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Transplant Immunology

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https://www.readbyqxmd.com/read/28802588/t-cell-costimulation-blockade-promotes-transplantation-tolerance-in-combination-with-sirolimus-and-post-transplantation-cyclophosphamide-for-haploidentical-transplantation-in-children-with-severe-aplastic-anemia
#1
Sarita Rani Jaiswal, Prakash Bhakuni, Shamsuz Zaman, Satish Bansal, Priyanka Bharadwaj, Sneh Bhargava, Suparno Chakrabarti
We conducted a pilot study employing extended T cell costimulation blockade (COSBL) with Abatacept along with sirolimus and post-transplantation cyclophosphamide (PTCy) in 10 patients (median age 12) with severe aplastic anemia (SAA). Nine patients engrafted in the COSBL group, compared to all 10 patients (median 14 vs 13days) treated on PTCy protocols without abatacept (CONTROL group). The incidence of acute graft-versus-host disease (GVHD) was 10.5% in the COSBL group compared to 50% in the CONTROL group (p=0...
August 9, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28802587/pre-transplant-infusion-of-donor-derived-dendritic-cells-maintained-at-the-immature-stage-by-sinomenine-increases-splenic-foxp3-tregs-in-recipient-rats-after-renal-allotransplantation
#2
Lian Li, Zhigang Luo, Zhe Song, Liwen Zheng, Tuo Chen
OBJECTIVE: The immunosuppressive mechanism of sinomenine in organ allotransplantation was investigated, especially its effect of blocking dendritic cell (DC) maturation, which might influence the frequency of regulatory T cells (Tregs). METHODS: Bone marrow cells from male donor Wistar rats were induced to differentiate into DCs in vitro in the presence or absence of sinomenine, and characterized by flow cytometry. These two groups of DCs were respectively injected into male recipient Sprague-Dawley rats via the tail vein, at both high and low doses...
August 9, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28797737/nkt-cells-are-important-mediators-of-hepatic-ischemia-reperfusion-injury
#3
James A Richards, Stephen J Wigmore, Stephen M Anderton, Sarah E M Howie
INTRODUCTION: IRI results from the interruption then reinstatement of an organ's blood supply, and this poses a significant problem in liver transplantation and resectional surgery. In this paper, we explore the role T cells play in the pathogenesis of this injury. MATERIALS & METHODS: We used an in vivo murine model of warm partial hepatic IRI, genetically-modified mice, in vivo antibody depletion, adoptive cell transfer and flow cytometry to determine which lymphocyte subsets contribute to pathology...
August 7, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28782692/deleterious-impact-of-c3d-binding-donor-specific-anti-hla-antibodies-after-pediatric-liver-transplantation
#4
Eduardo Couchonnal, Christine Rivet, Stéphanie Ducreux, Jérôme Dumortier, Alexie Bosch, Olivier Boillot, Sophie Collardeau-Frachon, Rémi Dubois, Valérie Hervieu, Patrice André, Jean-Yves Scoazec, Alain Lachaux, Valérie Dubois, Olivier Guillaud
BACKGROUND: The prevalence and clinical impact of anti-HLA donor-specific antibodies (DSA) after liver transplantation (LT) have not been extensively studied, especially in pediatric population. METHODS: The present cross-sectional study included 100 patients who underwent a first LT in childhood. Anti HLA immunization study was performed at a single time point during routine follow-up using Luminex® single antigen tests with classical anti-IgG conjugate and anti-C3d conjugate...
August 3, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28778713/adipose-derived-mesenchymal-stem-cells-promote-liver-regeneration-and-suppress-rejection-in-small-for-size-liver-allograft
#5
Wei Gao, Luzhou Zhang, Yanyan Zhang, Chao Sun, Xiaobo Chen, Yuliang Wang
Adipose-derived mesenchymal stem cells (ADSCs) possess a liver regeneration capacity and immunosuppressive activity and hold promise in autologous cell-based technology. This study aimed to determine whether autologous ADSCs can improve outcomes in the rat reduced size liver transplantation model. Allogeneic 50% orthotopic liver transplantation followed by administration of autologous ADSCs delivered into the portal vein system was conducted in LEW donor rats and BN recipient rats with phosphate buffered solution (PBS) infusion used as the control...
August 1, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28757398/high-expression-of-tim-3-and-kim-1-in-blood-and-urine-of-renal-allograft-rejection-patients
#6
Sanaz Keshavarz Shahbaz, Fatemeh Pourrezagholi, Mehri Barabadi, Farshad Foroughi, Morteza Hosseinzadeh, Pedram Ahmadpoor, Mohesn Nafar, Mir Saeed Yekaninejad, Aliakbar Amirzargar
BACKGROUND: T cell immunoglobulin and mucin domain 3 (TIM-3) is involved in alloimmune and autoimmune responses, as well as tolerance induction in kidney transplantation. Kidney injury molecule-1 (KIM-1) is highly expressed in epithelial cells of the injured proximal tubule. In this study, we have investigated both urinary and blood TIM-3 mRNA expressions, urinary KIM-1 mRNA expression, and urinary and serum KIM-1 proteins in renal allograft recipients diagnosed with acute allograft rejection (AR) and chronic allograft dysfunction (CAD), as well as those with well-functioning transplants (WFG)...
July 27, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28757397/low-utility-of-serum-25-hydroxyvitamin-d3-and-1-25-dihydroxyvitamin-d3-in-predicting-peripheral-treg-and-th17-cell-counts-in-esrd-and-renal-transplant-patients
#7
Mostafa G Aly, Li Zhu, Rolf Weimer, Gerhard Opelz, Christian Morath, Ruben Kuon, Mohammed Tohamy, Gamal Saadi, Mona Soliman, Walaa Ibrahim, Volker Daniel
BACKGROUND: Vitamin D has shown an immune-modulatory effect in different studies. Vitamin D stimulates Tregs and inhibits Th17 cells. The immune-modulatory role of vitamin D in chronic kidney disease (CKD) and renal transplant patients is unclear. We measured whether different serum levels of vitamin D were associated with an increased or decreased presence of lymphocyte subsets including Treg and Th17 cells in end-stage renal disease (ESRD) and renal transplant recipients. METHODS: Eighty-seven renal transplant recipients and 53 end-stage renal disease (ESRD) patients were enrolled in this study...
July 27, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28716663/time-course-of-plasma-inflammatory-mediators-in-a-rat-model-of-brain-death
#8
Majid Esmaeilzadeh, Mahmoud Sadeghi, Roland Galmbacher, Volker Daniel, Jürgen Knapp, Hans E Heissler, Joachim K Krauss, Arianeb Mehrabi
BACKGROUND: Brain death (BD) is a donor-associated risk factor that negatively affects transplantation outcome. The inflammation associated with BD appears to have a negative effect on organ quality. Complement activation, apoptosis, and pro-inflammatory cytokine and chemokine expression are significantly increased after BD. To better understand this process, we investigated plasma chemokine and cytokine levels for 8h after BD in a rodent model. METHODS: Thirteen healthy adult male Sprague Dawley rats were intubated and mechanically ventilated...
July 15, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28687251/associations-between-acute-gvhd-related-biomarkers-and-endothelial-cell-activation-after-allogeneic-hematopoietic-stem-cell-transplantation
#9
Shosaku Nomura, Kazuyoshi Ishii, Shinya Fujita, Aya Nakaya, Atsushi Satake, Tomoki Ito
BACKGROUND: Hematopoietic stem cell transplantation (HSCT) can cause serious transplant-related complications such as graft-versus-host disease (GVHD). Acute GVHD (aGVHD) has been diagnosed by clinical manifestations, laboratory data and pathological effects until now, but recently the discovery of specific biomarkers such as suppression of tumorigenicity 2 (ST2), elafin and regenerating islet-derived 3α (REG3α) is challenging this approach. METHODS: We investigated the expression of aGVHD-related markers (regulated on activation normal T-cell expressed and secretes: RANTES, elafin, REG3α and ST2) and endothelial cell activation markers (soluble vascular cell adhesion molecule: sVCAM-1 and plasminogen activator inhibitor: PAI-1) in patients undergoing allogeneic HSCT...
July 4, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28676335/thymoglobuline-plus-basiliximab-a-mixed-cocktail-to-start
#10
EDITORIAL
Gionata Spagnoletti, Maria Paola Salerno, Rosaria Calia, Jacopo Romagnoli, Franco Citterio
Recent results reported by Ciancio et al. have demonstrated the long term successful use of dual induction therapy in kidney transplant recipients. Our experience using an "induction cocktail", thymoglobuline plus basiliximab, started in 2007 and we have treated 235 patients through the past 10years. In our population, we used a combination of CNIs and MMF or mTORi as maintenance therapy. Our results in term of patient and graft survival, acute rejection rate, renal function and incidence of post-transplant lymphoproliferative disorder support the data reported by Ciancio...
July 1, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28652007/cytokines-affecting-cd4-t-regulatory-cells-in-transplant-tolerance-iii-interleukin-5-il-5-promotes-survival-of-alloantigen-specific-cd4-t-regulatory-cells
#11
Bruce M Hall, Karren M Plain, Giang T Tran, Nirupama D Verma, Catherine M Robinson, Masaru Nomura, Rochelle Boyd, Suzanne J Hodgkinson
CD4(+)T cells mediate antigen-specific allograft tolerance, but die in culture without activated lymphocyte derived cytokines. Supplementation of the media with cytokine rich supernatant, from ConA activated spleen cells, preserves the capacity of tolerant cells to transfer tolerance and suppress rejection. rIL-2 or rIL-4 alone are insufficient to maintain these cells, however. We observed that activation of naïve CD4(+)CD25(+)FOXP3(+)Treg with alloantigen and the Th2 cytokine rIL-4 induces them to express interleukin-5 specific receptor alpha (IL-5Rα) suggesting that IL-5, a Th2 cytokine that is produced later in the immune response may promote tolerance mediating Treg...
June 23, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28642130/mir-155-expression-is-downregulated-in-kidney-transplant-patients-with-human-cytomegalovirus-infection
#12
Massimiliano Bergallo, Stefano Gambarino, Paola Montanari, Valentina Daprà, Marco Rassu, Ilaria Galliano, Paolo Ravanini
MicroRNAs are small, noncoding RNAs that control expression of target genes through inhibiting protein translation or inducing degradation of mRNA transcripts of target genes. According to the latest update, 2578 unique mature miRNAs are currently annotated in the human genome and participate in the regulation of multiple events, such as cellular proliferation or apoptosis. Herpesvirus family comprehends many viruses able to control and modulate host-cell processes permitting the survival by a latency phase after primary infection...
June 19, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28629951/immunogenicity-of-class-i-hla-but-not-preformed-low-mfi-donor-specific-antibodies-correlates-with-outcomes-after-first-renal-transplantation
#13
A Lobashevsky, W Goggins, K Rosner, T Taber
BACKGROUND: The role of low levels of circulating donor specific antibodies (DSA) producing negative flow cytometry cross match is not completely defined. The purpose of this study was to examine the clinical significance of preexisting low levels of class I DSAs in flow cytometry cross match (FC CM) negative first kidney transplant recipients (KTRs). METHODS: All of the KTRs (n=41) had low levels of anti-class I antibodies only. The kidney transplant outcome was evaluated by the development of a deleterious effect (DE) in recipients in the study cohort (Group 1: DE+, Group 2: DE-)...
June 16, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28457921/serum-mirnas-as-potential-biomarkers-for-the-bronchiolitis-obliterans-syndrome-after-lung-transplantation
#14
K Budding, M Rossato, E A van de Graaf, J M Kwakkel-van Erp, T R D J Radstake, H G Otten
Lung transplantation (LTx) is the last treatment for patients suffering from end-stage lung diseases. Survival post-LTx is hampered by the development of the bronchiolitis obliterans syndrome (BOS) and diagnosis is often late. Given the urgent clinical need to recognize BOS patients at an early stage, we analyzed circulating miRNAs to identify possible stratification markers for BOS development post-transplantation. Therefore, pro-fibrotic (miR-21, miR-155), anti-fibrotic (miR-29a) and fibrosis-unrelated (miR-103, miR-191) miRNAs were analyzed in serum of end-stage lung disease patients and during LTx follow-up...
June 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28457920/antibody-response-to-hbv-vaccination-on-dialysis-does-not-correlate-with-the-development-of-denovo-anti-hla-antibodies-after-renal-transplantation
#15
Teresa Kauke, Maximilian Link, Markus Rentsch, Manfred Stangl, Markus Guba, Joachim Andrassy, Jens Werner, Bruno Meiser, Michael Fischereder, Antje Habicht
BACKGROUND: Response to Hepatitis B virus (HBV) vaccination can be diminished in some (50-80%) but not all dialysis patients. We hypothesized, that the response to vaccination on dialysis may correlate with the development of anti-HLA antibodies after renal transplantation and might therefore be a valuable parameter to predict alloresponses. METHODS: The response to HBV vaccination on dialysis and the development of deNovo anti-HLA antibodies post-transplant was analyzed in 188 non-immunized renal transplant recipients...
June 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28366698/steroid-free-immunosuppression-is-associated-with-enhanced-th1-transcripts-in-kidney-transplantation
#16
Petra Hruba, Irena Tycova, Eva Krepsova, Eva Girmanova, Alena Sekerkova, Janka Slatinska, Ilja Striz, Eva Honsova, Ondrej Viklicky
BACKGROUND: Steroid avoidance in immunosuppression in kidney transplantation offers several metabolic advantages, however it is associated with higher early acute rejection rate. Cellular and molecular mechanisms of this phenomenon remain poorly understood. METHODS: In this single center observational study, low-risk kidney transplant recipients randomized into large multicenter prospective ADVANCE trial with steroid avoidance/early withdrawal and center standard of care treated patients were monitored for 12months...
June 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28495618/a-model-of-acute-renal-allograft-rejection-in-outbred-yorkshire-piglets
#17
Randi Lassiter, Youli Wang, Xuexiu Fang, Matt Winn, Arina Ghaffari, Chak-Sum Ho, Sandra Helman, Ryan Jajosky, Daniel Kleven, N Stanley Nahman, Todd D Merchen
Pigs represent a desirable animal model for the study of rejection in kidney transplantation with inbred Yucatan miniature swine (YMS) the most commonly studied strain due to well defined swine leukocyte antigen (SLA) genotypes. However, limitations to YMS may include cost and availability. Outbred Yorkshire pigs are widely available and significantly cheaper than YMS. Recent advances in SLA genotyping have allowed its application to outbred strains. On this basis, we theorized that Yorkshire pigs would be a viable alternative to YMS for the study of rejection in kidney transplantation...
May 8, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28487238/the-recipient-ccr5-variation-predicts-survival-outcomes-after-bone-marrow-transplantation
#18
Tomohiro Horio, Shohei Mizuno, Kaori Uchino, Motonori Mizutani, Ichiro Hanamura, J Luis Espinoza, Makoto Onizuka, Koichi Kashiwase, Yasuo Morishima, Takahiro Fukuda, Yoshihisa Kodera, Noriko Doki, Koichi Miyamura, Takehiko Mori, Akiyoshi Takami
The chemokine receptor CCR5 plays roles in the trafficking of effector cells towards the site of inflammation. We retrospectively examined the impact of the CCR5 variation (rs1800023, -2086A>G) on transplant outcomes in a cohort of 329 patients who underwent unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies through the Japan Marrow Donor Program. A multivariate analysis showed that the recipient CCR5 -2086A/A genotype was significantly associated with a lower relapse rate but not with the development of graft-versus-host disease (GVHD) or transplant-related mortality, thereby resulting in better disease-free and overall survival rates than other variations...
May 6, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28487237/cytokines-affecting-cd4-t-regulatory-cells-in-transplant-tolerance-ii-interferon-gamma-ifn-%C3%AE-promotes-survival-of-alloantigen-specific-cd4-t-regulatory-cells
#19
Masaru Nomura, Suzanne J Hodgkinson, Giang T Tran, Nirupama D Verma, Catherine Robinson, Karren M Plain, Rochelle Boyd, Bruce M Hall
CD4(+)T cells that transfer alloantigen-specific transplant tolerance are short lived in culture unless stimulated with specific-donor alloantigen and lymphocyte derived cytokines. Here, we examined if IFN-γ maintained survival of tolerance transferring CD4(+)T cells. Alloantigen-specific transplant tolerance was induced in DA rats with heterotopic adult PVG heart allografts by a short course of immunosuppression and these grafts functioned for >100days with no further immunosuppression. In previous studies, we found the CD4(+)T cells from tolerant rats that transfer tolerance to an irradiated DA host grafted with a PVG heart, lose their tolerance transferring ability after 3days of culture, either with or without donor alloantigen, and effect rejection of specific-donor grafts...
May 6, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28438668/non-neuronal-neuropeptide-y-and-its-receptors-during-acute-rejection-of-rat-pulmonary-allografts
#20
Jessica Schmitz, Anna Zakrzewicz, Sigrid Wilker, Jitka Kuncová, Andreas Hecker, Veronika Grau, Winfried Padberg, Julia P N Holler
This study tested the hypothesis that neuropeptide Y (NPY) and NPY receptors 1 (Y1) and 2 (Y2) participate in lung allograft rejection. Inflammation in grafts may include interaction between blood leukocytes and graft endothelial cells and marked accumulation of intravascular blood leukocytes. Fewer leukocytes accumulate in lung than in kidney allografts. Lung transplantion was performed in the Dark Agouti to Lewis rat strain combination. Intravascular and intraalveolar leukocytes were isolated from the grafts, and we evaluated the mRNA expression of NPY, Y1, and Y2 by real-time RT-PCR as well as the peptide expression of NPY by radioimmunoassay and immunohistochemistry...
April 21, 2017: Transplant Immunology
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