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Best Practice & Research. Clinical... 2021The innate and adaptive immune systems work as a complex interplay between different cell types, involving cytokines and chemokines mediating extracellular and paracrine... (Review)
Review
The innate and adaptive immune systems work as a complex interplay between different cell types, involving cytokines and chemokines mediating extracellular and paracrine effects. At the intracellular level, the inflammatory cascade is mediated by multifaceted processes that have been better described in the last 10 years. Immunosuppressive agents available in clinical practice act at different points of those cascades at the intracellular or extracellular level. Those drugs can mediate their effects on one or more cell types finally limiting inflammation and immune responses to antigens. Every immunosuppressive agent is characterized by intrinsic toxicity and side effects that may be due to the same therapeutic pathways or to off-target secondary effect of each molecule. We will here review the mechanisms of action of the most widely used immunosuppressive agents in the field of solid organ transplantation and autoimmune disorders, describing the mechanisms underlying both the therapeutic and secondary effects.
Topics: Autoimmune Diseases; Humans; Immune System; Immunosuppressive Agents; Organ Transplantation; Pharmaceutical Preparations
PubMed: 34874841
DOI: 10.1016/j.bpg.2021.101757 -
Nature Reviews. Nephrology Aug 2021Although overall donation and transplantation activity is higher in Europe than on other continents, differences between European countries in almost every aspect of... (Review)
Review
Although overall donation and transplantation activity is higher in Europe than on other continents, differences between European countries in almost every aspect of transplantation activity (for example, in the number of transplantations, the number of people with a functioning graft, in rates of living versus deceased donation, and in the use of expanded criteria donors) suggest that there is ample room for improvement. Herein we review the policy and clinical measures that should be considered to increase access to transplantation and improve post-transplantation outcomes. This Roadmap, generated by a group of major European stakeholders collaborating within a Thematic Network, presents an outline of the challenges to increasing transplantation rates and proposes 12 key areas along with specific measures that should be considered to promote transplantation. This framework can be adopted by countries and institutions that are interested in advancing transplantation, both within and outside the European Union. Within this framework, a priority ranking of initiatives is suggested that could serve as the basis for a new European Union Action Plan on Organ Donation and Transplantation.
Topics: Europe; European Union; Humans; Kidney Transplantation; Organ Transplantation; Stakeholder Participation; Tissue and Organ Procurement; Waiting Lists
PubMed: 33953367
DOI: 10.1038/s41581-021-00425-3 -
Clinical Infectious Diseases : An... Oct 2021Successful solid organ transplantation reflects meticulous attention to the details of immunosuppression, balancing risks for graft rejection against risks for... (Review)
Review
Successful solid organ transplantation reflects meticulous attention to the details of immunosuppression, balancing risks for graft rejection against risks for infection. The "net state of immune suppression" is a conceptual framework of all factors contributing to infectious risk. Assays that measure immune function in the immunosuppressed transplant recipient relative to infectious risk and allograft function are lacking. The best measures of integrated immune function may be quantitative viral loads to assess the individual's ability to control latent viral infections. Few studies address adjustment of immunosuppression during active infections; thus, confronted with infection in solid organ recipients, the management of immunosuppression is based largely on clinical experience. This review examines known measures of immune function and the immunologic effects of common immunosuppressive drugs and available studies reporting modification of drug regimens for specific infections. These data provide a conceptual framework for the management of immunosuppression during infection in organ recipients.
Topics: Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Infections; Organ Transplantation
PubMed: 32803228
DOI: 10.1093/cid/ciaa1189 -
The Journal of Infectious Diseases Mar 2020This review focuses on recent advances in the field of cytomegalovirus (CMV). The 2 main strategies for CMV prevention are prophylaxis and preemptive therapy.... (Review)
Review
This review focuses on recent advances in the field of cytomegalovirus (CMV). The 2 main strategies for CMV prevention are prophylaxis and preemptive therapy. Prophylaxis effectively prevents CMV infection after solid organ transplantation (SOT) but is associated with high rates of neutropenia and delayed-onset postprophylaxis disease. In contrast, preemptive therapy has the advantage of leading to lower rates of CMV disease and robust humoral and T-cell responses. It is widely used in hematopoietic cell transplant recipients but is infrequently utilized after SOT due to logistical considerations, though these may be overcome by novel methods to monitor CMV viremia using self-testing platforms. We review recent developments in CMV immune monitoring, vaccination, and monoclonal antibodies, all of which have the potential to become part of integrated strategies that rely on viral load monitoring and immune responses. We discuss novel therapeutic options for drug-resistant or refractory CMV infection, including maribavir, letermovir, and adoptive T-cell transfer. We also explore the role of donor factors in transmitting CMV after SOT. Finally, we propose a framework with which to approach CMV prevention in the foreseeable future.
Topics: Antiviral Agents; Clinical Decision-Making; Cytomegalovirus; Cytomegalovirus Infections; Disease Management; Disease Susceptibility; Hematopoietic Stem Cell Transplantation; Humans; Neutropenia; Organ Transplantation; Pre-Exposure Prophylaxis; Time Factors; Tissue Donors; Transplant Recipients; Viral Vaccines
PubMed: 32134486
DOI: 10.1093/infdis/jiz454 -
Viruses Apr 2021As guest editors, we are pleased to present this Special Issue on BK virus (BKV) and transplantation with the intention of exploring some aspects related to...
As guest editors, we are pleased to present this Special Issue on BK virus (BKV) and transplantation with the intention of exploring some aspects related to BKV-associated diseases in transplant recipients, since they are still unclear [...].
Topics: BK Virus; Disease Susceptibility; Humans; Kidney Transplantation; Organ Transplantation; Polyomavirus Infections; Transplant Recipients; Tumor Virus Infections
PubMed: 33922350
DOI: 10.3390/v13050733 -
Frontiers in Immunology 2022Transplantation is often the last resort for end-stage organ failures, e.g., kidney, liver, heart, lung, and pancreas. The shortage of donor organs is the main limiting... (Review)
Review
Transplantation is often the last resort for end-stage organ failures, e.g., kidney, liver, heart, lung, and pancreas. The shortage of donor organs is the main limiting factor for successful transplantation in humans. Except living donations, other alternatives are needed, e.g., xenotransplantation of pig organs. However, immune rejection remains the major challenge to overcome in xenotransplantation. There are three different xenogeneic types of rejections, based on the responses and mechanisms involved. It includes hyperacute rejection (HAR), delayed xenograft rejection (DXR) and chronic rejection. DXR, sometimes involves acute humoral xenograft rejection (AHR) and cellular xenograft rejection (CXR), which cannot be strictly distinguished from each other in pathological process. In this review, we comprehensively discussed the mechanism of these immunological rejections and summarized the strategies for preventing them, such as generation of gene knock out donors by different genome editing tools and the use of immunosuppressive regimens. We also addressed organ-specific barriers and challenges needed to pave the way for clinical xenotransplantation. Taken together, this information will benefit the current immunological research in the field of xenotransplantation.
Topics: Animals; Graft Rejection; Heterografts; Humans; Organ Transplantation; Swine; Tissue Donors; Transplantation, Heterologous
PubMed: 35967435
DOI: 10.3389/fimmu.2022.928173 -
American Journal of Transplantation :... Feb 2022COVID-19 vaccination mandates: A patient’s view from the transplant trenches (see Kates et al. and Hippen, pages 371 and 381).
COVID-19 vaccination mandates: A patient’s view from the transplant trenches (see Kates et al. and Hippen, pages 371 and 381).
Topics: Humans; Organ Transplantation; Transplant Recipients; Transplants; Vaccines
PubMed: 34860466
DOI: 10.1111/ajt.16908 -
Current Opinion in Organ Transplantation Aug 2020Transplant pathology contributes substantially to personalized treatment of organ allograft recipients. Rapidly advancing next-generation human leukocyte antigen (HLA)... (Review)
Review
PURPOSE OF REVIEW
Transplant pathology contributes substantially to personalized treatment of organ allograft recipients. Rapidly advancing next-generation human leukocyte antigen (HLA) sequencing and pathology are enhancing the abilities to improve donor/recipient matching and allograft monitoring.
RECENT FINDINGS
The present review summarizes the workflow of a prototypical patient through a pathology practice, highlighting histocompatibility assessment and pathologic review of tissues as areas that are evolving to incorporate next-generation technologies while emphasizing critical needs of the field.
SUMMARY
Successful organ transplantation starts with the most precise pratical donor-recipient histocompatibility matching. Next-generation sequencing provides the highest resolution donor-recipient matching and enables eplet mismatch scores and more precise monitoring of donor-specific antibodies (DSAs) that may arise after transplant. Multiplex labeling combined with hand-crafted machine learning is transforming traditional histopathology. The combination of traditional blood/body fluid laboratory tests, eplet and DSA analysis, traditional and next-generation histopathology, and -omics-based platforms enables risk stratification and identification of early subclinical molecular-based changes that precede a decline in allograft function. Needs include software integration of data derived from diverse platforms that can render the most accurate assessment of allograft health and needs for immunosuppression adjustments.
Topics: HLA Antigens; Histocompatibility Testing; Humans; Organ Transplantation; Precision Medicine; Tissue Donors; Transplantation Immunology; Transplantation, Homologous; Transplants
PubMed: 32520786
DOI: 10.1097/MOT.0000000000000772 -
Presse Medicale (Paris, France : 1983) Dec 2022The COVID-19 pandemic affects the transplant recipients since March 2020. Transplant centers quickly organized themselves to optimize the management of the...
The COVID-19 pandemic affects the transplant recipients since March 2020. Transplant centers quickly organized themselves to optimize the management of the immunocompromised patients and to progress in the knowledge of this new disease. To this end, a French Registry was created, which includes all solid organ transplant patients who have developed a SARS Cov2 infection. Numerous studies have been carried out using these data to describe this new disease in transplant patients, to characterize its clinical and biological risk factors and to define its prognosis. The 60 days-mortality of transplant patients hospitalized for COVID-19 was evaluated at 23% and renal failure plays a major role in the poor prognosis in addition to the classical risk factors described in the general population. The advent of vaccination has been a great relief but transplanted patients have shown a poor vaccine response keeping them at risk of severe disease even after an adapted vaccination scheme. Specific strategies was proposed in this particularly fragile population like increasing vaccine doses or using anti SARS Cov-2 monoclonal antibodies.
Topics: Humans; Kidney Transplantation; Pandemics; COVID-19; Organ Transplantation; Immunocompromised Host
PubMed: 36347343
DOI: 10.1016/j.lpm.2022.104146 -
Advances in Chronic Kidney Disease Nov 2021Diabetes mellitus (DM) is one of the most common complications after kidney transplantation and is associated with unfavorable outcomes including death. DM can be... (Review)
Review
Diabetes mellitus (DM) is one of the most common complications after kidney transplantation and is associated with unfavorable outcomes including death. DM can be present before transplant but post-transplant DM (PTDM) refers to diabetes that is diagnosed after solid organ transplantation. Despite its high prevalence, optimal treatment to prevent complications of PTDM is unknown. Medical therapy of pre-existent DM or PTDM after transplant is challenging because of frequent interactions between antidiabetic and immunosuppressive agents. There is also frequent need for medication dose adjustments due to residual kidney disease and a higher risk of medication side effects in patients treated with immunosuppressive agents. Sodium-glucose cotransporter 2 inhibitors have demonstrated a favorable cardio-renal profile in patients with DM without a transplant and hence hold great promise in this patient population although there is concern about the higher risk of urinary tract infections. The significant gaps in our understanding of the pathophysiology, diagnosis, and management of DM after kidney transplantation need to be urgently addressed.
Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Immunosuppressive Agents; Kidney Transplantation; Organ Transplantation
PubMed: 35367028
DOI: 10.1053/j.ackd.2021.10.004