Digging into biomarkers of immunologic transplant rejection
William Aryitey |
“There is a critical need for time-sensitive, noninvasive biomarkers to monitor transplant organ rejection or injury,” says Prashanth Vallabhajosyula, assistant professor of surgery at the Hospital of the University of Pennsylvania. “In transplant patients, complications associated with transplant organ rejection/injury, and with the required immunosuppressive drugs, are the major causes of morbidity and mortality. Therefore, any biomarker platform that can accurately enable noninvasive monitoring of the transplanted organ would have a direct translational impact.” To that end, Vallabhajosyula and a team of researchers (also from the University of Pennsylvania) showed that blood-based transplant exosomes can be a noninvasive alternative to needle biopsy in islet and renal transplants (1).
The investigators transplanted human islets xenogeneically into mice and found that transplanted islets undergoing rejection quickly expressed a lower level of exosome signaling via miRNA. “I was expecting to see changes in transplant tissue-specific exosomes in a time-specific manner, but it surprised me to see the changes occur so early in the acute rejection process – when there was minimal T cell infiltration and no damage of the allograft,” says Vallabhajosyula. “We sincerely believe that our proposed exosome platform will enable development of a noninvasive biomarker for monitoring transplanted tissues – and that means earlier detection of rejection, minimized need for frequent tissue biopsy of the transplanted tissue, and titration of immunosuppression based on the status of the transplanted organ.”
But that’s not all; Vallabhajosyula suggests that transplant tissue exosomes could be manipulated in vitro and then reintroduced into the host... The first glimpse of a new therapy on the horizon?
- P Vallabhajosyula et al., “Tissue-specific exome biomarkers for noninvasively monitoring immunologic rejection of transplanted tissue”, The Journal of Clinical Investigation, 127, 1375–1391 (2017). PMID: 28319051.