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Frontiers in Immunology 2020Transplantation is the gold-standard treatment for the failure of several solid organs, including the kidneys, liver, heart, lung and small bowel. The use of tailored... (Review)
Review
Transplantation is the gold-standard treatment for the failure of several solid organs, including the kidneys, liver, heart, lung and small bowel. The use of tailored immunosuppressive agents has improved graft and patient survival remarkably in early post-transplant stages, but long-term outcomes are frequently unsatisfactory due to the development of chronic graft rejection, which ultimately leads to transplant failure. Moreover, prolonged immunosuppression entails severe side effects that severely impact patient survival and quality of life. The achievement of tolerance, i.e., stable graft function without the need for immunosuppression, is considered the Holy Grail of the field of solid organ transplantation. However, spontaneous tolerance in solid allograft recipients is a rare and unpredictable event. Several strategies that include peri-transplant administration of non-hematopoietic immunomodulatory cells can safely and effectively induce tolerance in pre-clinical models of solid organ transplantation. Mesenchymal stromal cells (MSC), non-hematopoietic cells that can be obtained from several adult and fetal tissues, are among the most promising candidates. In this review, we will focus on current pre-clinical evidence of the immunomodulatory effect of MSC in solid organ transplantation, and discuss the available evidence of their safety and efficacy in clinical trials.
Topics: Animals; Humans; Immunosuppression Therapy; Mesenchymal Stem Cell Transplantation; Organ Transplantation; Transplantation Tolerance
PubMed: 33643298
DOI: 10.3389/fimmu.2020.618243 -
Pain Research & Management 2018Opioids comprise an important group of drugs used in cancer pain pharmacotherapy. In recent years, more and more studies have emerged indicating the potentially... (Review)
Review
Opioids comprise an important group of drugs used in cancer pain pharmacotherapy. In recent years, more and more studies have emerged indicating the potentially immunosuppressive effects of opioid analgesics and their serious consequences, including the risk of cancer progression. The identification of these risks has prompted a search for other effective, and most importantly, safer methods of perioperative analgesic management. Regional analgesia techniques, which allow for a significant reduction in opioid dosing and thus diminish the risk of immunosuppression associated with these drugs, seem to offer substantial hope in this respect. A number of studies available in the literature assess the effects of regional analgesia techniques on cancer progression; however, it is often difficult to interpret their results owing to several perioperative factors (such as surgical trauma, inadequate pain and stress relief, and hypothermia) which are also attributed immunosuppressive effects and tend to be implicated in increased risk of cancer progression. Further research is needed to verify the available data on both the potential adverse effects of opioids and the possible protective effects of regional analgesia techniques on cancer patients.
Topics: Analgesics, Opioid; Animals; Cancer Pain; Humans; Immunosuppression Therapy; Pain Management; Risk; Treatment Outcome
PubMed: 30327708
DOI: 10.1155/2018/9293704 -
International Journal of Molecular... Jun 2016Myelodysplastic syndrome (MDS) is a spectrum of diseases, characterized by debilitating cytopenias and a propensity of developing acute myeloid leukemia. Comprehensive... (Review)
Review
Myelodysplastic syndrome (MDS) is a spectrum of diseases, characterized by debilitating cytopenias and a propensity of developing acute myeloid leukemia. Comprehensive sequencing efforts have revealed a range of mutations characteristic, but not specific, of MDS. Epidemiologically, autoimmune diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients-especially younger low-risk patients with HLA-DR15 tissue type-demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS.
Topics: Autoimmune Diseases; Autoimmunity; Humans; Immune System; Immunity; Immunomodulation; Immunosuppression Therapy; Immunosuppressive Agents; Myelodysplastic Syndromes
PubMed: 27314337
DOI: 10.3390/ijms17060944 -
Clinical and Experimental Immunology Aug 2017
Topics: Animals; Humans; Immunosuppression Therapy; Immunotherapy, Adoptive; T-Lymphocytes, Regulatory; Transplantation Chimera; Transplantation Immunology; Transplantation Tolerance
PubMed: 28703287
DOI: 10.1111/cei.12994 -
American Journal of Transplantation :... Dec 2016
Topics: Immune Tolerance; Immunosuppression Therapy; Kidney Transplantation; Transplantation Tolerance
PubMed: 27467554
DOI: 10.1111/ajt.13993 -
Medicina (Kaunas, Lithuania) Mar 2023Achieving adequate immunosuppression for lung transplant recipients in the first year after lung transplantation is a key challenge. Prophylaxis of allograft rejection...
Achieving adequate immunosuppression for lung transplant recipients in the first year after lung transplantation is a key challenge. Prophylaxis of allograft rejection must be balanced with the adverse events associated with immunosuppressive drugs, for example infection, renal failure, and diabetes. A triple immunosuppressive combination is standard, including a steroid, a calcineurin inhibitor, and an antiproliferative compound beginning with the highest levels of immunosuppression and a subsequent tapering of the dose, usually guided by therapeutic drug monitoring and considering clinical results, bronchoscopy sampling results, and additional biomarkers such as serum viral replication or donor-specific antibodies. Balancing the net immunosuppression level required to prevent rejection without overly increasing the risk of infection and other complications during the tapering phase is not well standardized and requires repeated assessments for dose-adjustments. In our adaptive immunosuppression approach, we additionally consider results from the white blood cell counts, in particular lymphocytes and eosinophils, as biomarkers for monitoring the level of immunosuppression and additionally use them as therapeutic targets to fine-tune the immunosuppressive strategy over time. The concept and its rationale are outlined, and areas of future research mentioned.
Topics: Humans; Transplant Recipients; Immunosuppressive Agents; Immunosuppression Therapy; Biomarkers; Lung; Graft Rejection
PubMed: 36984489
DOI: 10.3390/medicina59030488 -
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 -
Indian Journal of Ophthalmology Sep 2020There are multiple approaches to inhibit inflammatory molecules and pathways in noninfectious uveitis. The cornerstone of local and systemic anti-inflammatory treatment... (Review)
Review
There are multiple approaches to inhibit inflammatory molecules and pathways in noninfectious uveitis. The cornerstone of local and systemic anti-inflammatory treatment is corticosteroid therapy. Corticosteroids remain the most potent and efficacious drugs for treating intraocular inflammation. However, their long-term use is limited by their medium- and long-term side effects, which are a major concern. The approach taken to limit corticosteroid side effects is to introduce steroid-sparing agents that suppress the inflammatory pathways and immune response differently than corticosteroids. There are several classes of such drugs that are affordable, effective, and generally well-tolerated. Relatively recently, an increasing range of biologic agents has become available to treat intraocular inflammation. However, the relatively expensive cost of these therapies limits their use in the developing world. This systemic review aimst to discuss the use of corticosteroids and different immunosuppressive regimens in the management of various uveitides.
Topics: Adrenal Cortex Hormones; Developing Countries; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Uveitis
PubMed: 32823402
DOI: 10.4103/ijo.IJO_1548_20 -
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