Noninvasive Immune Monitoring Biomarkers Using Plasma microRNAs in VCA
Abstract
Rationale and Objective: Nearly 40% of combat injuries sustained in Operations Iraqi Freedom and Enduring Freedom involved severe trauma to the arms, legs, and/or face. For many devastating injuries where conventional surgical reconstruction is not possible, vascularized composite allotransplantation (VCA) has become a viable alternative. The term VCA describes procedures whereby any section of the body that includes arteries and veins supplying and removing blood from an area (vascularized), along with multiple types of body tissues such as bone, muscle, and skin (composite), is transplanted from one person to another (allotransplantation). The most commonly known forms of VCA are hand and face transplantation to date. VCA is an approach that provides new, exciting options (in particular for Wounded Warriors) that can restore appearance and function better than other currently available treatments. However, the problem of immunologic rejection of transplanted tissue is a major barrier to this treatment, as the need for lifelong drug treatment to prevent this rejection is required. Moreover, it has not prevented episodes of acute rejection and requires continuous administration of multiple immunosuppressive drugs. Direct clinical observation of transplanted hands and faces allows the detection of erythema, swelling, and inflammation. It also allows easy access for direct tissue biopsies at the first sign of acute rejection. Confirmation of clinical rejection still requires the use of an invasive biopsy, which is not ideal for routine monitoring. There exists a need for non-invasive technologies that can detect these changes in the immunological status of the graft prior to obvious clinical manifestations of inflammation and tissue damage. The overall goal of this proposal will be non-invasive immune monitoring biomarkers using plasma miRNAs. This will be consistent and directly responsive to the FY18 RTRP Concept Award Focus Areas of “Reduce the risks of VCA-associated immunotherapy” and “Identify and/or validate new peripheral biomarkers for early acute and chronic rejection.” Applicability of the Proposed Research: Hand and face transplantations are a clinical reality. However, the necessary use of anti-rejection drugs to guarantee survival of the VCA comes with a considerable toll on human health due to increased risks for cancer and infection. This research proposal suggests the use of microRNAs as a biomarker to allow detection of rejection prior to clinical manifestation. Thereby, these biomarkers would positively affect the fine-tuning of individual immunosuppression to prevent any potential side effect. This will furthermore aid in real-time point-of-care analysis and the decision-making process of weaning immunosuppression in VCA patients, including Wounded Warriors and Veterans, and in turn improve the safety, clinical success, and life-enhancing benefits of these reconstructive modalities. In addition, knowledge gained through this project will advance the field of transplant immunology and thereby serve to build greater experience not only for VCA, but also for solid organ transplantation, further increasing the potentially lifesaving impact of this new strategy.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910234
Entities
People
- Byoung Chol Oh
Organizations
- Johns Hopkins University
- United States Army