Researchers discover test for earlier detection of transplant rejection

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Dr. Prashanth Vallabhajosyula (Photo: University of Pennsylvania)

An Indian-American researcher at University of Pennsylvania, and his team have discovered a test to more quickly detect if a body is rejecting a transplant.

Faster than existing methods, the new test would be a boon for patients and the medical community because, of the approximately 30,000 organ transplants that take place in the U.S. annually, between 20 and 50 percent fail within five years.

A better biomarker would allow doctors to reverse rejection episodes in many of these cases using immunosuppressive drugs. Plus, if further studies confirm the validity of these tests, doctors could keep transplant recipients healthier and their transplants working longer, the researchers believe.

Dr. Prashanth Vallabhajosyula, assistant professor of Cardiovascular Surgery in the Perelman School of Medicine at UPenn, and Dr. Ali Naji, the J. William White Professor of Surgery, lead authors of the study, have discovered a method that appears to provide earlier warning of organ transplant rejection compared to standard methods, and requires only a blood test rather than a more invasive and painful needle biopsy. This new method is detailed in a study published March 20, in the online edition of the Journal of Clinical Investigation.

“There is a critical need for a biomarker that will work across the entire field of transplantation and will allow us to detect rejection and intervene much sooner than we are currently able to,” Vallabhajosyula, the lead author said. “We think our proposed biomarker platform could fulfill that need.”

The new method involves tiny, capsule-like structures known as exosomes, which normally are secreted from most types of cell.

Using a standard laboratory model in which human pancreatic islet cells—key producers of insulin—are transplanted into mice,  researchers showed that they could indeed detect and quantify the exosomes from the donated human cells in the blood of the mice. Moreover, when the researchers induced an immune rejection of the transplants in the mice, the detected levels of transplanted-islet exosomes dropped sharply and almost immediately.

“The levels of those exosomes in the bloodstream changed dramatically, well before we saw changes in other current clinical markers such as fasting glucose levels,” Vallabhajosyula said. Researchers suspect that taking these changes into account could increase the reliability of the test for early detection of transplant rejection.

In further tests, specifically relating to kidney transplants, the team found that they could isolate and quantify donor-kidney exosomes not just in blood but also in urine, thus holding out the possibility that urine tests, even less invasive than blood tests, could also indicate rejection.

The researchers are now following up with further studies, including studies of their method with different types of transplantation.

Vallabhajosyula received his Bachelor of Science and Masters of Science in molecular biophysics and biochemistry, along with his Doctor of Medicine degrees from Yale University, New Haven, CT. He completed his residency in general surgery at Johns Hopkins Hospital, Baltimore, MD. During this period, he did a clinical fellowship in upper gastrointestinal surgery at Oxford-Radcliffe Hospitals, Oxford, United Kingdom.

He attended the Hospital of University of Pennsylvania for a fellowship in cardiothoracic surgery, and completed a sub-specialization year in aortic surgery, along with endovascular and minimally invasive techniques. His surgical interests are in aortic surgery, endovascular surgery and thoracic organ transplantation.

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