Variations in DNA methylation and allograft rejection

Abstract

DNA methylation is involved in gene transcription and as such important for cellular function. Here, the literature on DNA methylation in relation to acute rejection is summarized with a focus on the potential clinical utility of DNA methylation for monitoring transplant rejection. The tight transcriptional control of DNA methylation in immune cell function, e.g. demethylation in regulatory T-cell-specific genes for stable immunosuppressive capacities, suggests an important role for DNA methylation variations in the antidonor-directed immune response. Until today, differentially methylated DNA in immune cells, however, has not been described at the moment of allograft rejection. The ability to locus-specific modify DNA methylation could facilitate the generation of stable cells for cellular therapy purposes. The unique cell-specific characteristics of DNA methylation provide the opportunity to identify its cellular origin. Examining methylation of cell-free DNA in blood or urine may serve as a 'liquid biopsy' enabling minimally invasive detection of allograft rejection. Actual research publications on DNA methylation in relation to allograft rejection are scarce, which makes it challenging to determine its potential clinical value. Extensive research is needed to investigate the value of DNA methylation in early recognition, diagnosis, and/or successful treatment of allograft rejection.