ABSTRACT
Objective:To evaluate the effect of parental liver donation on early acute cellular rejection(ACR)after liver transplantation(LT)in children aged under one year.Methods:From January 2018 to January 2021, retrospective review is conducted for clinical data of living donor LT recipients and donors aged under 1 year at Tianjin First Central Hospital.Donor livers are assigned into two groups of paternal donor liver(156 cases)and maternal donor liver(206 cases)according to the source of donor liver, Clinical characteristics and postoperative ACR occurrence of two groups are analyzed.Results:The rates of ACR during early postoperative period is 14.9%(54/362), 20.5%(32/156)in paternal liver donor group and 10.7%(22/206)in maternal liver donor group.There is statistically significant difference(λ 2=6.763, P=0.009).In analysis of gender matching of donor recipients, the rates of ACR is 22.6% in paternal donor group and 10.3% in maternal donor group.There is statistically significant difference(λ 2=5.411, P=0.020).Median time of initial postoperative ACR is 13.00(8.25~20.25)day in paternal liver donor group and 17.00(9.00~28.25)day in maternal donor group.The difference is not statistically significant( P>0.05). ACR is mostly mild-to-moderate in two groups . Conclusions:In living donor LT for children aged under 1 year, the rates of early ACR is lower for maternal donor than that for paternal donor, especially in female 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
Rejection after lung transplantation, including acute rejection (AR) and chronic rejection manifested with chronic lung allograft dysfunction (CLAD), is the main factor affecting the long-term survival of allografts. Exosome, a type of extracellular nanovesicle for intercellular communication among eukaryotic cells, could carry complex biological information and participate in various physiological and pathological processes. Exosome has become a critical immune medium in rejection, regulates the incidence and development of rejection through multiple pathways, and also plays a key role in the monitoring and management of rejection. In this article, the type of rejection after lung transplantation, the mechanism underlying the role of exosome in regulating rejection, exosome acting as biomarkers and the application in rejection treatment were reviewed, aiming to provide a novel direction for comprehensive diagnosis and treatment of rejection following lung transplantation.
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
Acute cellular rejection (ACR) is a common complication after lung transplantation, which is mainly caused by the immune response of T lymphocytes recognizing the major histocompatibility complex on the cellular surface of grafts. It is currently considered as the main pattern of acute rejection. ACR is not only a direct cause of death of recipients, but also a high-risk factor for chronic rejection after lung transplantation. Nevertheless, it is a challenging task to deliver the diagnosis and treatment of ACR following lung transplantation. In this article, new progresses on the risk factors, pathogenesis, diagnosis and treatment of ACR in lung transplant recipients were summarized, aiming to improve the diagnostic and treatment efficiency of ACR and prolong the survival of recipients.
ABSTRACT
Acute cellular rejection (ACR) remains a major concern after liver transplantation. Predicting and monitoring acute rejection by non-invasive methods are very important for guiding the use of immunosuppressive drugs. Many studies have shown that exosomes and their contents are potential biomarkers for various liver diseases. Here, we identify and validate the role of exosomes and galectin-9 in ACR after liver transplantation. Exosomes were isolated from three sets of paired patients, with and without ACR, and the proteins within the exosomes were isolated and identified. Candidate proteins were then validated using a tissue microarray containing resected liver samples from 73 ACR and 63 non-rejection patients. Finally, protein expression and clinical manifestations were included in Kaplan-Meier survival and Cox regression analyses. Circulating exosomes were isolated from ACR and non-rejection patients and characterized using transmission electron microscopy and western blotting for CD63/CD81. Western blotting experiments revealed higher levels of galectin-9 protein in circulating exosomes from ACR recipients. Immunohistochemical analysis of the tissue microarray showed that the expression of galectin-9 in resected liver was significantly higher in the ACR group than in the non-rejection group (P<0.05). Higher levels of galectin-9 expression in resected livers were associated with poorer prognosis (P<0.05). Exosome-derived galectin-9 may be a novel predictor of rejection and prognosis after liver transplantation.
ABSTRACT
BACKGROUND: The aim of this study was to investigate the clinical significance of Quilty lesions in endomyocardial biopsies (EMBs) of cardiac transplantation patients. METHODS: A total of 1190 EMBs from 117 cardiac transplantation patients were evaluated histologically for Quilty lesions, acute cellular rejection, and antibody-mediated rejection. Cardiac allograft vasculopathy was diagnosed by computed tomography coronary angiography. Clinical information, including the patients’ survival was retrieved by a review of medical records. RESULTS: Eighty-eight patients (75.2%) were diagnosed with Quilty lesions, which were significantly associated with acute cellular rejection, but not with acute cellular rejection ≥ 2R or antibody-mediated rejection. In patient sdiagnosed with both Quilty lesions and acute cellular rejection, the time-to-onset of Quilty lesions from transplantation was longer than that of acute cellular rejections. We found a significant association between Quilty lesions and cardiac allograft vasculopathy. No significant relationship was found between Quilty lesions and the patients’ survival. CONCLUSIONS: Quilty lesion may be an indicator of previous acute cellular rejection rather than a predictor for future acute cellular rejection.
Subject(s)
Humans , Allografts , Biopsy , Coronary Angiography , Heart Transplantation , Heart , Medical RecordsABSTRACT
Acute cellular rejection (ACR) remains a major concern after liver transplantation. Predicting and monitoring acute rejection by non-invasive methods are very important for guiding the use of immunosuppressive drugs. Many studies have shown that exosomes and their contents are potential biomarkers for various liver diseases. Here, we identify and validate the role of exosomes and galectin-9 in ACR after liver transplantation. Exosomes were isolated from three sets of paired patients, with and without ACR, and the proteins within the exosomes were isolated and identified. Candidate proteins were then validated using a tissue microarray containing resected liver samples from 73 ACR and 63 non-rejection patients. Finally, protein expression and clinical manifestations were included in Kaplan-Meier survival and Cox regression analyses. Circulating exosomes were isolated from ACR and non-rejection patients and characterized using transmission electron microscopy and western blotting for CD63/CD81. Western blotting experiments revealed higher levels of galectin-9 protein in circulating exosomes from ACR recipients. Immunohistochemical analysis of the tissue microarray showed that the expression of galectin-9 in resected liver was significantly higher in the ACR group than in the non-rejection group (P<0.05). Higher levels of galectin-9 expression in resected livers were associated with poorer prognosis (P<0.05). Exosome-derived galectin-9 may be a novel predictor of rejection and prognosis after liver transplantation.
ABSTRACT
Background: Kidney transplantation is the preferred mode of renal replacement therapy for the endstage renal disease, with dramatic improvements in patient and graft survival over the last 50 years. In the modern era of immunosuppression, 1-year patient survival is close to 98%, and 1-year allograft survival rates have improved to 90% for deceased donor kidney transplants and 95 % for living donor kidney transplants with some inter-center variability. The aim of the study: To elucidate the etiology of graft dysfunction among renal transplant recipients. Materials and methods: A retrospective study was conducted among 155 patients who underwent both cadavers and live donor transplant from October 2009 to March 2011 at a tertiary care center in Chennai, South India. All the transplant recipients were regularly followed with serum urea and creatinine, urine routine, calcineurin inhibitor drug levels in the serum, USG Abdomen, urine culture depending on the graft status. Graft dysfunction defined by a rise in the creatinine more than 25% or 0.3 to 0.5 mg per dl from the baseline. Those who developed graft dysfunction were presented for graft biopsy and managed based on the report accordingly. S. Thirumavalavan, Krishna Kumar, S. A. K. Noor Mohamed, R Vijaya Kumar. Etiology of graft dysfunction in renal transplant recipients. IAIM, 2019; 6(3): 313-318. Page 314 Results: Among the 155 transplant recipient patients, 66 (44%) patients developed graft dysfunction and underwent renal biopsy. The graft dysfunction was due to chronic allograft dysfunction (interstitial fibrosis and tubular atrophy) in 24 (15.4%) patients, acute cellular rejection in 13 (8.4%) patients, acute antibody-mediated rejection in 2 (1.3%) patients, acute tubular necrosis in 9 (5.8%) patients, calcineurin toxicity in 6 (3.9%) patients, thrombotic microangiopathy in 6 (3.9%) patients, IgA nephropathy in 3 (1.9%) patients and transplant renal artery stenosis in 1(0.6%) patient. Conclusion: Among the various causes, acute cellular, acute antibody rejection and chronic allograft nephropathy holds nearly 25% of the incidence of graft dysfunction. It indicates appropriate immunological evaluation, appropriate immunosuppression, use of induction agents in high-risk patients and protocol renal biopsy to identify early rejection in high-risk patient and appropriate early intervention is important to improve long-term term graft and patient survival.
ABSTRACT
Objective To investigate evaluation role of IP-10 level in urine of kidney transplant recipients when using rabbit anti-human T-lymphocyte immunoglobulin to treat acute cellular rejection.Methods A total of 40 patients who underwent renal transplantation and had been diagnosed as acute cellular rejection according to the results of histopathological examination were randomly divided them into IP-10 group (n =20) and serum creatinine group (Scr group,n =20).Urinary IP-10 and Scr levels were measured in time and patients then were treated with ATG,of which the doses and duration were adjusted according to IP-10 or Scr levels.We compared the total and daily ATG dosages,ATG administration period,side effects of ATG such as incidence of severe platelet and neutropenia,acute rejection during first 3 months and infection rates during first 1 year.Result The number of ATG duration is 5.35 ± 1.93 for IP-10 group versus 6.70 ± 1.75 for Scr group.We used a daily dose of 2.50 ± 0.57 mg/(kg·d) for IP-10 group and 2.77 ± 0.74 mg/(kg· d) for Scr group,a total dose of 13.40 ± 6.59 mg/kg for IP-10 group and 18.25 ± 7.35 mg/kg for Scr group.There was significance between the two group in above three outcomes (P ＜ 0.05).There was no significance in incidences of severe thrombocytopenia and neutropenia,incidences of acute rejection during first 3 months,incidences of infection during first 1 year between the two group (P ＞ 0.05).Conclusion Urine IP-10 test is effective and reliable indicators which can guide ATG usage in patients with acute rejection and reduce the ATG cost.
ABSTRACT
La biopsia hepática de los aloinjertos sigue siendo considerada el estándar de oro y juega un papel importante e integral en la interpretación y explicación de los cambios que puedan ocurrir en respuesta a alteraciones en las pruebas de la función o bioquímica hepática, anomalías funcionales o alteración en las imágenes diagnósticas, las cuales pueden, o no, ir acompañadas de síntomas. También es útil en el seguimiento o biopsias por protocolo (1-3). La evaluación de biopsias, después del trasplante, puede ser difícil debido a que es muy amplio el espectro de las complicaciones que pueden presentarse en el período postrasplante; más aún, cuando muchas de ellas necesitan un diagnóstico y tratamiento inmediato. La patología más frecuente es el rechazo agudo. Sin embargo, también pueden observarse cambios de perfusión/reperfusión, alteraciones funcionales, recidiva de enfermedad de base, lesión de la vía biliar, lesiones vasculares, infecciones oportunistas, patologías de novo, como la hepatitis autoinmune, hepatitis crónica idiopática postrasplante, toxicidad farmacológica o tumores, entre otras patologías (4). En este artículo relacionado con la patología del trasplante hepático se tratarán las patologías más frecuentes, no quirúrgicas, en el período postrasplante temprano, con un enfoque histopatológico dirigido a las dificultades y controversias para una adecuada correlación clínico-patológica.
Biopsies of liver allografts are still considered to be the gold standard. They play an important and integral role in the interpretation and explanation of changes that may occur in response to alterations in function tests, in the interpretation and explanation of liver biochemistry, in the interpretation and explanation of functional abnormalities, and in the interpretation and explanation of diagnostic images (whether or not accompanied by symptoms). Biopsies are also useful for monitoring and are often part of the protocol (1-3). The evaluation of biopsy samples after transplantation can be difficult especially because of the very broad spectrum of complications that may arise in the post-transplant period. Many of them require immediate diagnosis and treatment despite this difficulty. Although the most common condition is acute rejection, many other conditions and disorders can be observed. They include perfusion/reperfusion alterations, functional impairment, recurrence of underlying diseases, injury to the bile duct, vascular lesions, opportunistic infections, de novo pathologies such as autoimmune hepatitis, post-transplant idiopathic chronic hepatitis, drug toxicity, and tumors (4). This is the second article about the pathology of liver transplantation. It discusses the most common pathologies in the early post-transplant period and provides a histopathological approach towards difficulties and controversies for adequate clinicopathological correlation.
Subject(s)
Humans , Male , Female , Biopsy , Endothelium , Graft Rejection , Liver Transplantation , Primary Graft Dysfunction , Reperfusion InjuryABSTRACT
Objective To investigate the protein markers that specifically expressed in patients with acute rejection (ACR) after liver transplantation, and to explore preliminarily the mechanisms. Methods Serum samples from three patients with pathologically confirmed ACR after liver transplantation in Tianjin First Central Hospital were collected as ACR group. Three serum samples from patients with normal liver function indicators after liver transplantation were collected as No-ACR group. And six serum samples from healthy examination were mixed with equal amount as healthy control group. Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) was employed to separate, screen and identify the differentially expressed proteins between three groups. KEGG and STRING software were applied to deeply analyze the data of three groups. Results A total of 88 differentially expressed proteins were found between ACR group and healthy control group. There were 39 differentially expressed proteins between No-ACR group and healthy control group. Ten differentially expressed proteins were acquired between ACR group and No-ACR group. Comparing 88 and 10 differentially expressed proteins, 9 proteins were the same. Among 88 differentially expressed proteins, 30 of them showed a direct interaction, and can be positioned in 13 signaling pathways based on KEGG and STRING software. Fourteen (46.67%) of the 30 proteins were located in the complement and coagulation cascade pathway. Among 39 differentially expressed proteins, which were detected between No-ACR group and control group, 10 proteins showed a direct interaction including 9 proteins concentrated in the complement and coagulation cascade pathway. Conclusion By proteomic analysis, nine differentially expressed proteins are obtained, which may be regarded as the candidate bio-markers for ACR early diagnosis after liver transplantation. The complement and coagulation cascades system is significantly adjusted after liver transplantation, indicating this pathway plays an important role in the occurrence of ACR.
ABSTRACT
Transplant renal artery stenosis (TRAS) is a common surgical complication after kidney transplantation (KTP) and is the cause of allograft dysfunction. TRAS is a potentially curable cause of refractory hypertension and allograft dysfunction which accounts for approximately 1% to 5% of cases of post-transplant hypertension. Acute cellular rejection (ACR) is also common after KTP, which is the main cause of allograft dysfunction. Although the incidence of ACR has declined with the advent of new immunosuppressive drugs, it is still around 15% worldwide. Although each disease is frequently seen individually, seeing both together is rare. A 42-year-old man with end stage renal disease underwent KTP, and the donor was his younger brother. Four months after KTP, his serum creatinine was increased to 2.1 mg/dL, and renal biopsy showed interstitial lymphocytic infiltration and tubulitis. With the diagnosis of acute T-cell mediated rejection, steroid pulsing therapy was started, but it was resisted. Therefore thymoglobulin 60 mg (1 mg/kg/day) was administered for 6 days, but serum creatinine was 1.8 mg/dL. Abdomen magnetic resonance angiography showed TRAS, stenosis at the anastomosis site and lobar artery in the lower pole. Percutaneous transluminal angiography was performed successfully. After balloon angioplasty, the stenotic lesion showed a normal size and blood flow. The patient's renal function returned to normal levels and he is currently being followed up for 9 months.
Subject(s)
Adult , Humans , Abdomen , Allografts , Angiography , Angioplasty, Balloon , Arteries , Biopsy , Constriction, Pathologic , Creatinine , Diagnosis , Hypertension , Incidence , Kidney Failure, Chronic , Kidney Transplantation , Magnetic Resonance Angiography , Renal Artery Obstruction , Renal Artery , Siblings , T-Lymphocytes , Tissue Donors , TransplantationABSTRACT
Objective To investigate the expression of survivin in T lymphocytes that were stimulated by Con A and alloantigens in renal grafts in vitro and in vivo. Methods According to the different treatments, the experiment was divided into three parts. (1) The C57BL/6 mice splenocytes stimulated by Con A (10 mg/L) were cultured in the RPMI-1640 medium. Following the proliferation blockade or not, the expression of Survivin in the splenocytes was detected. (2) The GVHR model was established by transfusing the C57BL/6 mice splenocytes into Balb/c× C57BL/6 F1 mice, and the expression of Survivin in the donor splenocytes was detected at the different time points. (3) Seventythree cases of clinical renal allograft biopsy specimens were collected, pathologically diagnosed and classified according to the Banff 97 classification, and then the expression of Survivin was detected.Results Survivin was expressed in the CD3+ splenocytes that received Con A stimulation. The positive cell count reached the peak on the day 3, and subsequently declined. In the GVHR model, the lymphocytes infiltration and Survivin expression were detected around the portal vein and portal area on the post-splenocytes-transfused day (PSTD) 4 to 12. But on the PSTD 14, the Survivin expression could not be detected in the infiltrated lymphocytes. In the renal allograft biopsy specimens,lymphocytes did not express Survivin in 13 specimens of the group without acute cellular rejection.was difference between the two groups (P＜0. 01 ). Conclusion The activated T cells possess the capacity to express Survivin, and the expression is time-dependent. For the characteristics of Survivin expression of T cells, it may be applied as an approach to diagnose the acute cellular rejection and judge its degree and stage in the clinical allograft biopsy specimens.