First Blood Test To Predict Lung Transplant Rejection

MedicalResearch.com Interview with:

Sean Agbor-Enoh, M.D., Ph.D. Co-Director/Staff Clinician Laboratory of Transplantation Genomics National Heart, Lung, and Blood Institute National Institutes of Health

Dr. Agbor-Enoh

Sean Agbor-Enoh, M.D., Ph.D.
Co-Director/Staff Clinician
Laboratory of Transplantation Genomics
National Heart, Lung, and Blood Institute
National Institutes of Health

MedicalResearch.com: What is the background for this study?

Response: People who receive organ transplants may develop acute or chronic rejection, in which the body’s immune system attacks the transplanted organ. While acute rejection is treatable and reversible, chronic rejection is not and remains the most common cause for organ transplant loss. Lung transplant recipients have the shortest survival rates among patients who get solid organ transplantation of any kind—only about half live past five years. This poor survival rate among lung transplant recipients is due in part to a high incidence of chronic rejection. Existing tools for detecting signs of rejection, such as biopsy, either require the removal of small amounts of lung tissue or are not sensitive enough to discern the severity of the rejection.

Building upon earlier work, our research team developed a simple blood test that can detect when a newly transplanted lung is being rejected by a patient, even when no outward signs of the rejection are evident.  The test could make it possible for doctors to intervene faster to prevent or slow down so-called chronic rejection—which is severe, irreversible, and often deadly—in those first critical months after lung transplantation. This same test might also be useful for monitoring rejection in other types of organ transplants.

Called the donor-derived cell-free DNA test, the experimental test begins with obtaining a few blood droplets taken from the arm of the transplant recipient. A special set of machines then sorts the DNA fragments in the blood sample, and in combination with computer analysis, determines whether the fragments are from the recipient or the donor and how many of each type are present.  Because injured or dying cells from the donor release lots of donor DNA fragments into the bloodstream compared to normal donor cells, higher amounts of donor DNA indicate a higher risk for transplant rejection in the recipient.

MedicalResearch.com: What are the main findings?

Response: In our study, 106 lung transplant recipients were enrolled and monitored. Blood samples collected in the first three months after transplantation underwent the testing procedure. The results showed that those with higher levels of the donor-derived DNA fragments in the first three months of transplantation were six times more likely to subsequently develop transplant organ failure or die during the study follow-up period than those with lower donor-derived DNA levels. Importantly, we found that more than half of the high-risk subjects showed no outward signs of clinical complications during this period.

MedicalResearch.com: What should readers take away from your report? 

Response: To our knowledge, this is the first report of a reliable blood test that identifies patients at risk of developing chronic rejection and organ transplant failure. This blood test, which is still in development, could solve a long-standing problem in lung transplants: detection of hidden signs of rejection. And it detects rejection within only three months of transplantation.

Earlier detection could allow earlier intervention.  Once rejection is detected early via this test, doctors would then have the option to increase the dosages of anti-rejection drugs, add new agents that reduce tissue inflammation, or take other measures to prevent or slow the progression. We’re very excited about the potential of this test to save lives, especially in the wake of a critical shortage of donor organs.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Additional lab studies are needed as well as clinical trials. If validated, this blood test could become a routine tool to monitor transplant patients at the very early stages of rejection. 

MedicalResearch.com: Is there anything else you would like to add?

Response: This research is supported by The Genomic Research Alliance for Transplantation Study (NCT02423070), which is funded by the Division of Intramural Research of the National Heart, Lung, and Blood Institute (NHLBI). The research is also supported by The Genome Transplant Dynamics Study (NCT01985412), which is funded by the National Institute of Allergy and Infectious Diseases (NIAID) through Grant RC4AI092673. Both NHLBI and NIAID are part of the National Institutes of Health. Multiple research institutions were involved in this study.

Citation:

Donor-derived cell-free DNA predicts allograft failure and mortality after lung transplantation

https://doi.org/10.1016/j.ebiom.2018.12.029

 

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