this, which dives deeper into the molecular basis of the disease, aids in the ongoing development of tests that could identify different subtypes of sepsis and allow medical professionals to treat this straight away. Our research can be directly translated into the clinic and we hope that it allows us to start to develop an efficient, targeted approach to treating this life-threatening disease.”
