2024-03-28T12:50:25Zhttp://uvadoc.uva.es/oai/requestoai:uvadoc.uva.es:10324/365772021-06-24T07:27:45Zcom_10324_22821com_10324_954com_10324_894col_10324_22822
Gala Lopez, Boris L.
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500
Neiman, Daniel
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500
Kin, Tatsuya
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500
O’Gorman, Doug
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500
Pepper, Andrew R.
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500
Malcolm, Andrew J.
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500
Pianzin, Sheina
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500
Senior, Peter A.
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500
Campbell, Patricia
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500
Glaser, Benjamin
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500
Dor, Yuval
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500
Shemer, Ruth
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Shapiro, A.M. James
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2019-07-02T13:20:16Z
2019-07-02T13:20:16Z
2018
Transplantation, June 2018, 102. 978-985
0041-1337
http://uvadoc.uva.es/handle/10324/36577
10.1097/TP.0000000000002083
978
6
985
Transplantation
102
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.
B.G.-L. is supported through the Alberta Innovates :Health Solutions (AIHS) Clinician Fellowship and through the CNTRP. A.P. is supported through AIHS Postgraduate Fellowship and CNTRP. A.M.J.S. is supported through AIHS, and holds a Canada Research Chair in Transplantation Surgery and Regenerative Medicine funded through the Government of Canada. A.M.J.S. is also funded by AIHS Collaborative Research and Innovation Opportunity Team Award and the Diabetes Research Institute Foundation of Canada (DRIFCan). Supported by grants from the Juvenile Diabetes Research Foundation (JDRF) (3-SRA-2014-38-Q-R, to Y.D. and A.M.J.S.), National Institute of Health (NIH) (HIRN grant UC4 DK104216, to Y.D.), DON foundation (Stichting Diabetes Onderzoek Nederland) (to Y.D), the European Union (ELASTISLET project, to Y.D.) and the Kahn foundation (to Y.D., R.S., and B.G.). Supported in part by a grant from The United States Agency for International Development (USAID) American Schools and Hospitals Abroad Program for the upgrading of the Hebrew University sequencing core facility
application/pdf
spa
Wolters Kluger
info:eu-repo/semantics/openAccess
Beta cell death by cell-free DNA and outcome after clinical islet transplantation
info:eu-repo/semantics/article
info:eu-repo/semantics/submittedVersion
https://insights.ovid.com/crossref?an=00007890-201806000-00025
SI
THUMBNAIL
Beta-Cell-Death-Transplantation-2017.pdf.jpg
Beta-Cell-Death-Transplantation-2017.pdf.jpg
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https://uvadoc.uva.es/bitstream/10324/36577/4/Beta-Cell-Death-Transplantation-2017.pdf.jpg
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ORIGINAL
Beta-Cell-Death-Transplantation-2017.pdf
Beta-Cell-Death-Transplantation-2017.pdf
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452780
https://uvadoc.uva.es/bitstream/10324/36577/3/Beta-Cell-Death-Transplantation-2017.pdf
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LICENSE
license.txt
license.txt
text/plain
3926
https://uvadoc.uva.es/bitstream/10324/36577/2/license.txt
017313583e37a1e4d1253e1ef6c66c6c
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10324/36577
oai:uvadoc.uva.es:10324/36577
2021-06-24 09:27:45.21
UVaDOC
repositorio@uva.es
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