Circulating Donor-Derived Cell-Free DNA as a Noninvasive Biomarker for Allograft Rejection in Vascularized Composite Allotransplantation
Abstract
This project addresses the Fiscal Year 2016 Restorative Transplantation Research Focus Area of “Graft clinical monitoring - acute and chronic, as applied to VCA; Development of biomarker profiling methods for early reliable detection of graft rejection.” Immune rejection is the most common complication of restorative transplants such as face or hand transplants. In most cases, immune rejection is treatable if it is detected and treated timely. For this reason, restorative transplant surgeons follow up their patients closely and frequently take small samples of the transplant’s skin to look for rejection. Taking these samples can be uncomfortable for the patients and can cause a small amount of scarring. Another downside of looking for rejection in these small skin samples is that there are other skin conditions, such as allergies or a sunburn, that can look very similar to rejection and prompt unnecessary treatment. Surgeons have been looking for a better way to diagnose rejection in recipients of face and hand transplants. Recently, scientists observed that they could detect rejection in a small sample of blood from heart and kidney transplants. The way they achieved this was to look for pieces of DNA (also called “cell-free DNA”) in the blood and calculate how much DNA is from the donor and how much from the recipient of the transplants. Scientists discovered that when a transplant patient is having rejection, the amount of pieces of DNA from the donor in the patient’s blood increases. Therefore, quantifying the amount of pieces of donor DNA are in the recipient’s blood is a good way to diagnose rejection in heart transplant patients. In this study, surgeons will test if this method of measuring donor cell-free DNA in the blood is reliable and effective at diagnosing rejection in recipients of hand and face transplants. In order to do this, surgeons will use samples of blood from the donors of face/hand transplants that were stored at the time of the operation, as well as samples of blood from the recipients of face/hand transplants that have been taking at various times after the operation, including during rejection. Surgeons will measure the amount of donor cell-free DNA in all these samples using various state-of-the-art laboratory techniques. Then, they will verify if the donor cell-free DNA in these samples is actually lower at times of no rejection, and higher at times of rejection. If this method works, it can help hundreds of thousands and possibly millions of patients in the world that have suffered from devastating injuries to the face, extremities, or abdominal wall. Rejection is the major barrier for patients to get this treatment. There is an urgent need for better methods to predict and diagnose rejection in these patients. Monitoring donor cell-free DNA in the patient’s blood during follow-up visits can be a quick, less painful way to do so.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710689
Entities
People
- Bohdan Pomahač
Organizations
- United States Army