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Progress in Retinal and Eye Research Jan 2021The search for alternatives to allotransplants is driven by the shortage of corneal donors and is demanding because of the limitations of the alternatives. Indeed,... (Review)
Review
The search for alternatives to allotransplants is driven by the shortage of corneal donors and is demanding because of the limitations of the alternatives. Indeed, current progress in genetically engineered (GE) pigs, the introduction of gene-editing technology by clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9, and advanced immunosuppressants have made xenotransplantation a possible option for a human trial. Porcine corneal xenotransplantation is considered applicable because the eye is regarded as an immune-privileged site. Furthermore, recent non-human primate studies have shown long-term survival of porcine xenotransplants in keratoplasty. Herein, corneal immune privilege is briefly introduced, and xenogeneic reactions are compared with allogeneic reactions in corneal transplantation. This review describes the current knowledge on special issues of xenotransplantation, xenogeneic rejection mechanisms, current immunosuppressive regimens of corneal xenotransplantation, preclinical efficacy and safety data of corneal xenotransplantation, and updates of the regulatory framework to conduct a clinical trial on corneal xenotransplantation. We also discuss barriers that might prevent xenotransplantation from becoming common practice, such as ethical dilemmas, public concerns on xenotransplantation, and the possible risk of xenozoonosis. Given that the legal definition of decellularized porcine cornea (DPC) lies somewhere between a medical device and a xenotransplant, the preclinical efficacy and clinical trial data using DPC are included. The review finally provides perspectives on the current standpoint of corneal xenotransplantation in the fields of regenerative medicine.
Topics: Animals; Animals, Genetically Modified; Cornea; Corneal Transplantation; Gene Editing; Gene Regulatory Networks; Genetic Engineering; Graft Survival; Humans; Immunosuppression Therapy; Transplantation, Heterologous
PubMed: 32755676
DOI: 10.1016/j.preteyeres.2020.100876 -
Einstein (Sao Paulo, Brazil) 2015Heart transplantation is currently the definitive gold standard surgical approach in the treatment of refractory heart failure. However, the shortage of donors limits... (Review)
Review
Heart transplantation is currently the definitive gold standard surgical approach in the treatment of refractory heart failure. However, the shortage of donors limits the achievement of a greater number of heart transplants, in which the use of mechanical circulatory support devices is increasing. With well-established indications and contraindications, as well as diagnosis and treatment of rejection through defined protocols of immunosuppression, the outcomes of heart transplantation are very favorable. Among early complications that can impact survival are primary graft failure, right ventricular dysfunction, rejection, and infections, whereas late complications include cardiac allograft vasculopathy and neoplasms. Despite the difficulties for heart transplantation, in particular, the shortage of donors and high mortality while on the waiting list, in Brazil, there is a great potential for both increasing effective donors and using circulatory assist devices, which can positively impact the number and outcomes of heart transplants.
Topics: Brazil; Chagas Cardiomyopathy; Graft Rejection; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Immunosuppression Therapy; Neoplasms; Opportunistic Infections; Postoperative Complications; Primary Graft Dysfunction; Tissue Donors
PubMed: 26154552
DOI: 10.1590/S1679-45082015RW3154 -
Pathologica Jun 2021Autoimmune hepatitis (AIH) is a relatively rare non-resolving chronic liver disease, which mainly affects women. It is characterized by hypergammaglobulinemia,... (Review)
Review
Autoimmune hepatitis (AIH) is a relatively rare non-resolving chronic liver disease, which mainly affects women. It is characterized by hypergammaglobulinemia, circulating autoantibodies, interface hepatitis on liver histology and a favourable response to immunosuppression. The putative mechanism for the development of autoimmune hepatitis is thought to be the interaction between genetic predisposition, environmental triggers and failure of the native immune system. AIH still remains a major diagnostic and therapeutic challenge, mainly because it is a very heterogeneous disease. Prompt and timely diagnosis is crucial since, if left untreated, AIH has a high mortality rate. Histological demonstration of hepatitis is required for the diagnosis of AIH and, therefore, liver biopsy is mandatory in the initial diagnostic work-up, before treatment. In this review, we summarize the histological features of AIH with the main aim of highlighting the most important clinical-pathological hallmarks useful in the routine diagnostic practice.
Topics: Autoantibodies; Female; Hepatitis, Autoimmune; Humans; Immunosuppression Therapy
PubMed: 34294936
DOI: 10.32074/1591-951X-241 -
Journal of Nephrology Apr 2021A large number of neurological disorders can affect renal transplant recipients, potentially leading to disabling or life-threatening complications. Prevention, early... (Review)
Review
A large number of neurological disorders can affect renal transplant recipients, potentially leading to disabling or life-threatening complications. Prevention, early diagnosis and appropriate management of these conditions are critical to avoid irreversible lesions. A pivotal role in the pathogenesis of common post-transplant neurological disorders is played by immunosuppressive therapy. The most frequently administered regimen consists of triple immunosuppression, which comprises a calcineurin inhibitor (CNI), a purine synthesis inhibitor and glucocorticoids. Some of these immunosuppressive drugs may lead to neurological signs and symptoms through direct neurotoxic effects, and all of them may be responsible for the development of tumors or opportunistic infections. In this review, after a brief summary of neurotoxic pathogenetic mechanisms encompassing recent advances in the field, we focus on the clinical presentation of more common and severe immunosuppression-related neurological complications, classifying them by characteristics of urgency and anatomic site. Our goal is to provide a general framework that addresses such clinical issues with a multidisciplinary approach, as these conditions require.
Topics: Calcineurin Inhibitors; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Nervous System Diseases
PubMed: 33481222
DOI: 10.1007/s40620-020-00956-1 -
Current Opinion in Lipidology Oct 2021This study reviews the mechanisms of HDL cholesterol immunomodulation in the context of the mechanisms of chronic inflammation and immunosuppression causing persistent... (Review)
Review
PURPOSE OF REVIEW
This study reviews the mechanisms of HDL cholesterol immunomodulation in the context of the mechanisms of chronic inflammation and immunosuppression causing persistent inflammation, immunosuppression and catabolism syndrome (PICS) and describes potential therapies and gaps in current research.
RECENT FINDINGS
Low HDL cholesterol is predictive of acute sepsis severity and outcome. Recent research has indicated apolipoprotein is a prognostic indicator of long-term outcomes. The pathobiologic mechanisms of PICS have been elucidated in the past several years. Recent research of the interaction of HDL pathways in related chronic inflammatory diseases may provide insights into further mechanisms and therapeutic targets.
SUMMARY
HDL significantly influences innate and adaptive immune pathways relating to chronic disease and inflammation. Further research is needed to better characterize these interactions in the setting of PICS.
Topics: Critical Illness; Humans; Immune Tolerance; Immunosuppression Therapy; Inflammation; Syndrome
PubMed: 34374677
DOI: 10.1097/MOL.0000000000000782 -
Kidney360 Dec 2022
Topics: Immunosuppression Therapy; Immunosuppressive Agents
PubMed: 36591358
DOI: 10.34067/KID.0005652022 -
The Veterinary Quarterly Dec 2023Certain pathogens, due to their adverse effects on the immune reaction, aggravate the course of concomitant heterologous infections. Here we summarize mechanisms by... (Review)
Review
Certain pathogens, due to their adverse effects on the immune reaction, aggravate the course of concomitant heterologous infections. Here we summarize mechanisms by which circoviruses, including the most studied porcine circovirus 2, and other mammalian and avian circoviruses, trigger their own replication and confound the hosts' immune response. At different stages of infection, from latent state to disease induction, these viruses markedly influence the cellular signaling pathways. Circoviruses have been found to interfere with interferon and proinflammatory cytokine producing and responsive pathways. Apoptotic processes, altered cellular transport and constraint of the mitotic phase all support the viral replication. The cytokine imbalance and lymphocyte depletion, thus the impaired immunity, favors invasion of super- or co-infecting agents, which in concert with circoviruses induce illnesses with increased severity. The information summarized in this review point out the diversity of host and viral factors involved in the mechanisms of disease progression during circovirus infections.
Topics: Swine; Animals; Circovirus; Circoviridae Infections; Virus Replication; Immunosuppression Therapy; Cytokines; Swine Diseases; Mammals
PubMed: 37431709
DOI: 10.1080/01652176.2023.2234430 -
Journal of Postgraduate Medicine 2021
Topics: COVID-19; Cytomegalovirus; Cytomegalovirus Infections; Humans; Immunization, Passive; Immunosuppression Therapy; Leukopenia; SARS-CoV-2; COVID-19 Serotherapy
PubMed: 33942769
DOI: 10.4103/jpgm.JPGM_55_21 -
Advanced Drug Delivery Reviews Sep 2023The rising incidence and persistent thrombosis in multiple cancers including those that are immunosuppressive highlight the need for understanding the tumor coagulome... (Review)
Review
The rising incidence and persistent thrombosis in multiple cancers including those that are immunosuppressive highlight the need for understanding the tumor coagulome system and its role beyond hemostatic complications. Immunotherapy has shown significant benefits in solid organ tumors but has been disappointing in the treatment of hypercoagulable cancers, such as glioblastoma and pancreatic ductal adenocarcinomas. Thus, targeting thrombosis to prevent immunosuppression seems a clinically viable approach in cancer treatment. Hypercoagulable tumors often develop fibrin clots within the tumor microenvironment (TME) that dictates the biophysical characteristics of the tumor tissue. The application of systems biology and single-cell approaches highlight the potential role of coagulome or thrombocytosis in shaping the tumor immune microenvironment (TIME). In-depth knowledge of the tumor coagulome would provide unprecedented opportunities to better predict the hemostatic complications, explore how thrombotic stroma modulates tumor immunity, reexamine the significance of clinical biomarkers, and enable steering the stromal versus systemic immune response for boosting the effectiveness of immune checkpoint inhibitors in cancer treatment. We focus on the role of coagulation factors in priming a suppressive TIME and the huge potential of existing anticoagulant drugs in the clinical settings of cancer immunotherapy.
Topics: Humans; Tumor Microenvironment; Immunotherapy; Pancreatic Neoplasms; Immunosuppression Therapy; Carcinoma, Pancreatic Ductal
PubMed: 37517779
DOI: 10.1016/j.addr.2023.115027 -
Cellular & Molecular Immunology Apr 2019Vascularized composite allotransplants (VCAs) have unique properties because of diverse tissue components transplanted en mass as a single unit. In addition to surgery,... (Review)
Review
Vascularized composite allotransplants (VCAs) have unique properties because of diverse tissue components transplanted en mass as a single unit. In addition to surgery, this type of transplant also faces enormous immunological challenges that demand a detailed analysis of all aspects of alloimmune responses, organ preservation, and injury, as well as the immunogenicity of various tissues within the VCA grafts to further improve graft and patient outcomes. Moreover, the side effects of long-term immunosuppression for VCA patients need to be carefully balanced with the potential benefit of a non-life-saving procedure. In this review article, we provide a comprehensive update on limb and face transplantation, with a specific emphasis on the alloimmune responses to VCA, established and novel immunosuppressive treatments, and patient outcomes.
Topics: Adaptive Immunity; Graft Rejection; Graft Survival; Humans; Immune Tolerance; Immunity, Innate; Immunosuppression Therapy; Immunosuppressive Agents; Risk Factors; Skin; Skin Transplantation; Vascularized Composite Allotransplantation
PubMed: 30842628
DOI: 10.1038/s41423-019-0215-3