Free-Circulating Nucleic Acids as Biomarkers in Patients After Solid Organ Transplantation

A number types of extracellular DNA (eg, cell-free, cfDNA) circulate in human blood, including mitochondrial, transcriptome, and regulatory DNA, usually at low concentrations. Larger amounts of cfDNA appear in any inflammatory condition, including organ damage due to a variety of reasons. The role of cfDNA in solid organ transplantation is discussed in this review as a valuable additional tool in the standard of care of transplant patients. Post-transplant monitoring requires the use of high-quality biomarkers for early detection of graft damage or rejection to be able to apply early therapeutic intervention. CfDNA complements the traditional monitoring strategies, being a risk stratification tool and an important prognostic marker. However, improving the sensitivity and specificity of cfDNA detection is necessary to facilitate personalized patient management, warranting further research in terms of measurement, test standardization, and storage, processing, and shipping. A diagnostic test (Allosure, CareDx, Inc., Brisbane, CA) for kidney, heart and lung transplant patients is now commercially available, and validation for other organs (eg, liver) is pending. To date, donor-derived cfDNA in combination with other biomarkers appears to be a promising tool in graft rejection as it is minimally invasive, time-sensitive, and cost-effective. However, improvement of sensitivity and specificity is required to facilitate personalized patient management. Whether it could be an alternate to graft biopsy remains unclear.

Automated summary

This review discusses various types of extracellular DNA (such as cell-free DNA) that circulate in human blood, particularly in inflammatory conditions and organ damage. Cell-free DNA (cfDNA) is considered a valuable additional tool in the post-transplant monitoring of transplant patients, complementing traditional strategies and serving as a risk stratification and prognostic marker. Improved sensitivity and specificity in cfDNA detection are necessary for personalized patient management, and further research is needed in terms of measurement, standardization, and processing.