221 Biomarkers of islet graft injury
Monday November 16, 2015 from 08:00 to 09:00
Plenary Room 1

Bashoo Naziruddin, United States


Transplant Services

Baylor SImmons Transplant Institute


Biomarkers of islet graft injury

Bashoo Naziruddin1.

1Transplant Services, Baylor Simmons Transplant Institute, Dallas, TX, United States

Pancreatic islet transplantation is a promising treatment for patients with “brittle” type 1 diabetes or intractable chronic pancreatitis to restore or preserve pancreatic endocrine function. A significant mass of islets have been shown to be damaged during peritransplant period due to innate inflammatory response and further loss of islet graft occurs in the long term due to immune response or metabolic exhaustion. Identification of specific, sensitive and reproducible biomarkers of islets will lead to development of preventative and interventional treatment strategies to prevent islet graft damage.  Some of the criteria to consider when evaluating a biomarker are sensitivity, specificity, rapid detection, reproducibility, accuracy and inexpensive method. In clinical practice, islet graft function is monitored by metabolic function via blood glucose, insulin and c-peptide levels as well as islet imaging. However, these tests are influenced by physiological changes including beta cell stimulation. Biomarkers that are independent of metabolic stimuli will be of greater value to detect islet injury. Antibodies against islet autoantigens are useful but not reliable markers of islet injury due to their presence during pretransplant period. Several islet specific proteins such as GAD65, DCX, PPP1R1A, UCHL1 and HMGB1 are candidates for islet injury markers but suffer from difficulties in detection and accurate measurement. Unmethylated insulin DNA has been studied in type 1 diabetes patients has been documented as an excellent biomarker for beta cell death. Recent studies have demonstrated the value of microRNAs (miRNA), a class of noncoding RNA that are involved in regulation of gene expression and cellular function. MiRNAs are present in the extracellular fluids in stable and easily detectable forms.  A number of miRNAs specific for islets have been reported recently. A prominent miRNA that has been studied as an islet injury marker is miR375, which is highly conserved between mice and humans. Analysis of plasma samples from autologous and allogeneic islet transplant patients has documented the value of miR375 as biomarker to accurately measure islet injury. Further progress using islet specific biomarker will be to assess islet damage during organ recovery, isolation, culture and post-transplantation. 

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