-
Nature Reviews. Immunology Mar 2020Cellular therapies using regulatory T (T) cells are currently undergoing clinical trials for the treatment of autoimmune diseases, transplant rejection and... (Review)
Review
Cellular therapies using regulatory T (T) cells are currently undergoing clinical trials for the treatment of autoimmune diseases, transplant rejection and graft-versus-host disease. In this Review, we discuss the biology of T cells and describe new efforts in T cell engineering to enhance specificity, stability, functional activity and delivery. Finally, we envision that the success of T cell therapy in autoimmunity and transplantation will encourage the clinical use of adoptive T cell therapy for non-immune diseases, such as neurological disorders and tissue repair.
Topics: Animals; Autoimmune Diseases; Cell- and Tissue-Based Therapy; Graft Rejection; Humans; Immunotherapy, Adoptive; T-Lymphocytes, Regulatory
PubMed: 31811270
DOI: 10.1038/s41577-019-0232-6 -
Kidney International Apr 2022Detection of mismatched human leukocyte antigens by adaptive immune cells is considered as the main cause of transplant rejection, leading to either T-cell mediated... (Review)
Review
Detection of mismatched human leukocyte antigens by adaptive immune cells is considered as the main cause of transplant rejection, leading to either T-cell mediated rejection or antibody-mediated rejection. This canonical view guided the successful development of immunosuppressive therapies and shaped the diagnostic Banff classification for kidney transplant rejection that is used in clinics worldwide. However, several observations have recently emerged that question this dichotomization between T-cell mediated rejection and antibody-mediated rejection, related to heterogeneity in the serology, histology, and prognosis of the rejection phenotypes. In parallel, novel insights were obtained concerning the dynamics of donor-specific anti-human leukocyte antigen antibodies, the immunogenicity of donor-recipient non-human leukocyte antigen mismatches, and the autoreactivity against self-antigens. Moreover, the potential of innate allorecognition was uncovered, as exemplified by natural killer cell-mediated microvascular inflammation through missing self, and by the emerging evidence on monocyte-driven allorecognition. In this review, we highlight the gaps in the current classification of rejection, provide an overview of the expanding insights into the mechanisms of allorecognition, and critically appraise how these could improve our understanding and clinical approach to kidney transplant rejection. We argue that consideration of the complex interplay of various allorecognition mechanisms can foster a more integrated view of kidney transplant rejection and can lead to improved risk stratification, targeted therapies, and better outcome after kidney transplantation.
Topics: Antibodies; Graft Rejection; HLA Antigens; Humans; Immunosuppression Therapy; Kidney Transplantation; Postoperative Complications; Tissue Donors
PubMed: 34915041
DOI: 10.1016/j.kint.2021.11.029 -
Frontiers in Immunology 2021Despite advances in post-transplant management, the long-term survival rate of kidney grafts and patients has not improved as approximately forty percent of transplants... (Review)
Review
Despite advances in post-transplant management, the long-term survival rate of kidney grafts and patients has not improved as approximately forty percent of transplants fails within ten years after transplantation. Both immunologic and non-immunologic factors contribute to late allograft loss. Chronic kidney transplant rejection (CKTR) is often clinically silent yet progressive allogeneic immune process that leads to cumulative graft injury, deterioration of graft function. Chronic active T cell mediated rejection (TCMR) and chronic active antibody-mediated rejection (ABMR) are classified as two principal subtypes of CKTR. While significant improvements have been made towards a better understanding of cellular and molecular mechanisms and diagnostic classifications of CKTR, lack of early detection, differential diagnosis and effective therapies continue to pose major challenges for long-term management. Recent development of high throughput cellular and molecular biotechnologies has allowed rapid development of new biomarkers associated with chronic renal injury, which not only provide insight into pathogenesis of chronic rejection but also allow for early detection. In parallel, several novel therapeutic strategies have emerged which may hold great promise for improvement of long-term graft and patient survival. With a brief overview of current understanding of pathogenesis, standard diagnosis and challenges in the context of CKTR, this mini-review aims to provide updates and insights into the latest development of promising novel biomarkers for diagnosis and novel therapeutic interventions to prevent and treat CKTR.
Topics: Antibodies; Biomarkers; Chronic Disease; Early Diagnosis; Graft Rejection; Humans; Kidney; Kidney Transplantation; T-Lymphocytes; Transplantation, Homologous
PubMed: 34093552
DOI: 10.3389/fimmu.2021.661643 -
Clinical Journal of the American... Jan 2018Donor-specific antibodies have become an established biomarker predicting antibody-mediated rejection. Antibody-mediated rejection is the leading cause of graft loss... (Review)
Review
Donor-specific antibodies have become an established biomarker predicting antibody-mediated rejection. Antibody-mediated rejection is the leading cause of graft loss after kidney transplant. There are several phenotypes of antibody-mediated rejection along post-transplant course that are determined by the timing and extent of humoral response and the various characteristics of donor-specific antibodies, such as antigen classes, specificity, antibody strength, IgG subclasses, and complement binding capacity. Preformed donor-specific antibodies in sensitized patients can trigger hyperacute rejection, accelerated acute rejection, and early acute antibody-mediated rejection. donor-specific antibodies are associated with late acute antibody-mediated rejection, chronic antibody-mediated rejection, and transplant glomerulopathy. The pathogeneses of antibody-mediated rejection include not only complement-dependent cytotoxicity, but also complement-independent pathways of antibody-mediated cellular cytotoxicity and direct endothelial activation and proliferation. The novel assay for complement binding capacity has improved our ability to predict antibody-mediated rejection phenotypes. C1q binding donor-specific antibodies are closely associated with acute antibody-mediated rejection, more severe graft injuries, and early graft failure, whereas C1q nonbinding donor-specific antibodies correlate with subclinical or chronic antibody-mediated rejection and late graft loss. IgG subclasses have various abilities to activate complement and recruit effector cells through the Fc receptor. Complement binding IgG3 donor-specific antibodies are frequently associated with acute antibody-mediated rejection and severe graft injury, whereas noncomplement binding IgG4 donor-specific antibodies are more correlated with subclinical or chronic antibody-mediated rejection and transplant glomerulopathy. Our in-depth knowledge of complex characteristics of donor-specific antibodies can stratify the patient's immunologic risk, can predict distinct phenotypes of antibody-mediated rejection, and hopefully, will guide our clinical practice to improve the transplant outcomes.
Topics: Animals; Antibody Specificity; Graft Rejection; Graft Survival; HLA Antigens; Histocompatibility; Humans; Immunosuppressive Agents; Isoantibodies; Kidney Transplantation; Risk Factors; Treatment Outcome
PubMed: 28446536
DOI: 10.2215/CJN.00700117 -
Nature Reviews. Drug Discovery Oct 2019Regulatory T cells (T cells) are a small subset of immune cells that are dedicated to curbing excessive immune activation and maintaining immune homeostasis.... (Review)
Review
Regulatory T cells (T cells) are a small subset of immune cells that are dedicated to curbing excessive immune activation and maintaining immune homeostasis. Accordingly, deficiencies in T cell development or function result in uncontrolled immune responses and tissue destruction and can lead to inflammatory disorders such as graft-versus-host disease, transplant rejection and autoimmune diseases. As T cells deploy more than a dozen molecular mechanisms to suppress immune responses, they have potential as multifaceted adaptable smart therapeutics for treating inflammatory disorders. Indeed, early-phase clinical trials of T cell therapy have shown feasibility, tolerability and potential efficacy in these disease settings. In the meantime, progress in the development of chimeric antigen receptors and in genome editing (including the application of CRISPR-Cas9) over the past two decades has facilitated the genetic optimization of primary T cell therapy for cancer. These technologies are now being used to enhance the specificity and functionality of T cells. In this Review, we describe the key advances and prospects in designing and implementing T cell-based therapy in autoimmunity and transplantation.
Topics: Animals; Autoimmune Diseases; Cell- and Tissue-Based Therapy; Graft Rejection; Humans; Neoplasms; T-Lymphocytes, Regulatory
PubMed: 31541224
DOI: 10.1038/s41573-019-0041-4 -
Clinical Journal of the American... Mar 2020Advances in immunosuppressive therapy have drastically improved acute rejection rates in kidney transplant recipients over the past five decades. Nevertheless, it should...
Advances in immunosuppressive therapy have drastically improved acute rejection rates in kidney transplant recipients over the past five decades. Nevertheless, it should remain high on any differential diagnosis of unexplained graft dysfunction because of the potential negative effect on graft longevity. Understanding the pre- and post-transplant risk factors for acute rejection can help estimate the probability of immunologic graft damage, and accurate identification of the type and severity of acute rejection will guide appropriate treatment. Tissue biopsy remains the gold standard for evaluating immunologic graft damage, and the histologic definition of acute rejection has evolved in recent years. Intravenous steroids and T cell depletion remain the standard therapy for T cell-mediated rejection and are effective in reversing most cases. Plasma exchange and intravenous Ig, with or without rituximab, are most commonly used for the treatment of antibody-mediated rejection and several newer agents have recently been investigated for severe cases. This review aims to provide the general nephrologist caring for transplant recipients with an approach to immunologic risk assessment and a summary of recent advances in the diagnosis and treatment of acute graft rejection.
Topics: Acute Disease; Algorithms; Clinical Decision-Making; Decision Support Techniques; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 32066593
DOI: 10.2215/CJN.11991019 -
JACC. Heart Failure Mar 2023Noninvasive heart transplant rejection surveillance using gene expression profiling (GEP) to monitor immune activation is widely used among heart transplant programs.... (Review)
Review
Noninvasive heart transplant rejection surveillance using gene expression profiling (GEP) to monitor immune activation is widely used among heart transplant programs. With the new development of donor-derived cell-free DNA (dd-cfDNA) assays, more programs are transitioning to a predominantly noninvasive rejection surveillance protocol with a reduced frequency of endomyocardial biopsies. As a result, many practical questions arise that potentially delay implementation of these valuable new tools. The purpose of this review is to provide practical guidance for clinicians transitioning toward a less invasive acute rejection monitoring protocol after heart transplantation, and to answer 10 common questions about the GEP and dd-cfDNA assays. Evidence supporting GEP and dd-cfDNA testing is reviewed, as well as guidance on test interpretation and future directions.
Topics: Humans; Graft Rejection; Heart Failure; Heart Transplantation; Postoperative Complications; Biopsy; Cell-Free Nucleic Acids; Tissue Donors
PubMed: 36682960
DOI: 10.1016/j.jchf.2022.11.002 -
Kidney International Apr 20222021 marks the 30th anniversary of the original development of the Banff Classification of Kidney Allograft Pathology, when in August 1991 a group of pathologists and... (Review)
Review
2021 marks the 30th anniversary of the original development of the Banff Classification of Kidney Allograft Pathology, when in August 1991 a group of pathologists and transplant clinicians led by Kim Solez and Lorraine Racusen met in Banff, Alberta, Canada, and established the first widely accepted criteria for the diagnosis of kidney transplant rejection and other lesions seen on kidney allograft biopsies. Since that time, Banff conferences have been held every 2 years at many sites around the world, resulting in several major revisions to the classification and expansion well beyond pure histopathology of kidney allografts to encompass other solid organ transplants, and with involvement of immunogeneticists, immunologists, other basic scientists, biostatisticians, and data scientists defining a very diverse and integrated Banff community. This approach with multidisciplinary international input, constantly incorporating new evidence from the scientific literature and from studies performed by Banff working groups while still maintaining the importance of a long-standing consensus process, has resulted in the Banff classification gaining overwhelming international acceptance as the main reference used for the scoring of kidney allograft biopsies in research studies, routine practice, and clinical trials. This review focuses on the major milestones in the development of the Banff classification of kidney allograft pathology and the evolution of the Banff process over the past 3 decades, with prospects for future advances and refinements.
Topics: Alberta; Allografts; Biopsy; Graft Rejection; Humans; Kidney; Kidney Transplantation; Transplantation, Homologous
PubMed: 34922989
DOI: 10.1016/j.kint.2021.11.028 -
Frontiers in Immunology 2022
Topics: Graft Rejection; Heart Transplantation
PubMed: 35812419
DOI: 10.3389/fimmu.2022.960800 -
Respirology (Carlton, Vic.) Jan 2013Lung transplantation has become an accepted therapeutic procedure for the treatment of end-stage pulmonary parenchymal and vascular disease. Despite improved survival... (Review)
Review
Lung transplantation has become an accepted therapeutic procedure for the treatment of end-stage pulmonary parenchymal and vascular disease. Despite improved survival rates over the decades, lung transplant recipients have lower survival rates than other solid organ transplant recipients. The morbidity and mortality following lung transplantation is largely due to infection- and rejection-related complications. This article will review the common infections that develop in the lung transplant recipient, including the general risk factors for infection in this population, and the most frequent bacterial, viral, fungal and other less frequent opportunistic infections. The epidemiology, diagnosis, prophylaxis, treatment and outcomes for the different microbial pathogens will be reviewed. The effects of infection on lung transplant rejection will also be discussed.
Topics: Bacterial Infections; Graft Rejection; Humans; Lung; Lung Diseases; Lung Transplantation; Mycoses; Postoperative Complications; Risk Factors; Virus Diseases
PubMed: 22591266
DOI: 10.1111/j.1440-1843.2012.02196.x