Grants Funded

Abstract
Despite the fact that early and intermediate functional outcomes after composite tissue allotransplantation (CTA) are highly encouraging rejection and the need for high-dose multi-drug immunosuppressive treatment continues to be the bane of CTA preventing wider clinical application. However, a better understanding of the mechanisms and identifying surrogate markers of rejection or acceptance in CTA by exploring novel methods to diagnose skin rejection could fulfill the important clinical need to enable reduction of systemic immunosuppression in CTA. This study therefore proposes to establish a non-invasive method for immune monitoring in a murine CTA model, based on novel commercially available dermal tape stripping technologies. While such methods have been used primarily in dermatology to assess skin inflammation, and other skin-related pathologies, measurement of inflammatory cytokines profiles captured in these tapes by means of Luminex might have great potential for extension of this technology into development of a clinically relevant non-invasive immune monitoring tool for acute rejection in CTA. Samples will be collected using a rat hind-limb transplantation model from both transplantated and native legs by tape stripping (Sebutape & D-Squame) and conventional skin punch biopsy. Cytokine expression profiles (protein and mRNA) will be analyzed using Luminex assays and compared between tape stripping and biopsy methods. Tissue samples will be also stained for the presence of T-lymphocytes (CD4, CD8, Foxp3), B-lymphocytes (CD20), macrophages (CD68), and other cell types that become of interest as a result of the Luminex data analysis. Selection of specific stains will consider Luminex and histology analysis results to assist in gaining the maximum mechanistic information possible. Predictive computational models for rejection, developed on existing preliminary data, will be calibrated to the data gathered by tape stripping then assessed for predictive preci

Biography
Dr. Gerald Brandacher is scientific director of the Johns Hopkins Composite Tissue Allotransplantation (CTA) program. He is also a visiting associate professor of surgery in the Department of Plastic and Reconstructive Surgery at Johns Hopkins University School of Medicine. Prior to joining Johns Hopkins in 2010, Dr. Brandacher was a key member of the hand transplant programs in Innsbruck, Austria and at the University of Pittsburgh. As scientific director of the program at UPMC he was instrumental in designing a novel cell-based immunomodulatory treatment protocol for CTA and was also part of the team performing the first bilateral hand transplant and first forearm transplant in the US. His main scientific interests are donor-specific immune tolerance and immunomonitoring strategies. Dr. Brandacher received his medical degree from Leopold Franzens University, Innsbruck, School of Medicine, and completed further surgical training at the Center of Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, at Innsbruck Medical University. He is the recipient of many national and international awards related to his work in reconstructive transplantation and the author of numerous papers, book chapters and abstracts. He is Past-President of the Austrian Society of Surgical Research, Board Member of the Composite Tissue Allotransplantation Working Group of the European Society of Organ Transplantation (ESOT), an invited member to the American Society of Transplantation (AST) and is a Founding and Scientific Advisory Board Member of the American Society of Reconstructive Transplantation (ASRT).