RT info:eu-repo/semantics/article
T1 Beta cell death by cell-free DNA and outcome after clinical islet transplantation
A1 Gala Lopez, Boris L.
A1 Neiman, Daniel
A1 Kin, Tatsuya
A1 O’Gorman, Doug
A1 Pepper, Andrew R.
A1 Malcolm, Andrew J.
A1 Pianzin, Sheina
A1 Senior, Peter A.
A1 Campbell, Patricia
A1 Glaser, Benjamin
A1 Dor, Yuval
A1 Shemer, Ruth
A1 Shapiro, A.M. James
AB Background: Optimizing engraftment and early survival after clinical islet transplantation is critical to long-term function, but there are no reliable, quantifiable measures to assess beta cell death. Circulating cell free DNA (cfDNA) derived from beta cells has been identified as a novel biomarker to detect cell loss, and was recently validated in new-onset type 1 diabetes and in islet transplant patients. Methods: Herein we report beta cell cfDNA measurements after allotransplantation in 37 subjects and the correlation with clinical outcomes. Results: A distinctive peak of cfDNA was observed 1hr after transplantation in 31/37 (83.8%) of subjects. The presence and magnitude of this signal did not correlate with transplant outcome. The 1hr signal represents dead beta cells carried over into the recipient after islet isolation and culture, combined with acute cell death post infusion. Beta cell cfDNA was also detected 24hrs post-transplant (8/37 subjects, 21.6%). This signal was associated with higher 1-month insulin requirements (p=0.04), lower 1-month stimulated C-peptide levels (p=0.01) and overall worse 3-month engraftment, by insulin independence (ROC:AUC=0.70, p=0.03) and Beta 2 score (ROC:AUC=0.77, p=0.006). Conclusions: cfDNA-based estimation of beta cell death 24hrs after islet allotransplantation correlates with clinical outcome and could predict early engraftment.
PB Wolters Kluger
SN 0041-1337
YR 2018
FD 2018
LK http://uvadoc.uva.es/handle/10324/36577
UL http://uvadoc.uva.es/handle/10324/36577
LA spa
NO Transplantation, June 2018, 102. 978-985
DS UVaDOC
RD 14-oct-2024