How an individual's genetics influences their immune systems' response to sepsis has been investigated by a team of UK researchers.

Researchers at the Wellcome Sanger Institute, the University of Oxford, and collaborators studied the underlying molecular mechanisms involved in sepsis by building on previous work in which they identified different subgroups of sepsis patients. The new study, published in Cell Genomics, investigated the underlying immune response pathways to better understand why different patients react differently to sepsis.

Dr Emma Davenport, co-senior author from the Wellcome Sanger Institute said: 'Sepsis is a complicated and devastating disease that impacts millions of people around the world each year. Understanding the molecular processes that happen during sepsis, and how genetics plays a role in this, can help give answers to long-standing questions, improve patient outcomes, and allow for the development of effective clinical trials that lead to new targeted treatments as quickly as possible.'

During sepsis, the body's response to an infection results in damage to its own tissues and organs, which can cause different downstream immune responses for different people. Depending on this resulting immune response, the treatment for sepsis can vary, but it is currently difficult to identify the type of immune response that is happening by symptoms alone. As sepsis progresses quickly, the wrong treatment means that the patients lose valuable time.

This new study is based on previous work in which the researchers identified a small set of genes that could predict which sepsis patients were at a higher risk for a poorer outcome. Using data from the UK Genomic Advances in Sepsis study, the researchers looked at the impact genetic variants have on the regulation of these genes.

The researchers found that the differences in genetics were associated with differences in how the patients' immune systems responded during sepsis. They were also able to better define the biological networks, cells and mechanisms that are involved in the varied responses.

Dr Katie Burnham, first author of the study 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.'

Related research at the University of Oxford is trying to develop a rapid test that could identify the different subtypes of sepsis, but there is still a way to go before this could be used in a clinical setting.