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tolerance in transplantation

Manan Jhaveri, Nicholas Procaccini, Kris V Kowdley
Chronic Hepatitis C is a major public health problem. The chronicity of the Hepatitis C can lead to advanced liver disease, cirrhosis and even hepatocellular carcinoma. Chronic hepatitis C is the leading indication of for liver transplantation in the United States. Since the introduction of directly acting antiviral agents (DAAs), there have been there have been dramatic advances in treatment of hepatitis C in terms of tolerability, duration of therapy with significant increases in the rates of sustained virology response (SVR)...
October 21, 2016: Minerva Gastroenterologica e Dietologica
Mª Carmen Herrero-Sánchez, Concepción Rodríguez-Serrano, Julia Almeida, Laura San Segundo, Susana Inogés, Ángel Santos-Briz, Jesús García-Briñón, Luis Antonio Corchete, Jesús F San Miguel, Consuelo Del Cañizo, Belén Blanco
BACKGROUND: Graft-versus-host disease (GvHD) remains the major obstacle to successful allogeneic hematopoietic stem cell transplantation, despite of the immunosuppressive regimens administered to control T cell alloreactivity. PI3K/AKT/mTOR pathway is crucial in T cell activation and function and, therefore, represents an attractive therapeutic target to prevent GvHD development. Recently, numerous PI3K inhibitors have been developed for cancer therapy. However, few studies have explored their immunosuppressive effect...
October 20, 2016: Journal of Hematology & Oncology
Wubing He, Lihong Chen, Lin Zheng, Liuping Luo, Lingyun Gao
BACKGROUND: Dendritic cells (DCs) and regulatory T (Treg) cells are crucial for inducing immune tolerance. However, the suppressive function of infused Treg cells and immature DCs (imDCs) following solid organ transplantation remains unclear. METHODS: ImDCs derived from DA-donor rats and Treg cells isolated from spleens of Lewis rats were prepared. A heterotopic liver transplantation model was established to examine the immune tolerance effects of infusion of Treg-imDCs, imDCs and Treg cells individually...
October 17, 2016: Molecular Immunology
Animesh Pardanani
: Disease overview:Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in one or more extra-cutaneous organs. DIAGNOSIS: The major criterion is presence of multifocal clusters of morphologically abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC expression of CD25 and/or CD2, and presence of KITD816V. Risk stratification: The 2008 World Health Organization (WHO) classification of SM has been shown to be prognostically relevant...
November 2016: American Journal of Hematology
Hidekazu Nishikii, Byung-Su Kim, Yasuhisa Yokoyama, Yan Chen, Jeanette Baker, Antonio Pierini, Maite Alvarez, Melissa Mavers, Kristina Maas-Bauer, Yuqiong Pan, Shigeru Chiba, Robert S Negrin
CD4(+)Foxp3(+) regulatory T cells (Treg) are a subpopulation of T cells, which regulate the immune system and enhance immune tolerance after transplantation. Donor-derived Treg prevent the development of lethal acute graft versus host disease (GVHD) in murine models of allogeneic hematopoietic stem cell transplantation (HCT). We recently demonstrated that a single treatment of the agonistic antibody to DR3 (Death receptor 3, αDR3) to donor mice resulted in the expansion of donor derived Treg and prevented acute GVHD, although the precise role of DR3 signaling in GVHD has not been elucidated...
October 19, 2016: Blood
Omar S Aljitawi, Soumen Paul, Avishek Ganguly, Tara L Lin, Sid Ganguly, George Vielhauer, Maegan L Capitano, Amy Cantelina, Brea Lipe, Jonathan D Mahnken, Amanda Wise, Abigale Berry, Anurag K Singh, Leyla Shune, Christopher Lominska, Sunil Abhyankar, Dennis Allin, Mary Laughlin, Joseph P McGuirk, Hal E Broxmeyer
Umbilical cord blood (UCB) engraftment is in part limited by graft cell dose, generally one log less than that of bone marrow (BM)/peripheral blood (PB) cell grafts. Strategies toward increasing hematopoietic stem/progenitor cell (HSPC) homing to BM have been assessed in order to improve UCB engraftment. Despite recent progress, a complete understanding of how HSPC homing and engraftment are regulated is still elusive. We provide evidence that blocking erythropoietin (EPO)-EPO receptor (R) signaling promotes homing to BM and early engraftment of UCB CD34(+) cells...
October 19, 2016: Blood
Jie Qin, Yusuke Arakawa, Miwa Morita, John J Fung, Shiguang Qian, Lina Lu
BACKGROUND: Islet transplantation is a promising therapeutic approach for restore the physical response to blood glucose in type 1 diabetes. Current chronic use of immunosuppressive reagents for preventing islet allograft rejection is associated with severe complications. In addition, many of the immunosuppressive drugs are diabetogenic. The induction of transplant tolerance to eliminate the dependency on immunosuppression is ideal, but remains challenging. METHODS: Addition of hepatic stellate cells allowed generation of myeloid-derived suppressor cells (MDSC) from precursors in mouse bone marrow...
October 17, 2016: Transplantation
Bowen Gao, Qingxiong Yu, Feng Xie, Lingling Sheng, Xiyuan Mao, Qingfeng Li, Hainan Zhu
BACKGROUND: Conventional reconstructive methods fail to achieve satisfactory results in total eyelid defect cases. Vascularized composite tissue allotransplantation might provide both good appearance and function for these patients. The structure of the eyelid is exceptional because it simultaneously consists of skin, connective tissue, the striated muscle, fiber structure, aponeuroses, and mucosa. Thus, before clinical application of eyelid allotransplantation, more experiments are needed to clarify the impact of ischemia, immunal suppressive agents, and deinnervation effects on these sophisticated structures...
October 13, 2016: Ophthalmic Plastic and Reconstructive Surgery
Cees van Kooten, Ton J Rabelink, Johan W de Fijter, Marlies E J Reinders
PURPOSE OF REVIEW: Progress in the improvement of short-term and long-term outcomes of kidney transplantation seems to have reached a plateau, partially due to consequences of very efficient, but nonspecific immunosuppressive drugs. In recent years, various forms of cell therapy, including the use of mesenchymal stromal cells, have been put forward as an alternative strategy for more defined therapy. It is thought that these therapies will not only allow controlled tapering of immunosuppressive medication, but might bring us also closer to the ambition of generating donor-specific immune regulation and tolerance...
October 15, 2016: Current Opinion in Organ Transplantation
Oleg O Rummo, Mario Carmellini, Lionel Rostaing, Rainer Oberbauer, Maarten H L Christiaans, Christiane Mousson, Robert M Langer, Franco Citterio, Bernard Charpentier, Malcolm Brown, Gbenga Kazeem, Frank Lehner
ADHERE was a randomized, open-label, Phase IV study comparing renal function at Week 52 post-kidney transplant, in patients who received prolonged-release tacrolimus-based immunosuppressive regimens. On days 0-27, patients received prolonged-release tacrolimus (initially 0.2mg/kg/day), corticosteroids and mycophenolate mofetil (MMF). Patients were randomized on Day 28 to receive either prolonged-release tacrolimus plus MMF (Arm 1) or prolonged-release tacrolimus (≥25% dose-reduction on Day 42) plus sirolimus (Arm 2)...
October 18, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
G Varela-Fascinetto, C Benchimol, R Reyes-Acevedo, M Genevray, D Bradley, J Ives, H T Silva
This multicenter, open-label study evaluated the tolerability of extended prophylaxis with valganciclovir in pediatric kidney transplant recipients at risk of CMV disease. Fifty-six patients aged 4 months to 16 years received once-daily valganciclovir oral solution and/or tablets, dosed by BSA and renal function, for up to 200 days. The most common AEs on treatment were upper respiratory tract infection (33.9%), urinary tract infection (33.9%), diarrhea (32.1%), leukopenia (25.0%), neutropenia (23.2%), and headache (21...
October 17, 2016: Pediatric Transplantation
Hanne Kuitunen, Susanna Tokola, Topi Siniluoto, Matti Isokangas, Eila Sonkajärvi, Seppo Alahuhta, Taina Turpeenniemi-Hujanen, Esa Jantunen, Tapio Nousiainen, Kaija Vasala, Outi Kuittinen
Primary central nervous system lymphoma (PCNSL) is a rare brain tumour with a dismal prognosis. Several phase II studies with high-dose methotrexate-based regimens have shown promising early results, but in all hospital-based data published so far, the disease outcome has been poor. Patients with relapsed or refractory disease have a dismal prognosis. We performed retrospective analysis to evaluate results and tolerabilities of BBBD therapy in combination with high-dose therapy supported by autologous stem cell transplantation...
October 17, 2016: Journal of Neuro-oncology
Yundong Qu, Ying Guo, Tao Li, Qian Ye, Chao Sun, Lei Wang, Baohua Yang
BACKGROUND AND AIM: To assess the efficacy and safety of sofosbuvir-based interferon-free therapies in liver transplantation recipients with hepatitis C virus infection recurrence. METHODS: A systematic literature search was conducted in PubMed, EMBASE, Web of Science, and CENTRAL on the Cochrane Library without time or language limitation. The search strategy used was "sofosbuvir AND transplantation". Sustained virologic response at 12 weeks after the end of treatment (SVR12) rate, incidence of serious adverse events (SAEs) and/or adverse events (AEs), discontinuation rate with 95% confidence intervals (CI) were pooled with random-effects model...
October 17, 2016: Journal of Gastroenterology and Hepatology
L Benítez-Gutiérrez, C de Mendoza, I Baños, A Duca, A Arias, A Treviño, S Requena, M J Citores, V Cuervas-Mons
New direct-acting antivirals (DAAs) have dramatically improved sustained virologic response (SVR) rates in patients treated for chronic hepatitis C. Although the safety of these agents has been very good in registration trials, unexpected side effects have been reported after much broader use of DAAs on marketing. We retrospectively examined all liver transplant recipients with chronic hepatitis C that received sofosbuvir-based regimens at our clinic. A total of 24 liver transplant recipients with recurrent chronic hepatitis C had received sofosbuvir up to April 2015...
September 2016: Transplantation Proceedings
C M Cruz, S Pereira, J Gandara, S Ferreira, V Lopes, J Daniel, H P Miranda
Calcineurin inhibitors (CNI) are the base of immunosuppressive regimens in liver transplantation but they are associated with significant side effects, namely nephrotoxicity, which leads to increased morbidity and mortality. Through time, mycophenolate mofetil (MMF) as monotherapy has been suggested as an alternative in patients with CNI-related toxicity, but still no consensus has been reached as to its efficacy. We have evaluated the safety, efficacy, and tolerability of MMF monotherapy in selected patients, developing CNI-associated events, focusing primarily on kidney dysfunction...
September 2016: Transplantation Proceedings
Cyril Garrouste, Dany Anglicheau, Nassim Kamar, Claire Bachelier, Joseph Rivalan, Bruno Pereira, Sophie Caillard, Julien Aniort, Philippe Gatault, Martin Soubrier, Johnny Sayegh, Charlotte Colosio, Anthony Buisson, Eric Thervet, Nicolas Bouvier, Anne Elisabeth Heng
Anti-tumor necrosis factor-α (TNFα) therapy has improved the prognosis of many chronic inflammatory diseases. It appears to be well-tolerated by liver-transplant patients. However, their use and their safety in kidney-transplant patients have yet to be determined.In this retrospective study, we identified 16 adult kidney-transplant patients aged 46.5 years (34-51.8) who received anti-TNFα therapy from 7 kidney transplantation centers. The indications for this treatment included: chronic inflammatory bowel disease (n = 8), inflammatory arthritis (n = 5), AA amyloidosis (n = 1), psoriasis (n = 1), and microscopic polyangiitis (n = 1)...
October 2016: Medicine (Baltimore)
Jong Man Kim, Choon Hyuck David Kwon, Jae-Won Joh, Gyu-Seong Choi, Jae Berm Park, Eun-Suk Kang, Sung Joo Kim, Suk-Koo Lee
PURPOSE: T lymphocytes are an essential component of allograft rejection and tolerance. The aims of the present study are to analyze the characteristics of T-cell subsets between ABO-incompatible living donor liver transplantation (ABO-I LDLT) and ABO-compatible LDLT (ABO-C LDLT). MATERIALS AND METHODS: Between April 2013 and June 2014, 61 patients underwent adult LDLT. ABO-I LDLT patients received rituximab and all patients received basiliximab as induction therapy and tacrolimus as maintenance therapy...
October 13, 2016: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
Daniele Muser, Pasquale Santangeli, Simon A Castro, Rajeev K Pathak, Jackson J Liang, Tatsuya Hayashi, Silvia Magnani, Fermin C Garcia, Mathew D Hutchinson, Gregory G Supple, David S Frankel, Michael P Riley, David Lin, Robert D Schaller, Sanjay Dixit, Erica S Zado, David J Callans, Francis E Marchlinski
BACKGROUND: Catheter ablation (CA) of ventricular tachycardia (VT) in patients with nonischemic dilated cardiomyopathy can be challenging because of the complexity of underlying substrates. We sought to determine the long-term outcomes of endocardial and adjuvant epicardial CA in nonischemic dilated cardiomyopathy. METHODS AND RESULTS: We examined 282 consecutive patients (aged 59±15 years, 80% males) with nonischemic dilated cardiomyopathy who underwent CA. Ablation was guided by activation/entrainment mapping for tolerated VT and pacemapping/targeting of abnormal electrograms for unmappable VT...
October 2016: Circulation. Arrhythmia and Electrophysiology
Lucy M Turner, Elena Ricevuto, Alexia Massa Gallucci, Maurizio Lorenti, Maria-Cristina Gambi, Piero Calosi
We are starting to understand the relationship between metabolic rate responses and species' ability to respond to exposure to high pCO2. However, most of our knowledge has come from investigations of single species. The examination of metabolic responses of closely related species with differing distributions around natural elevated CO2 areas may be useful to inform our understanding of their adaptive significance. Furthermore, little is known about the physiological responses of marine invertebrate juveniles to high pCO2, despite the fact they are known to be sensitive to other stressors, often acting as bottlenecks for future species success...
2016: Marine Biology
Takahiro Yamauchi
Standard induction chemotherapy regimens achieve complete remission rates of 80% in younger adult patients with acute myeloid leukemia (AML). However, because of disease relapse only 40-50% of patients achieve long-term survival. Five-year survival rates in older patients are only one third of those achieved in younger cases. The adverse prognostic impact of advanced age is attributable to the chemotherapy-resistant nature of the blasts and the limited tolerability these patients have for intensive chemotherapy...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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