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Non-Invasive Immune Monitoring Biomarkers using Plasma microRNAs in VCA

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[Technical Report, Annual Report]

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Vascularized composite allotransplantation VCA has become a viable alternative to reconstruct complex defects. In the emerging field of VCA, a critical component in the success of the graft is careful maintenance of immunosuppression. Over-immunosuppression results in chronic infections and the accumulation of dangerous side effects. On the other hand, insufficient immunosuppression can lead to acute or chronic rejection episodes and the loss of graft function or even the graft itself. When embarking on innovative new tolerance induction protocols, or attempting to wean patients from conventional therapies the ability to monitor the immunological status of an allograft is of critical importance. 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 which can detect changes in the immunological status of the graft prior to obvious clinical manifestations of inflammation and tissue damage. MicroRNAs miRNAs are single-stranded non-coding RNAs and exist in various tissues, organs and even in blood. The objective of this application is to develop some tissue specific miRNAs without the requirement for invasive tissue biopsy. Herein, Specific Aim1 propose to investigate whether profile of miRNAs differ between donor grafts. miRNAs including let 7a7c, miR-125b, miR-146, miR-150, miR-181a, miR-155, miR-144, miR-29, miR-21, miR-192, miR-142-5p and miR-223 will be compared to histopathological changes and clinical outcomes between groups. In Specific Aim2, mechanistic trends of expression in miRNAs within long term surviving and tolerant recipients will be tested. In Specific Aim3, correlation and validation in any of miRNAs in human samples will be verified any signature identified in Aim 1 and 2.

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  • Medicine and Medical Research

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[A, Approved For Public Release]