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BMJ Open Sep 2023Kidney transplant recipients (KTRs) suffer from immunosuppression-related adverse events (iRAEs), such as infections and malignancy from chronic immunosuppression, but...
INTRODUCTION
Kidney transplant recipients (KTRs) suffer from immunosuppression-related adverse events (iRAEs), such as infections and malignancy from chronic immunosuppression, but are also at risk of graft loss from rejection with underimmunosuppression. Biomarkers that predict both iRAEs and rejection while allowing individualisation of immunosuppression exposure are lacking. Although plasma viral DNA levels of torque teno virus (TTV), a widely prevalent, non-pathogenic virus, have been shown to predict both iRAE and rejection in newly transplanted KTRs within the first year after transplant, its role for prevalent KTRs on stable immunosuppression is less clear.This study aims to determine the prognostic value of TTV levels for severe infections (defined as infections requiring hospitalisation) in prevalent KTRs on stable immunosuppression for at least 3 months and compare it against that of other commonly available biomarkers. The study also aims to explore the relationship between TTV levels and factors affecting the 'net state of immunosuppression' as well as other clinical outcomes.
METHODS AND ANALYSIS
This is a single-centre, prospective, observational cohort study of 172 KTRs on stable immunosuppression for more than 3 months. TTV levels will be measured using the TTV R-GENE kit upon recruitment when study subjects are admitted and when kidney allograft biopsies are performed. Subjects will be monitored for iRAEs and rejection for at least 12 months. The relationship between TTV load and clinical outcomes such as severe infections will be analysed and compared against that from other common biomarkers and previously published predictive scores.
ETHICS AND DISSEMINATION
The study was approved by the SingHealth Centralised Institutional Review Board (2023/2170). The results will be presented at conferences and submitted for publication in peer-reviewed journals.
TRIAL REGISTRATION NUMBER
NCT05836636.
Topics: Humans; Torque teno virus; Monitoring, Immunologic; Prospective Studies; Kidney Transplantation; Immunosuppression Therapy; Observational Studies as Topic
PubMed: 37730403
DOI: 10.1136/bmjopen-2023-076122 -
Transplantation Proceedings Mar 1979The development of liver transplantation has been made difficult because of the enormous technical difficulties of the procedure and because the postoperative management...
The development of liver transplantation has been made difficult because of the enormous technical difficulties of the procedure and because the postoperative management in early cases was defective in many instances. With surgical and medical improvements, the prospects for success have markedly increased recently. The wider use of thoracic duct fistula as an adjuvant measure during the first 1 or 2 postoperative months is being explored.
Topics: Age Factors; Biliary Tract Surgical Procedures; Histocompatibility Testing; Humans; Immunosuppression Therapy; Liver Transplantation; Tissue Preservation; Transplantation, Homologous
PubMed: 109961
DOI: No ID Found -
Transplant International : Official... Aug 2015Immunosuppressive therapy after kidney transplantation consists of a calcineurin inhibitor (CNI)-based therapy in combination with mycophenolic acid and steroids in most... (Review)
Review
Immunosuppressive therapy after kidney transplantation consists of a calcineurin inhibitor (CNI)-based therapy in combination with mycophenolic acid and steroids in most cases. In spite of low acute rejection rates and excellent graft survival, it is associated with major long-term complications, such as cardiovascular events, malignancy, and nephrotoxicity, and does not favor tolerogenic processes. Mammalian target of rapamycin (mTOR) inhibitors in combination with low-dose CNI offer good rejection rates and acceptable allograft function; however, de novo mTOR inhitibor-based treatment in combination with mycophenolate is not widely used due to higher acute rejection rates. Early conversion from a CNI to an mTOR inhibitor is a feasible option in selected patients with a slightly higher acute rejection rate, but equal or better GFR. Costimulation blockade has been proven to facilitate antirejection prophylaxis without CNI-associated side effects. So far, belatacept has been approved in combination with mycophenolate and steroids with better graft function, however, a slightly higher acute rejection rate. Recently, the combination of an mTOR inhibitor and belatacept with lymphocyte-depleting antibody induction and without maintenance steroids has been explored in two pilot studies with very low acute rejection rates, very good graft function, and an acceptable side effect profile.
Topics: Abatacept; Calcineurin Inhibitors; Drug Administration Schedule; Drug Therapy, Combination; Everolimus; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Sirolimus; TOR Serine-Threonine Kinases
PubMed: 25959589
DOI: 10.1111/tri.12603 -
Kidney360 Mar 2022
Topics: Glomerulonephritis, IGA; Humans; Immunosuppression Therapy; Immunosuppressive Agents
PubMed: 35582174
DOI: 10.34067/KID.0000512022 -
Eye (London, England) Nov 2020
Topics: Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents
PubMed: 32341535
DOI: 10.1038/s41433-020-0875-3 -
Oncoimmunology 2023Ferroptosis has gained interest due to it immunogenicity and the higher sensitivity of cancer cells to it. However, it was recently shown that ferroptosis in...
Ferroptosis has gained interest due to it immunogenicity and the higher sensitivity of cancer cells to it. However, it was recently shown that ferroptosis in tumor-associated neutrophils leads to immunosuppression and negatively impacts therapy. Here, we discuss the potential implications of the two sides (friend foe) of ferroptosis in cancer immunotherapy.
Topics: Ferroptosis; Immunotherapy; Immunosuppression Therapy; Neutrophils; Neoplasms
PubMed: 36875549
DOI: 10.1080/2162402X.2023.2182992 -
International Journal of Surgery... Nov 2015The treatment of acute liver failure, a condition with high mortality, comprises optimal clinical care, and in severe cases liver transplantation. However, there are... (Review)
Review
The treatment of acute liver failure, a condition with high mortality, comprises optimal clinical care, and in severe cases liver transplantation. However, there are limitations in availability of organ donors. Hepatocyte transplantation is a promising alternative that could fill the medical need, in particular as the bridge to liver transplantation. Encapsulated porcine hepatocytes represent an unlimited source that could function as a bioreactor requiring minimal immunosuppression. Besides patients with acute liver failure, patients with alcoholic hepatitis who are unresponsive to a short course of corticosteroids are a target for hepatocyte transplantation. In this review we present an overview of the innate immune barriers in hepatocyte xenotransplantation, including the role of complement and natural antibodies; the role of phagocytic cells and ligands like CD47 in the regulation of phagocytic cells; and the role of Natural Killer cells. We present also some illustrations of physiological species incompatibilities in hepatocyte xenotransplantation, such as incompatibilities in the coagulation system. An overview of the methodology for cell microencapsulation is presented, followed by proof-of-concept studies in rodent and nonhuman primate models of fulminant liver failure: these studies document the efficacy of microencapsulated porcine hepatocytes which warrants progress towards clinical application. Lastly, we present an outline of a provisional clinical trial, that upon completion of preclinical work could start within the upcoming 2-3 years.
Topics: Animals; Hepatocytes; Humans; Immunity, Innate; Immunosuppression Therapy; Liver Failure, Acute; Liver Transplantation; Swine; Transplantation, Heterologous
PubMed: 26361861
DOI: 10.1016/j.ijsu.2015.08.077 -
Clinical and Experimental Immunology Aug 2017In the 1960s, our predecessors won a historical battle against acute rejection and ensured that transplantation became a common life-saving treatment. In parallel with... (Review)
Review
In the 1960s, our predecessors won a historical battle against acute rejection and ensured that transplantation became a common life-saving treatment. In parallel with this success, or perhaps because of it, we lost the battle for long-lived transplants, being overwhelmed with chronic immune insults and the toxicities of immunosuppression. It is likely that current powerful treatments block acute rejection, but at the same time condemn the few circulating donor cells that would have been able to elicit immunoregulatory host responses towards the allograft. Under these conditions, spontaneously tolerant kidney recipients - i.e. patients who maintain allograft function in the absence of immunosuppression - are merely accidents; they are scarce, mysterious and precious. Several teams pursue the goal of finding a biomarker that would guide us towards the 'just right' level of immunosuppression that avoids rejection while leaving some space for donor immune cells. Some cellular assays are attractive because they are antigen-specific, and provide a comprehensive view of immune responses toward the graft. These seem to closely follow patient regulatory capacities. However, these tests are cumbersome, and require abundant cellular material from both donor and recipient. The latest newcomers, non-antigen-specific recipient blood transcriptomic biomarkers, offer the promise that a practicable and simple signature may be found that overcomes the complexity of a system in which an infinite number of individual cell combinations can lead possibly to graft acceptance. Biomarker studies are as much an objective - identifying tolerant patients, enabling tolerance trials - as a means to deciphering the underlying mechanisms of one of the most important current issues in transplantation.
Topics: Biomarkers; Host vs Graft Reaction; Humans; Immunosuppression Therapy; Kidney; Kidney Transplantation; Transplantation Tolerance; Transplantation, Homologous
PubMed: 28449211
DOI: 10.1111/cei.12981 -
Clinics in Laboratory Medicine Mar 2019There has been a prolific amount of research dedicated to the T-regulatory cells (Tregs) and their role in achieving immune homeostasis. Here, the authors briefly... (Review)
Review
There has been a prolific amount of research dedicated to the T-regulatory cells (Tregs) and their role in achieving immune homeostasis. Here, the authors briefly discuss the known biology, utilization, and potential of Tregs, for current trials and future immunotherapy. Most current trials of Treg therapies include either ex vivo expanded Tregs transferred into the peripheral blood of patients with diseases of immunologic origin or interleukin 2 injected to stimulate Tregs directly. Ongoing trials designed to measure the clinical efficacy and safety profile of these novel therapeutic approaches have resulted in largely favorable outcomes in a variety of autoimmune and alloimmune diseases.
Topics: Cell Transplantation; Immune Tolerance; Immunosuppression Therapy; Immunotherapy; Signal Transduction; T-Lymphocytes, Regulatory
PubMed: 30709499
DOI: 10.1016/j.cll.2018.11.001 -
Annals of Transplantation Nov 2016Xenotransplantation is a new technology that may help to overcome the shortage of human tissues and organs available for the treatment of tissue and organ failure.... (Review)
Review
Xenotransplantation is a new technology that may help to overcome the shortage of human tissues and organs available for the treatment of tissue and organ failure. Remarkable progress has recently been made in this field. First, understanding of the mechanisms of immunological rejection, mainly of the hyperacute rejection, allowed generating numerous genetically modified pigs to overcome rejection. Second, based on these genetically modified animals and new immunosuppression regimens, long-term survival of non-human primate recipients of heart, kidney, and islet cell cells has been reported. And third, potential zoonotic microorganisms have been identified in pigs and sensitive methods to detect them have been generated. In 2 clinical trials treating diabetic patients with porcine islet cells, no porcine microorganisms were transmitted to human recipients. Furthermore, strategies to eliminate potentially zoonotic microorganisms from donor pigs in order to prevent transmission to the recipients have been developed, including designated pathogen-free (DPF) breeding. In addition, strategies to prevent transmission of porcine endogenous retroviruses (PERVs) have been developed, including a knockout of all proviruses in the pig genome by gene editing. PERVs are integrated in the genome of all pigs and therefore they cannot be eliminated by DPF breeding. Since they are able to infect human cells, they represent a special risk in xenotransplantation. Despite the achievements, some problems remain: numerous genetically multi-modified pigs have been generated without fully evaluating their advantage, and microbiological screening of pigs to be used for transplantations and elimination of pathogenic microorganisms from the donor pigs are still not satisfactory.
Topics: Animals; Humans; Immunosuppression Therapy; Patient Safety; Swine; Transplantation, Heterologous; Zoonoses
PubMed: 27872471
DOI: 10.12659/aot.900531