Face and extremity transplantation can change the life of patients who had suffered severe body injuries, improving their quality of life, function, and social interactions. However, transplantation is not without risks. Despite the short-term successes, the high rate of acute rejection and infectious complications related to the anti-rejection medications are major concerns. Therefore, there is a need to develop better tools to identify transplant problems and to guide medication selection and dose adjustment in transplant recipients.

The current research proposal has two main objectives: (1) Develop a non-invasive blood test to serve as the "thermometer" of the immune system in order to earlier detect rejection and help medication adjustment. (2) Identify specific alarming signals in the blood that indicate injury to the transplanted organ before any clinical symptoms or signs are present.

This proposal is innovative for three main reasons: (1) It tackles a puzzling and worrisome problem of face/extremity transplants, which is the extremely high rate of acute rejection with the use of current anti-rejection medications. (2) The study will use cutting-edge technological tools to comprehend the complexity of the immune system upon VCA transplantation. (3) The availability of blood and biopsy samples of face/extremity transplanted patients in our center since 2009 will allow us to understand in detail what is happening with the immune system at different parts of the body. This is the largest collection of face/extremity transplant samples in the world and a precious resource that we wish to utilize to help improve care of current and future face/extremity transplant recipients.

This proposal addresses two main Focus Areas of this award mechanism: (1) Graft surveillance -- clinical monitoring (immune profiling). (2) Immune regulation -- optimizing immunosuppressive drug regimens.

The results of this study will allow us to better monitor transplanted patients and to personalize the selection and dosage of anti-rejection medications. Our future goal is to use these markers to aid patient management and to develop novel therapies to maximize the life of the transplanted patients.