ABSTRACT
Kidney transplantation is the optimal treatment for patients with end-stage renal disease, whereas long-term survival of renal allografts remains a challenging issue. Renal ischemia-reperfusion injury (IRI) and rejection of renal allografts are considered as important influencing factors of long-term survival of renal allografts, which are regulated by innate and adaptive immune cells. Macrophages are one type of innate immune cells that could assist initiating adaptive immunity and are divided into M1, M2 and regulatory macrophages. Previous studies have revealed that M1 macrophages may aggravate renal IRI and acute T cell-mediated rejection (TCMR). However, M2 macrophages may mitigate renal IRI and acute TCMR, whereas it is positively correlated with antibody-mediated rejection (AMR). Regulatory macrophages are a special subgroup of macrophages, which may induce immune tolerance in organ transplantation and have promising clinical application prospects and basic scientific research value. In this article, the relationship among macrophage typing, macrophages and renal IRI, rejection of renal allografts, regulatory macrophages and immune tolerance was reviewed, and the potential mechanism was analyzed, aiming to induce changes in macrophage subtypes or eliminate specific subtypes of macrophages, thereby improving clinical prognosis of the recipients and long-term survival of renal allografts.
ABSTRACT
Pancreas transplantation and pancreas-kidney transplantation are the optimal treatment for renal failure caused by type 1 diabetes mellitus, partial type 2 diabetes mellitus and their complications. Pancreas transplantation mainly includes simultaneous pancreas-kidney transplantation (SPK), pancreas transplantation after kidney transplantation (PAK) and pancreas transplantation alone (PTA). Among all types of pancreas transplantation, biopsy of pancreas allograft remains the best method for definitively diagnosing rejection and differentiate it from other complications. In this article, biopsy methods of pancreas allograft and related research progress, diagnostic criteria and research progress on rejection of pancreas allograft biopsy, and main complications and pathological manifestations of pancreas allograft were illustrated, aiming to provide reference for guiding the clinical diagnosis of the above mentioned complications and ensuring the long-term survival of pancreas allografts and recipients.
ABSTRACT
In recent years, the quantity of lung transplantation has been gradually increased in China along with the accumulation of surgical techniques and postoperative management experience of lung transplantation. Multiple lung allograft complications may occur after lung transplantation, mainly including primary graft dysfunction (PGD) caused by ischemia-reperfusion injury (IRI) of the lung allograft, acute and chronic rejection, opportunistic infection or lymphoproliferative disorder of lymphoid tissues induced by the decrease of host immunity due to postoperative use of immunosuppressants, etc. The diagnosis of complications after lung transplantation mainly relies on biopsy of the lung allograft. In this article, the brief history of lung allograft pathology, main approaches and pathological processing techniques of lung allograft biopsy, major complications after lung transplantation and pathological diagnostic criteria were elucidated, aiming to provide reference for targeted management of these complications in clinical practice.
ABSTRACT
Early diagnosis and treatment of rejection after kidney transplantation play a critical role in alleviating allograft injury. Detection of donor-derived cell-free DNA (dd-cfDNA) could be performed based on the next-generation sequencing and other techniques. The content of DNA fragments derived from necrotic and apoptotic donor kidney tissues in circulating body fluids could be determined by concentration and absolute quantitative methods, which has application potential in monitoring allograft injury in clinical practice. Compared with traditional serum creatinine and other indicators, dd-cfDNA detection may monitor allograft injury from several weeks to months in advance, providing a "time window" for clinical treatment and delaying graft failure. Along with deepening research of dd-cfDNA in recent years, dd-cfDNA has captivated widespread attention due to its non-invasiveness, high sensitivity and real-time evaluation of therapeutic effect. In this article, current study evidence and conclusions related to multidimensional application of dd-cfDNA detection in diagnosis and treatment of kidney transplantation were reviewed, and the future research and clinical application direction of dd-cfDNA were discussed, aiming to provide reference for widespread application of dd-cfDNA detection in clinical practice in China.
ABSTRACT
Composite tissue allotransplantation (CTA) is a novel transplantation discipline to treat functional tissue or limb defects. Since a majority of CTA grafts were vascularized grafts, it is also known as vascularized composite allotransplantation (VCA). The grafts of CTA/VCA consist of two or more types of allogeneic skin, subcutaneous tissue, bone, muscle, nerve and vessel, etc. Most of CTA/VCA grafts contain skin tissues, which possess the highest antigenicity. Acute rejection after transplantation is the primary obstacle leading to CTA/VCA graft failure and primary graft dysfunction. Hence, histopathological characteristics of skin rejection in CTA/VCA grafts have become the primary hotspot. In this article, pathological features of CTA/VCA rejection, Banff classification in 2007 and related research progress were reviewed, aiming to provide reference for the diagnosis and treatment of rejection and other complications of CTA/VCA.
ABSTRACT
With the improvement of surgical technique of heart transplantation and clinical application of potent immunosuppressant, the quantity of heart transplantation and the survival time of heart allograft have been significantly improved. However, a series of complications, such as right ventricular failure, ischemia-reperfusion injury, acute rejection, "Quilty lesion", infection and chronic rejection characterized by transplant coronary artery disease (TCAD) may still occur at different stages after heart transplantation. The application of endomyocardial biopsy (EMB) makes it possible to observe and understand the pathological features of multiple complications of heart allograft including rejection, which has become the most accurate diagnostic tool for postoperative complications. In this article, the brief history of heart allograft pathology, main postoperative complications and pathological diagnostic criteria, and cutting edge research progress on diagnostic criteria of rejection were illustrated, aiming to bring clinical benefits to more recipients undergoing heart transplantation.
ABSTRACT
Kidney transplantation is the most efficacious treatment for end-stage renal failure. Although the shortterm survival and functional recovery of the kidney graft have been significantly improved, the long-term survival of the kidney graft remains to be enhanced. Antibody-mediated rejection (AMR) and T cell-mediated rejection (TCMR) caused by immune factors are still the most critical causes of kidney graft failure. In this article, the immune risk assessment and monitoring of kidney transplant recipients during the awaiting period, before and after kidney transplantation were reviewed. Through the evaluation of preexisting human leukocyte antigen (HLA) antibodies and non-HLA antibodies, HLA matching, lymphocytotoxicity cross-matching and immune memory cells in the recipients before kidney transplantation, programmed biopsy of the kidney graft of the recipients after kidney transplantation and monitoring of HLA antibodies, non-HLA antibodies and donor-derived cell-free DNA (dd-cfDNA), individualized immunosuppressive treatment and monitoring regimes could be established, and the incidence of rejection could be prevented, timely detected and diagnosed. According to the immune monitoring results, ineffective treatment or over-treatment could be avoided, thereby improving the long-term survival of kidney graft.
ABSTRACT
The pathology of liver allograft biopsy is not only essential for the evaluation of liver donor, but also for the diagnosis and differential diagnosis of posttransplantation complications. With the development of liver transplantation in clinical practice, relevant studies of the pathological diagnosis of liver allograft complications have been deepened. Banff classification on liver allograft pathology have been gradually established within the international community. In China, pathological studies related to liver allograft pathology have been steadily carried out, and the pathological diagnostic basis of liver allograft pathology suitable for the clinical practice of liver transplantation in China has been gradually formed. This article reviews the history of Banff liver allograft pathology and major pathological lesions of liver allograft complications, aiming to provide reference for implementing pathological diagnosis of liver allograft pathology in China, assisting clinical diagnosis and targeted treatment of complications after liver transplantation, and further improving the survival of liver allograft and recipients.
ABSTRACT
Antibody-mediated rejection (AMR), also known as humoral rejection, is an immune injury caused by rejection involved with multiple humoral immune effectors, such as antibodies and complements, etc. AMR plays a pivotal role in hyperacute, acute and chronic rejection. In this article, the basic definition of AMR, the research progress and major achievements on AMR pathology according to Banff classification on allograft pathology (Banff classification), and main pathological characteristics of AMR in renal allograft were reviewed, aiming to provide reference for accurate diagnosis and timely treatment of AMR, and guarantee the long-term survival of renal graft and recipients.
ABSTRACT
T cell-mediated rejection (TCMR) is one of the main mechanisms of rejection in organ transplantation, which is also the most common type of acute rejection.Based on Banff classification on allograft pathology (Banff classification) in 2019, TCMR can be divided into acute TCMR (aTCMR) and chronic active TCMR (caTCMR) according to the characteristics of immune lesions.In this article, the basic definition of TCMR, the research progress on TCMR pathology according to Banff classification for renal allograft, and the basic pathological changes and diagnostic grading of TCMR were reviewed, aiming to provide evidence for early identification, diagnosis and treatment of TCMR and prevent the progression of TCMR into caTCMR, thereby guarantying the long-term survival of both the renal allograft and recipient.
ABSTRACT
BK polyomavirus-associated nephropathy (BKPyVAN) is a common cause of allograft failure. However, differentiation between BKPyVAN and type I T cell-mediated rejection (TCMR) is challenging when simian virus 40 (SV40) staining is negative, because of the similarities in histopathology. This study investigated whether donor-derived cell-free DNA (ddcfDNA) can be used to differentiate BKPyVAN. Target region capture sequencing was applied to detect the ddcfDNAs of 12 recipients with stable graft function, 22 with type I TCMR, 21 with proven BKPyVAN, and 5 with possible PyVAN. We found that urinary ddcfDNA levels were upregulated in recipients with graft injury, whereas plasma ddcfDNA levels were comparable for all groups. The median urinary concentrations and fractions of ddcfDNA in proven BKPyVAN recipients were significantly higher than those in type I TCMR recipients (10.4 vs. 6.1 ng/mL,