Cell-free DNA (cfDNA) - fragments of genetic material released into the bloodstream - is increasingly used as a non-invasive biomarker in areas such as cancer detection, prenatal screening, and organ transplant monitoring. However, its role in acute conditions like infection is not yet fully understood.
Sepsis is a life-threatening condition caused by the body’s response to infection, leading to widespread inflammation, tissue damage, and organ failure. Despite its severity and prevalence, diagnosing and monitoring sepsis and organ failure remains challenging. Previous studies have shown that cfDNA levels rise during sepsis, and have suggested this increase reflects disease severity and is a by-product of tissue damage.
Now, researchers from the Song lab at Ludwig Oxford and collaborators from the Centre for Human Genetics, have shown that cfDNA could also offer vital insights into the body’s response to sepsis. The study, published in Cell Genomics, reveals that cfDNA levels rise sharply during acute sepsis - not due to excessive cell death, but because of impaired clearance by the liver.
By analysing the size, sequence and tissue-specific methylation patterns of cfDNA fragments in patients with sepsis, the team found that cfDNA retains gene activity footprints, offering insights into which tissues are affected during infection. Notably, DNA fragments from Kupffer cells (specialised liver macrophages) and liver parenchyma were elevated in patients with liver dysfunction, pointing to a failure in hepatic clearance mechanisms. This approach could complement existing liver function tests by offering a more dynamic, tissue-specific view of organ health through a simple blood sample.
The study also detected pathogen-derived DNA in the bloodstream, specifically from E. coli, Staphylococcus and Enterococcus, suggesting that cfDNA could also serve as a non-invasive biomarker for infection. This could be of particular use in cases where the infecting pathogen doesn’t grow in laboratory conditions, or takes several days to culture.
These findings open up new possibilities for using cfDNA to monitor liver function, organ failure, and immune cell turnover during disease, and guide treatment decisions in critical care settings.