-
Polish Archives of Internal Medicine Feb 2022
Topics: COVID-19; Humans; Immunosuppression Therapy; Organ Transplantation; Pandemics; SARS-CoV-2
PubMed: 35226438
DOI: 10.20452/pamw.16212 -
Human Immunology May 2024Intestinal allografts are the most immunologically complex and carry the highest risk of rejection among solid organ transplantation, necessitating complex... (Review)
Review
Intestinal allografts are the most immunologically complex and carry the highest risk of rejection among solid organ transplantation, necessitating complex immunosuppressive management. We evaluated the latest information regarding induction immunosuppression, with an emphasis on established, novel, and emergent therapies. We also reviewed classic and novel induction immunosuppression strategies for highly sensitized recipients. Comparable progress has been made in intestinal transplantation clinical outcomes since the implementation of induction strategies. This review shows a clear diversity of induction protocols can be observed across different centers. The field of intestinal transplantation is still in its early stages, which is further complicated by the limited number of institutions capable of intestinal transplantation and their geographical variation, which further hinders the development of adequately powered studies in comparison to other organs. As the implementation of institution-specific induction protocols becomes more refined and results are disseminated, future research efforts should be directed towards the development of efficacious induction strategies.
Topics: Humans; Intestines; Graft Rejection; Immunosuppressive Agents; Immunosuppression Therapy; Organ Transplantation
PubMed: 38599892
DOI: 10.1016/j.humimm.2024.110800 -
Frontiers in Bioscience (Elite Edition) Jan 2013Lung transplantation is a life saving treatment for end stage pulmonary diseases. The development and refinement of this therapy required the utilization of various... (Review)
Review
Lung transplantation is a life saving treatment for end stage pulmonary diseases. The development and refinement of this therapy required the utilization of various animal models, without which this procedure would not have become a clinical reality. Canine models were critical in the initial breakthroughs in surgical technique and immunosuppressive regimens, which directly led to the first successful human lung transplantation. Orthotopic lung transplant models in the rat provided a platform for more detailed investigation of immune responses to pulmonary grafts. Investigation of chronic rejection of lungs has significantly been advanced through the use of mouse tracheal transplant experiments. And finally, the advent of orthotopic, vascularized lung transplantation in the mouse opened the door to the use of genetic and molecular tools that are necessary for the rigorous mechanistic study of alloimmune and non-alloimmune factors contributing to lung graft failure. Taken together, animal models will continue to be a cornerstone in the advancement of clinical success in lung transplantation.
Topics: Animals; Dogs; Immunosuppression Therapy; Lung Transplantation; Mice; Models, Animal; Rats; Swine; Trachea
PubMed: 23276988
DOI: 10.2741/e614 -
American Journal of Transplantation :... Jun 2009Rapid advances have been made in decreasing acute rejection rates and improving short-term graft survival in kidney transplant recipients. Whether these advances... (Review)
Review
Rapid advances have been made in decreasing acute rejection rates and improving short-term graft survival in kidney transplant recipients. Whether these advances ultimately will lead to a commensurate improvement in long-term survival is not yet known. In recent years, greater attention has been placed on defining the precise etiology of graft loss, determining how far and with what agents we can minimize immunosuppression, and delineating the nature of both T-cell-mediated as well as antibody-mediated rejection. In addition, with the growing disparity of available organs and patients in need of a transplant, greater attention has been placed on optimizing allocation. In this minireview, we will focus on developments over the last couple of years, paying particular attention to insights, studies and observations that may attempt to elucidate some of these open questions.
Topics: Cyclosporine; Graft Rejection; Graft Survival; Humans; Immunosuppression Therapy; Kidney Transplantation; Mycophenolic Acid; Tissue and Organ Procurement
PubMed: 19459815
DOI: 10.1111/j.1600-6143.2009.02639.x -
Journal of the American Society of... Jul 2018
Topics: Calcineurin Inhibitors; Everolimus; Immunosuppression Therapy; Kidney Transplantation; Tacrolimus
PubMed: 29884733
DOI: 10.1681/ASN.2018050491 -
Gastroenterology Jan 1997
Topics: Animals; Dogs; History, 20th Century; Humans; Immunosuppression Therapy; Liver Transplantation; Transplantation Immunology; United States
PubMed: 8978371
DOI: 10.1016/s0016-5085(97)70246-4 -
BioMed Research International 2022To analyze the diagnosis and treatment of patients with concomitant malignant tumors after organ transplantation by compiling data from organ transplantation patients. (Review)
Review
OBJECTIVE
To analyze the diagnosis and treatment of patients with concomitant malignant tumors after organ transplantation by compiling data from organ transplantation patients.
METHODS
By searching CNKI and PubMed databases, we made a systematic analysis of the studies of postorgan transplantation complicating malignant tumors in the last decade.
RESULTS
There were 10 articles on malignant tumors after renal transplantation, 8 articles on liver transplantation, 2 articles on heart transplantation, and 1 article on lung transplantation. The incidence of malignant tumors complicating renal transplantation is 10.4% in Europe, with skin cancer and Kaposi's sarcoma being common; the incidence in the United States is 3.4%, with PTLD having the highest incidence; the incidence of malignant tumors is relatively lowest in Asia, with gastrointestinal malignancies being the main ones. The mean time to complication of malignancy after renal transplantation is 3.83 years. The incidence of concurrent malignancies after liver transplantation is 8.8% in Europe, where skin cancer and Kaposi's sarcoma are common; 5.6% in Asia, where gastrointestinal tract tumors are prevalent; and 4.5% in the United States, where gastrointestinal tract tumors, PTLD, and hematologic diseases are predominant. The mean time to complication of malignancy after liver transplantation is 4.79 years. The incidence of malignancy after heart transplantation is 6.8-10.7%. The incidence of malignancy after lung transplantation is about 10.1%. Minimization of immunosuppression or modification of immunosuppression regimens may be a key component of cancer prevention. mTOR inhibitors and phenolate (MMF) reduce the incidence of de novo malignancies in patients after solid organ transplantation. Surgical treatment improves survival in patients with early malignancies. The use of external beam radiation therapy in the treatment of hepatocellular carcinoma is limited due to the risk of radiation liver disease.
CONCLUSIONS
The risk of concomitant malignancy needs to be guarded for 5 years of immunosuppressive therapy after organ transplantation surgery. Adjusting the immunosuppressive treatment regimen is an effective way to reduce concurrent malignancies. Systemic chemotherapy or radiotherapy requires vigilance against the toxic effects of drug metabolism kinetics on the transplanted organ.
Topics: Antineoplastic Agents; Humans; Immunosuppression Therapy; Incidence; Neoplasms; Organ Transplantation; Radiotherapy
PubMed: 35224096
DOI: 10.1155/2022/5852451 -
Kidney International Nov 2015
Topics: Animals; Cell- and Tissue-Based Therapy; Graft Rejection; Humans; Immunosuppression Therapy; Kidney Transplantation; T-Lymphocytes, Regulatory
PubMed: 26579687
DOI: 10.1038/ki.2015.265 -
Life Sciences in Space Research Nov 2022Radiation-induced immune suppression poses significant health challenges for millions of patients undergoing cancer chemotherapy and radiotherapy treatment, and...
Radiation-induced immune suppression poses significant health challenges for millions of patients undergoing cancer chemotherapy and radiotherapy treatment, and astronauts and space tourists travelling to outer space. While a limited number of recombinant protein therapies, such a Sargramostim, are approved for accelerating hematologic recovery, the pronounced role of granulocyte-macrophage colony-stimulating factor (GM-CSF or CSF2) as a proinflammatory cytokine poses additional challenges in creating immune dysfunction towards pathogenic autoimmune diseases. Here we present an approach to high-throughput drug-discovery, target validation, and lead molecule identification using nucleic acid-based molecules. These Nanoligomer™ molecules are rationally designed using a bioinformatics and an artificial intelligence (AI)-based ranking method and synthesized as a single-modality combining 6-different design elements to up- or downregulate gene expression of target gene, resulting in elevated or diminished protein expression of intended target. This method additionally alters related gene network targets ultimately resulting in pathway modulation. This approach was used to perturb and identify the most effective upstream regulators and canonical pathways for therapeutic intervention to reverse radiation-induced immunosuppression. The lead Nanoligomer™ identified in a screen of human donor derived peripheral blood mononuclear cells (PBMCs) upregulated Erythropoietin (EPO) and showed the greatest reversal of radiation induced cytokine changes. It was further tested in vivo in a mouse radiation-model with low-dose (3 mg/kg) intraperitoneal administration and was shown to regulate gene expression of epo in lung tissue as well as counter immune suppression. These results point to the broader applicability of our approach towards drug-discovery, and potential for further investigation of our lead molecule as reversible gene therapy to treat adverse health outcomes induced by radiation exposure.
Topics: Mice; Animals; Humans; Leukocytes, Mononuclear; Artificial Intelligence; Recombinant Proteins; Cytokines; Immunosuppression Therapy; Granulocyte Colony-Stimulating Factor
PubMed: 36336358
DOI: 10.1016/j.lssr.2022.05.002 -
Transplantation Nov 2015Demographic changes are associated with a steady increase of older patients with end-stage organ failure in need for transplantation. As a result, the majority of... (Review)
Review
Demographic changes are associated with a steady increase of older patients with end-stage organ failure in need for transplantation. As a result, the majority of transplant recipients are currently older than 50 years, and organs from elderly donors are more frequently used. Nevertheless, the benefit of transplantation in older patients is well recognized, whereas the most frequent causes of death among older recipients are potentially linked to side effects of their immunosuppressants.Immunosenescence is a physiological part of aging linked to higher rates of diabetes, bacterial infections, and malignancies representing the major causes of death in older patients. These age-related changes impact older transplant candidates and may have significant implications for an age-adapted immunosuppression. For instance, immunosenescence is linked to lower rates of acute rejections in older recipients, whereas the engraftment of older organs has been associated with higher rejection rates. Moreover, new-onset diabetes mellitus after transplantation is more frequent in the elderly, potentially related to corticosteroids, calcineurin inhibitors, and mechanistic target of rapamycin inhibitors.This review presents current knowledge for an age-adapted immunosuppression based on both, experimental and clinical studies in and beyond transplantation. Recommendations of maintenance and induction therapy may help to improve graft function and to design future clinical trials in the elderly.
Topics: Age Factors; Aging; Animals; Comorbidity; Graft Rejection; Graft Survival; Humans; Immunocompromised Host; Immunosuppression Therapy; Immunosuppressive Agents; Middle Aged; Organ Transplantation; Patient Selection; Predictive Value of Tests; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 26244716
DOI: 10.1097/TP.0000000000000842