Combined Analysis of GAD65, miR-375, and Unmethylated Insulin DNA Following Islet Transplantation in Patients With T1D
Autor: | Pieter Gillard, Frans Gorus, Zhidong Ling, Eric V. Balti, Sarah A. Tersey, Olivier Costa, Geert Stangé, Daniel Pipeleers, Bart Keymeulen, Sarah Roels, Raghavendra G. Mirmira, Dieter De Smet, Geert A. Martens |
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Přispěvatelé: | Faculty of Medicine and Pharmacy, Pathology/molecular and cellular medicine, Diabetes Pathology & Therapy, Clinical Biology, Medicine and Pharmacy academic/administration, Diabetes Clinic, Vriendenkring VUB |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Adult Graft Rejection medicine.medical_specialty medicine.medical_treatment Endocrinology Diabetes and Metabolism Clinical Biochemistry Islets of Langerhans Transplantation Biochemistry 03 medical and health sciences endocrinology 0302 clinical medicine In vivo Diabetes mellitus Internal medicine medicine Humans Insulin Postoperative Period Liquid biopsy Clinical Research Articles Biochemistry medical geography geography.geographical_feature_category business.industry Glutamate Decarboxylase Biochemistry (medical) Autoantibody DNA Methylation Middle Aged Islet medicine.disease Prognosis Transplantation MicroRNAs 030104 developmental biology Endocrinology Diabetes Mellitus Type 1 030220 oncology & carcinogenesis DNA methylation business Biomarkers Follow-Up Studies |
Zdroj: | The Journal of Clinical Endocrinology & Metabolism |
ISSN: | 0021-972X |
DOI: | 10.1210/jc.2017-02520 |
Popis: | AIM: Several biomarkers have been proposed to detect pancreatic β cell destruction in vivo but so far have not been compared for sensitivity and significance. METHODS: We used islet transplantation as a model to compare plasma concentrations of miR-375, 65-kDa subunit of glutamate decarboxylase (GAD65), and unmethylated insulin DNA, measured at subpicomolar sensitivity, and study their discharge kinetics, power for outcome prediction, and detection of graft loss during follow-up. RESULTS: At 60 minutes after transplantation, GAD65 and miR-375 consistently showed near-equimolar and correlated increases proportional to the number of implanted β cells. GAD65 and miR-375 showed comparable power to predict poor graft outcome at 2 months, with areas under the curve of 0.833 and 0.771, respectively (P = 0.53). Using receiver operating characteristic analysis, we defined likelihood ratios (LRs) for rationally selected result intervals. In GADA-negative recipients (n = 28), GAD65 12.2 pmol/L (LR = ∞) predicted good and poor outcomes, respectively. miR-375 could be used in all recipients irrespective of GAD65 autoantibody status (n = 46), with levels 7.6 pmol/L (LR = 9.53) as dual thresholds. The posttransplant surge of unmethylated insulin DNA was inconsistent and unrelated to outcome. Combined measurement of these three biomarkers was also tested as liquid biopsy for β cell death during 2-month follow-up; incidental surges of GAD65, miR-375, and (un)methylated insulin DNA, alone or combined, were confidently detected but could not be related to outcome. CONCLUSIONS: GAD65 and miR-375 performed equally well in quantifying early graft destruction and predicting graft outcome, outperforming unmethylated insulin DNA. |
Databáze: | OpenAIRE |
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