Neutrophil-derived miR-223 as local biomarker of bacterial peritonitis
Amy C Brook1, Robert H Jenkins1,2, Aled Clayton3
1Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
Abstract:
Infection remains a major cause of morbidity, mortality and technique failure in patients with end stage kidney failure who receive peritoneal dialysis (PD). Recent research suggests that the early inflammatory response at the site of infection carries diagnostically relevant information, suggesting that organ and pathogen-specific "immune fingerprints" may guide targeted treatment decisions and allow patient stratification and risk prediction at the point of care. Here, we recorded microRNA profiles in the PD effluent of patients presenting with symptoms of acute peritonitis and show that elevated peritoneal miR-223 and reduced miR-31 levels were useful predictors of bacterial infection. Cell culture experiments indicated that miR-223 was predominantly produced by infiltrating immune cells (neutrophils, monocytes), while miR-31 was mainly derived from the local tissue (mesothelial cells, fibroblasts). miR-223 was found to be functionally stabilised in PD effluent from peritonitis patients, with a proportion likely to be incorporated into neutrophil-derived exosomes. Our study demonstrates that microRNAs are useful biomarkers of bacterial infection in PD-related peritonitis and have the potential to contribute to disease-specific immune fingerprints. Exosome-encapsulated microRNAs may have a functional role in intercellular communication between immune cells responding to the infection and the local tissue, to help clear the infection, resolve the inflammation and restore homeostasis.
Insights
New biomarkers, microRNAs (miRNAs), in peritoneal dialysis (PD) effluent can predict bacterial infection in patients with end-stage kidney failure. Elevated miR-223 and reduced miR-31 levels offer diagnostic insights for peritonitis, aiding targeted treatment.
Area of Science:
- Biochemistry
- Immunology
- Nephrology
Background:
- Infection is a primary complication in patients undergoing peritoneal dialysis (PD), leading to significant morbidity and mortality.
- Early detection and targeted treatment of PD-related infections, such as peritonitis, are crucial for patient outcomes.
- The concept of "immune fingerprints" using molecular profiles for diagnosis and risk stratification is emerging.
Purpose of the Study:
- To investigate microRNA (miRNA) profiles in PD effluent as potential biomarkers for bacterial peritonitis.
- To determine if specific miRNAs can predict bacterial infection and aid in patient management.
- To explore the cellular origins and potential functions of identified miRNAs in the context of peritonitis.
Main Methods:
- Analysis of miRNA profiles in peritoneal dialysis effluent from patients with suspected acute peritonitis.
- Cell culture experiments to identify the cellular sources of key miRNAs (miR-223 and miR-31).
- Investigation of miRNA stability and potential packaging into exosomes in PD effluent.
Main Results:
- Elevated levels of peritoneal miR-223 and reduced levels of miR-31 were identified as predictors of bacterial infection.
- miR-223 was primarily produced by immune cells (neutrophils, monocytes), while miR-31 originated from local peritoneal tissue.
- miR-223 demonstrated functional stability in PD effluent and was found in neutrophil-derived exosomes.
Conclusions:
- MicroRNAs are valuable biomarkers for diagnosing bacterial infection in PD-related peritonitis.
- These miRNA profiles can contribute to developing disease-specific "immune fingerprints" for personalized medicine.
- Exosome-encapsulated miRNAs may play a role in intercellular communication during infection response and resolution.
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