2013 - CTS 2013 Congress

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Oral Communications 3

8.3 - Circulating miR-375 levels after islet transplantation in humans: a biomarker of ongoing beta cell injury

Presenter: Lorenzo, Piemonti, Milan, Italy
Authors: Lorenzo Piemonti1,2, Miguel Correa-Tapia 1,2, Vito Lampasona1,2, Jorge Ferrer1,2

Circulating miR-375 levels after islet transplantation in humans: a biomarker of ongoing beta cell injury

Lorenzo Piemonti1,2, Miguel Correa-Tapia 1,2, Vito Lampasona1,2, Jorge Ferrer1,2

1Diabetes Research Institute (OSR-DRI), San Raffaele Scientific Institute, Milan, Italy; 2Genomic Programming of Beta-cells Laboratory, Institut d'Investigacions August Pi i Sunyer (IDIBAPS); CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcellona, Spain


Background.Circulating level of the pancreatic islet enriched miR-375  was recently described as a biomarker of  beta cell death1. We tested if circulating levels of miR-375 reflect beta cell destruction in patients with type 1 diabetes  who received human pancreatic islets.
Methods/Materials.A total of 22 human islet infusion were studied under different immunosuppression regimen: alphaCD25/Rapa/FK506 (n=6), ATG/MMF/FK506 (n=13) and none (auto trasplantation; n=3). MiR-375 circulating levels were evaluated by quantitative PCR (TaqMan Assay and/or droplet digital PCR).
Results.Human pancreatic islet expressed high level of miR-375. After transplantation serum miR-375 increased up to 200-fold during the first 12 hours, and then dropped to moderately elevated levels after 24 hours. This change was present both in allogenic and autologous islet transplantation. Circulating miR-375 levels were again increased at 96 hours post islet-infusion. This second peak  was  preceded by the rise of C-reactive protein  and cross-linked fibrin degradation products, and it was followed by the rise of cell damage markers (AST, ALT and LDH). We compared miR-375 levels in patients with and without CXCR1/2 inhibitor therapy, a treatment that preserves <beta> cell mass by dampening inflammatory damage (Citro, A. et al J. Clin. Invest. 2012;122:3647). All patients showed similarly increased circulating miR-375 levels during the 24 hr period that followed the infusion. However, the elevations of miR-375 levels that were observed at 48 and 96 hours post-islet infusion in control patients were not observed  in patients treated with CXCR1/2inihibitors (p=0.048 and 0.024, respectively). Concordantly, CXCR1/2 inhibitor therapy preserved increased beta cell function during the time.

Conclusion.The results suggest that circulating miR-375 levels is a useful non-invasive indicator of ongoing beta cell injury after islet transplantation.

1. Erener,  S. et al.  Endocrinology  2013; 154:603

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