microRNA-375 Provides an Objective Measure of Pancreas Quality in Organ Donors

I. Shapey¹, A. Summers¹, J. O'Sullivan¹, P. Yiannoullou¹, J. Casey², S. Forbes², M. Rosenthal³, P. Johnson⁴, P. Choudhary¹, J. Bushnell⁵, J. Shaw⁶, N. Hanley¹, T. Augustine¹, M. Rutter¹, D. van Dellen¹

¹University of Manchester, Manchester, United Kingdom, ²University of Edinburgh, Edinburgh, United Kingdom, ³Royal Free Hospital, London, United Kingdom, ⁴University of Oxford, Oxford, United Kingdom, ⁵Southmead Hospital, Bristol, United Kingdom, ⁶University of Newcastle, Newcastle, United Kingdom

Meeting: 2019 American Transplant Congress

Abstract number: 360

Keywords: Gene expression, Insulin, Islets, Pancreas

Session Information

Session Name: Concurrent Session: Biomarkers, Immune Monitoring and Outcomes III

Session Type: Concurrent Session

Date: Monday, June 3, 2019

Session Time: 4:30pm-6:00pm

Presentation Time: 4:54pm-5:06pm

Location: Room 306

*Purpose: Donor pancreatic beta cells are at high risk from apoptosis. Objective methods for assessing the quality of donor pancreases for transplantation are limited. We hypothesized that microRNA (miR)-375, a marker of beta cell death in islet transplant recipients, could be used as a circulating cell-free biomarker of beta cell death in organ donors.

*Methods: Plasma samples from 100 donor after brain death pancreas donors were collected by the Quality in Organ Donation Biobank: a) at the time of consent; and b) at aortic cross clamp during organ retrieval. We used linear regression to relate miR-375 levels to donor glucose, c-peptide and levels of biomarkers of beta-cell apoptosis (all n=100), and to islet viability in 17 donor pancreases from which islets were isolated for transplantation.

*Results: Medan (IQR) donor age was 35 (25-49) years and BMI 24 (22-26) kg/m². Circulating cell-free miR-375 levels were related to lower islet viability (figure 1) and higher peak donor blood glucose (linear regression β [se]: -4.01 [0.16], p=0.047), but not C-peptide (-0.87 [2.6×10^-7], p=0.435). MiR-375 was strongly related to miR regulators of beta-cell death (miRs: 34-a: 0.73 [0.12]; 200b: 1.42 [0.21] and 200c: 0.89 [0.21]; all p<0.001). Markers of apoptosis, measured at the time of consent, were positively related to miR-375 during the donation period (Granzyme B, 7.65 [2.22], p=0.001; TNF-related apoptosis-inducing ligand, 2.96 [1.24], p=0.019). Persistently high levels of IL-6 throughout the donation period were associated with greater expression of miR-375 (1.46 [0.63], p=0.023). MiR-375 levels were independent of any clinical variables, including donor age and BMI.

*Conclusions: Circulating cell-free microRNA-375 could have clinical utility in the objective assessment of the quality of pancreases for transplantation. It might also be useful outcome measure in intervention studies aiming to reduce beta-cell apoptosis in donor pancreases. Research is required to determine whether such interventions could improve transplant outcomes.

To cite this abstract in AMA style:

Shapey I, Summers A, O'Sullivan J, Yiannoullou P, Casey J, Forbes S, Rosenthal M, Johnson P, Choudhary P, Bushnell J, Shaw J, Hanley N, Augustine T, Rutter M, Dellen Dvan. microRNA-375 Provides an Objective Measure of Pancreas Quality in Organ Donors [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/microrna-375-provides-an-objective-measure-of-pancreas-quality-in-organ-donors/. Accessed November 22, 2024.

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