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GASL Poster Prize
In: Award |Meetings written by: Prof. Dr. Igor M. Sauer
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Nathanael Raschzok's poster entitled "Serum protein biomarkers for acute rejection
in liver transplantation" was awarded with the GASL 2013 poster prize during the 29th Annual Meeting of the German Association for the Study of the Liver (GASL) in Hannover, Germany. Co-authors are Kukuh A. Prabowo, Anja Reutzel-Selke, Rosa B. Schmuck, Mehmet H. Morgul, Laura M. Tannus, Stephanie König, Sven Jonas, Peter Neuhaus, and Igor M. Sauer.


Although 20–40% of patients experience at least one episode of acute rejection (AR) after liver transplantation (LTx), diagnosis of AR is still mainly based on tissue analysis from liver biopsies. Biomarker routinely taken from blood samples would be a powerful non-invasive tool for monitoring of the liver graft status. The aim of this study was to investigate the diagnostic and prognostic value of serum protein biomarkers for acute rejection in LTx recipients. Serum samples from n=20 patients with AR and n=15 stable controls were analyzed. CXCL9 and CD31 were up-regulated in AR samples compared to controls at the time point of histologically proven rejection and at earlier time points prior rejection. Areas under the Receiver Operation Characteristics (ROC) curves were 0.6 and 0.7 at the day of rejection and 0.8 at POD1 for CXCL9 and CD31, respectively. IL-6 was increased prior and during rejection, while CD44 showed an opposite trend.
Serum protein biomarkers could be valuable for detection and prediction of AR after LTx. However, a larger number of patients, additional control groups, and prospective clinical trials will be necessary to proof the clinical utility of this diagnostic tool.

Moreover, Rosa Schmuck presented her data on "Bile: miRNA pattern and cell morphology as a diagnostic tool after liver transplantation" (co-authors: Nathanael Raschzok, Anja Reutzel-Selke, Steffen Lippert, Stephanie König, Kukuh A. Prabowo, Mehmet H. Morgul, Laura M. Tannus, Sven Jonas, Peter Neuhaus, and Igor M. Sauer) and Luisa Lisboa her work on "MicroRNA miR-352 in early liver regeneration: what role?" (co-authors: Nathanael Raschzok, Annekatrin Leder, Natalie Schlüter, Marc Jörres, Susanne Kolano, Antje Butter, Steffen Lippert, Wiebke Werner, Peter Neuhaus, and Igor M. Sauer).
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Our manuscript "Depletion of donor dendritic cells ameliorates immunogenicity of both skin and hind limb transplants" has been accepted for publication in Frontiers in Immunology, section Alloimmunity and Transplantation. Authors are Muhammad Imtiaz Ashraf, Joerg Mengwasser, Anja Reutzel-Selke, Dietrich Polenz, Kirsten Führer, Steffen Lippert, Peter Tang, Edward Michaelis, Rusan Catar, Johann Pratschke, Christian Witzel, Igor M. Sauer, Stefan G. Tullius, and Barbara Kern.

Acute cellular rejection remains a significant obstacle affecting successful outcomes of organ transplantation including vascularized composite tissue allografts (VCA). Donor antigen presenting cells (APC), particularly dendritic cells (DC), orchestrate early alloimmune responses by activating recipient effector T cells. Employing a targeted approach, we investigated the impact of donor-derived conventional DC (cDC) and APC on the immunogenicity of skin and skin-containing VCA grafts, using mouse models of skin and hind limb transplantation.
By post-transplantation day 6, skin grafts demonstrated severe rejections, characterized by predominance of recipient CD4 T cells. In contrast, hind limb grafts showed moderate rejection, primarily infiltrated by CD8 T cells. While donor depletion of cDC and APC reduced frequencies, maturation, and activation of DC in all analysed tissues of skin transplant recipients, reduction in DC activities was only observed in the spleen of hind limb recipients. Donor cDC and APC depletion did not impact all lymphocyte compartments but significantly affected CD8 T cells and activated CD4 T in lymph nodes of skin recipients. Moreover, both donor APC and cDC depletion attenuated the Th17 immune response, evident by significantly reduced Th17 (CD4+IL-17+) cells in the spleen of skin recipients and reduced levels of IL-17E and lymphotoxin-α in the serum samples of both skin and hind limb recipients. In conclusion, our findings underscore the highly immunogenic nature of skin component in VCA. The depletion of donor APC and cDC mitigates the immunogenicity of skin grafts while exerting minimal impact on VCA.

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