Anti-BAFF treatment interferes with humoral responses in a model of renal transplantation in rats Background: B cell activating factor (BAFF) is associated with donor-specific antibodies (DSA) and poorer outcomes after renal transplantation (RTx). We examined the effects of anti-BAFF treatment on B cells, expression of costimulatory molecules and cytokines, germinal centers (GCs) and DSA formation in a RTx model in rats. Methods: Anti-BAFF antibody was injected on days 3, 17, 31 and 45 after allogeneic RTx. Rats received reduced dose cyclosporine A (CsA) for 28 or 56 days to allow chronic rejection and DSA formation. Leukocytes, B cell subsets and DSA were measured using flow cytometry; expression of cytokines and costimulatory molecules was measured by qRT-PCR, and GCs and T follicular helper (TfH) were assessed using immunohistochemistry. Rejection was evaluated by a nephropathologist. Results: Anti-BAFF treatment reduced the frequency of B cells in allografts and spleen. Naïve B cells were strongly reduced by anti-BAFF treatment in all compartments. mRNA expression of IL-6 and the costimulatory molecules CD40 and ICOS ligand was significantly reduced in anti-BAFF-treated rats. GCs were smaller and plasmablast/plasma cell numbers lower in anti-BAFF-treated rats, which was reflected by less DSA in certain IgG subclasses. Conclusions: Anti-BAFF treatment interferes with humoral responses at multiple levels in this model of allogeneic RTx. Authorship:LS worked on experimental design, performed data analysis and interpretation, and wrote the manuscript. HP performed treatments and operation of animals. AS assisted in data analysis. EKG assisted in data interpretation and reviewed the manuscript. KA evaluated histopathology and reviewed the manuscript. BB contributed to data interpretation and reviewed the manuscript. TB worked on experimental design, data interpretation, manuscript writing and supervised the research project. All authors approved the manuscript before submission. Disclosure: The authors of this manuscript have no conflicts of interest to disclose. Funding: This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Projektnummer 387509280 SFB 1350. This work was also supported by the Else Kröner-Fresenius-Stiftung to BT. Anti-BAFF AB was provided by donation of GSK, Stevenage, UK. Corresponding author: Louisa Steines, MD, BSc, Department of Nephrology, University Hospital Regensburg, Franz-Josef-Strauß Allee 11, 93053 Regensburg, Germany. Tel.: +49-941-9447301, Fax: +49-941-9447302, Email: Louisa.Steines@ukr.de, ORCID identifier: 0000-0002-6027-2986 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

First Report on Ex vivo Delivery of Paracrine Active Human Mesenchymal Stromal Cells to Liver Grafts During Machine Perfusion No abstract available

Brexit and transplantation research: EU funding and scientific collaborations No abstract available

“Posttransplant calcineurin inhibitors levels and intra-patient variability are not associated with long term outcomes following liver transplantation” Background: There is an interest in understanding the association between early calcineurin inhibitors (CNI) exposure post-Liver Transplantation (LT) and long-term outcomes. We aimed to analyze this association exploring median CNI levels and intrapatient-variability (IPV) in a multicenter, retrospective cohort. Methods: Tac and CsA levels obtained during the first 15 days post LT were collected. High-immunosuppression (IS) was considered as a median Tac, CsA C0 or C2 higher than 10 ng/ml, 250 ng/ml or 1200 ng/ml, respectively or a peak of Tac > 20 ng/ml. Optimal-IS was defined as a median of Tac, CsA C0 or C2 levels between 7-10 ng/ml, 150-250 ng/ml or 800-1200 ng/ml. Low-IS was defined as below the thresholds of optimal-IS. IPV was estimated during the first 15 days post-LT. Results: The study included 432 patients with a median follow up of 8.65 years. Immunosuppression regimen was based on either Tac or CsA in 243 (56.3%) and 189 (43.8%), respectively. There were no differences in terms of graft loss among low versus optimal and high-IS groups (p= 0.812 and p=0.451) nor in high vs low IPV (p=0.835). Only viral hepatitis and arterial hypertension were independently associated with higher graft loss (HR 1.729, p= 0.029 and HR 1.570, p=0.021). Conclusions: In our series, and in contrast to what has previously been reported, no association was found between very-early postoperative over-IS or high-IPV and long-term outcome measures following LT. Strategies aimed at reducing these long-term events should likely focus on other factors or on a different IS time window. Disclosure: The authors of this manuscript have no conflicts of interest to disclose. Funding: Dr. Tommaso Di Maira was financed by Rio Hortega Research Grant n.15/00133 and Juan Rodés Research Grant n. JR18/00008, supported by Instituto de Salud Carlos III. Ciberehd is partially funded by the Instituto de Salud Carlos III. Corresponding Author contact: Name/Surname: Marina Berenguer and Tommaso Di Maira, Address: Avenida Fernando Abril Martorell, 106 (Torre F5), Valencia, Spain. Telephone/Fax: +34-961 244 5859, e-mail: marina.berenguer@uv.es; dimaira@me.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Emerging role of myeloid-derived suppressor cells in the biology of transplantation tolerance MDSCs, a heterogeneous population of myeloid cells, are characterized by their immunosuppressive abilities through the secretion of various cytokines such as iNOS, NO, ROS, TGF-β, and Arg-1. Accumulating evidence highlights its potential role in maintaining immune tolerance in solid organ and hematopoietic stem cell transplantation (HSCT). Mechanistically, MDSCs induced transplant tolerance is mainly dependent on direct suppression of allogeneic reaction or strengthened crosstalk between MDSCs and Treg or NKT cells. Adopted transfer of in vitro- or in vivo-induced MDSCs by special drugs therefore becomes a potential strategy for maintaining transplantation tolerance. In this review, we will summarize the previously published data regarding the role of MDSCs in the biology of transplantation tolerance and gain insights into the possible molecular mechanism governing this process. Disclosure The authors declare that they have no conflict of interest. Funding This paper is supported by National Natural Science Foundation of China (No.81500151 & 81160074), Natural Science Foundation of Hubei Province (No.2017CFB631) and Zhongnan Hospital of Wuhan University Science, Technology and Innovation Seed Fund (No.znpy2018025). Correspondence information: Dr. Liang Shao, Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. E-mail: liangsmd@163.com Tel:+86 15871455000 Prof. Albert KW Lie, Division of Hematology & BMT Center, Queen Mary Hospital, Hong Kong, SAR China. E-mail: akwlie@hku.hk, Tel:+852 22555859, Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Safety of donation from brain-dead organ donors with central nervous system tumors: Analysis of transplantation outcomes in Korea Background: This study aims to verify the condition of recipients of solid organs from donors with central nervous system (CNS) tumors and determine the risk of disease transmission due to transplantation. Methods: Twenty-eight brain-dead organ donors with CNS tumors and 91 recipients who received solid organs from January 1, 2005, to December 31, 2014, in Korea were investigated using the Korean Network of Organ Sharing data. Results: Of the 36 recipients of organs from the 11 donors whose pathological results were not verified, four developed tumors: renal cell carcinoma, carcinoma in situ of the cervix uteri, B-cell lymphoma, and colon cancer. Among 51 recipients from 17 donors with CNS tumor, no recipient had the same tumor as the donors. Six were classified as high-risk donors according to the World Health Organization (WHO) classification, and 14 recipients from these donors did not develop tumor after transplantation. The remaining 11 donors were classified as low-risk donors according to the WHO classification but as high-risk donors according to the Malignancy Subcommittee of the Disease Transmission Advisory Committee of the Organ Procurement and Transplantation Network/United Network for Organ Sharing. Of the 37 recipients, three had recurring hepatocellular carcinoma with lung and bone metastases, thyroid cancer, and Kaposi’s sarcoma after transplantation. Conclusions: The risk of disease transmission due to organ transplantation from donors with CNS tumors was very low. Thus, organ donation from such donors should be promoted actively to expand the donor range. Funding: None Disclosure: The authors declare no conflicts of interest. Address for correspondence: Jae-myeong Lee, MD, PhD, Department of Acute Care Surgery, Korea University Anam Hospital, Korea University College of Medicine, 73, Goryeodae-ro, Seongbuk-gu, Seoul, Republic of Korea. Tel: +82-2-920-5948, Fax: +82-2-920-5948, E-mail: ljm3225@hanmail.net Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Donors with central nervous system cancer: Proceed with vigilance No abstract available

Anti-BAFF therapy: a new tool to target B cells in antibody-mediated rejection? No abstract available

Circulating donor-derived cell-free DNA as a biomarker in vascularized composite allotransplantation? No abstract available

Shorter Height is Associated with Lower Probability of Liver Transplantation in Patients with Hepatocellular Carcinoma Background: The effect of height and sex on liver transplantation (LT) for hepatocellular carcinoma (HCC) remains unclear. Methods: Using United Network for Organ Sharing (UNOS) data, 14,844 HCC patients listed for LT from 2005-2015 were identified. Cumulative incidence of waitlist events (LT and dropout for death or too sick) were calculated and modeled using Fine and Gray competing risk regression. Results: Short (SWR), Mid (MWR) and Long (LWR) UNOS wait regions comprised 25%, 42%, and 33% of the cohort. Three-year cumulative incidence of LT was lower in shorter height patients (≤150, 151-165, and >185 cm; 70.8%, 76.7%, and 83.5%, p<0.001) and women (78.2% vs 79.8%, p<0.001) and. On multivariable analysis, shorter height (≤150, 151-165 cm, HR versus >185 cm) was associated with lower probability of LT (0.81 and 0.89, p=0.02) and greater dropout (HR 1.99 and 1.43, p<0.001). Female sex was not associated with LT overall, but a significant sex and wait region interaction (p=0.006) identified lower LT probability for women in MWR (HR versus men, 0.91, p=0.02). Conclusion: Despite uniform HCC MELD exception across height and sex, shorter patients and females in MWR have lower probability of LT. Consideration should be given to awarding additional MELD exception points to these patients. Disclosures: None of the authors have any relevant potential conflicts of interest to disclose Financial Support: This work was supported by the Clinical and Translational Core of the UCSF Liver Center (P30 DK026473). Corresponding Author: Neil Mehta, M.D., University of California, San Francisco, 513 Parnassus Avenue, Room S-357, San Francisco, CA 94143-0538, E-mail: neil.mehta@ucsf.edu Tel: (415)-476-2777, Fax: (415)-476-0659 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.