Beta Cell Death by Cell-free DNA and Outcome After Clinical Islet Transplantation. Issue 6 (June 2018)

• Record Type: Journal Article
• Authors: Gala-Lopez, Boris L.; Neiman, Daniel; Kin, Tatsuya; O'Gorman, Doug; Pepper, Andrew R.; Malcolm, Andrew J.; Pianzin, Sheina; Senior, Peter A.; Campbell, Patricia; Glaser, Benjamin; Dor, Yuval; Shemer, Ruth; Shapiro, A.M. James
• Is Part Of: Transplantation. Volume 102:Issue 6(2018)
• Publication Date: 2018-06
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000002083
• Languages: English
• ISSNs: 0041-1337

Abstract

Abstract : 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 1 hour after transplantation in 31 (83.8%) of 37 subjects. The presence and magnitude of this signal did not correlate with transplant outcome. The 1-hour 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 24 hours posttransplant (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 (receiver operating characteristic-area under the curve = 0.70, P = 0.03) and beta 2 score (receiver operating characteristic-area under the curve = 0.77, P = 0.006). Conclusions: cfDNA-based estimation of beta cell death 24 hours after islet allotransplantation correlates with clinical outcome and could predict early engraftment. Abstract : Death and injury can lead to release of cell-free DNA in transplantation. The level of cell-free DNA released at 1 hour after islet transplantation reflects beta cell death from the processing, culture, and implantation of islets and does not correlate with outcomes, but the level at 24 hours after transplantation does. Supplemental digital content is available in the text.