Combined Analysis of GAD65, miR-375, and Unmethylated Insulin DNA Following Islet Transplantation in Patients With T1D

• DOI: 10.1210/jc.2017-02520
• Publication Date: 2018-09-07T14:03:30Z
• Authors: Sarah Roels; Olivier R Costa; Sarah A Tersey; Geert Stangé; Dieter De Smet; Eric V Balti; Pieter Gillard; Bart Keymeulen; Zhidong Ling; Daniel G Pipeleers; Frans K Gorus; Raghavendra G Mir...; Geert A Martens
• Keywords: Adult; Graft Rejection; 0301 basic medicine; Biochimie; Islets of Langerhans Transplantation; 03 medical and health sciences; Métabolisme; Diabetes Mellitus; Humans; Insulin; Postoperative Period; Diabétologie; Médecine clinique [chimie clinique]; DNA methylation; Glutamate Decarboxylase; DNA Methylation; Middle Aged; Prognosis; Endocrinologie; MicroRNAs; Diabetes Mellitus, Type 1; Graft rejection; Biomarkers; Type 1; Follow-Up Studies

Several biomarkers have been proposed to detect pancreatic β cell destruction in vivo but so far not compared for sensitivity and significance.We used islet transplantation as a model compare plasma concentrations of miR-375, 65-kDa subunit glutamate decarboxylase (GAD65), unmethylated insulin DNA, measured at subpicomolar sensitivity, study their discharge kinetics, power outcome prediction, detection graft loss during follow-up.At 60 minutes after transplantation, GAD65 miR-375 consistently showed near-equimolar correlated increases proportional the number implanted cells. comparable predict poor 2 months, with areas under curve 0.833 0.771, respectively (P = 0.53). Using receiver operating characteristic analysis, we defined likelihood ratios (LRs) rationally selected result intervals. In GADA-negative recipients (n 28), <4.5 pmol/L (LR 0.15) >12.2 ∞) predicted good outcomes, respectively. could be all irrespective autoantibody status 46), levels <1.4 0.14) or >7.6 9.53) dual thresholds. The posttransplant surge DNA was inconsistent unrelated outcome. Combined measurement these three also tested liquid biopsy death 2-month follow-up; incidental surges GAD65, (un)methylated alone combined, were confidently detected related outcome.GAD65 performed equally well quantifying early predicting outcome, outperforming DNA.