Predictive Measures for Organ Transplant Rejections

Predictive Measures for Organ Transplant Rejections


While organ transplant operations have been increasingly successful over the past few years, the ultimate concern is whether the transplants will be successful in the long term. Unfortunately often, organ transplants get rejected, as the body’s immune system may suddenly attack the donor organ and cause it to fail. In heart transplants, the rate of organ rejection and patient mortality are the highest, even though the transplants are monitored by regular biopsies. Specifically, some 40% of heart recipients experience some type of severe rejection within one year of their transplant. It is clearly important to develop methods to detect the possible transplant rejection sooner, especially for organs like the heart. The solution might come from developing predictive measures for other types of organ transplants.

In heart transplants, the rate of organ rejection and patient mortality are the highest, even though the transplants are monitored by regular biopsies.

For example, patients with Type 1 diabetes sometimes undergo islet transplantation, which is the replacement of clusters of islet cells in the pancreas that control the blood sugar levels. High blood glucose levels are often indicators of tissue rejection; yet, this is only observed when rejection is imminent and at an advanced stage. Since almost 15% of islet transplant patients experience acute rejection, there clearly is a necessity for a better and earlier way to detect if an organ transplant might possibly be rejected, so that doctors can interfere before cell damage spreads dangerously and enhance patient survival rate. Recent studies have developed biomarkers to detect the possibility of islet transplant rejection, which shows promise in lowering the rate of acute rejection, and might plausibly be applicable to other organ transplants, such as the heart.

Here we present one such study. Specifically, researchers at University of Pennsylvania published a study in late March in which they used exosomes to determine whether islet cells might be rejected by the body. Exosomes are small vesicles, or bodies, outside of the cell that are released by various tissues into the bloodstream or other bodily fluids. Because these exosomes represent their tissue of origin biologically, quantifying and characterizing their presence within the bloodstream could serve as a biomarker for the new islet cells.

First, by transplanting islets from the human pancreas into diabetic mice, the researchers confirmed that exosomes released by islet cells express a certain protein on their surface, the HLA antigen. They then showed that a drastic decrease in the number of HLA-carrying exosomes in the bloodstream is almost always observed prior to an increase in blood sugar levels in the mice, which indicates a high likelihood of rejection. Besides the change in the number of exosomes detected in the bloodstream, an analysis of specific RNA and protein compositions of exosomes revealed numerical differences between normal exosomes and possible rejections.

To test their claim from their mouse models, the researchers attempted to detect islet-related exosomes in a clinical setting. In all the patients tested, exosomes from the donor islets could not be detected prior to transplant, as expected, while after the transplant, exosome levels became quantifiable. Notably, in one out of the five patients tested, a decrease in the number of cell exosomes was observed six months before the blood glucose levels rose, which thereafter led to rejection. The other four patients that did not show a drastic change in exosome level did not experience rejection, even after 5 years of follow-up. The researchers also managed to quantify and characterize exosomes from urine, showing the plausibility of utilizing this method in renal (kidney) transplantation, alongside pancreatic islet transplantation.

Indeed, the application of exosome detection as a biomarker for islet and renal transplants provides a solid foundation on which organ rejection can be predicted. Because the specific RNA and protein compositions of exosomes can also be analyzed, the exosome tool might have many future applications in other organ transplant models, such as heart or lung transplants, and even in other fields, such as stem cells and cancer. Overall, exosomes have been proposed to be a powerful predictive tool in the clinical realm of islet transplantation, which, with more research and trials, can be applied in predicting whether a patient will likely reject their organ many months before current standard techniques could.



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