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1.
J Assoc Physicians India ; 69(1): 28-31, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34227772

RESUMO

Background: Renal transplantation is the treatment of choice for selected patients with end-stage renal disease. In this study, we present our experience and follow up data of renal transplantations done at this center with special emphasis on demographic characteristics, outcome and its complications. Materials and Methods: All those patients who underwent renal transplantations and had been followed up at this center were studied and their details were recorded. For living donor transplantation, donor and recipient were evaluated in detail. Graft loss was defined as the patient became dialysis-dependent or underwent second renal transplantation. Results: A total of 250 renal transplantations were done during the study period. 16.4% of total transplantations were cadaveric transplants. Recipients mean age was 38.5±11.64 yrs and donor mean age was 42.25 ±10.79 yrs. The majority of the recipients were male (72.4%) while female donors were predominant among living donors(59.3%). Mean graft survival time was 98.2 months (95% confidence interval [CI]:72.2-114.4). Mean patient survival time was 104.5 months (95% confidence interval [CI]:82.4-126.2). Conclusion: There is increasing no. of cadaveric renal transplants due to well established deceased donation programs in the state. Our patient and graft survival are comparable. Most of the immediate graft loss was due to acute rejection and late graft loss was due to chronic antibody-mediated rejection.


Assuntos
Transplante de Rim , Adulto , Feminino , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Humanos , Índia/epidemiologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento
2.
Stem Cell Res Ther ; 12(1): 376, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215315

RESUMO

BACKGROUND: There is a huge controversy about whether xenograft or allograft in the "immune-privileged" brain needs immunosuppression. In animal studies, the prevailing sophisticated use of immunosuppression or immunodeficient animal is detrimental for the recipients, which results in a short lifespan of animals, confounds functional behavioral readout of the graft benefits, and discourages long-term follow-up. METHODS: Neuron-restricted neural progenitor cells (NPCs) were derived from human embryonic stem cells (ESCs, including H1, its gene-modified cell lines for better visualization, and HN4), propagated for different passages, and then transplanted into the brain of immunocompetent rats without immunosuppressants. The graft survivals, their cell fates, and HLA expression levels were examined over time (up to 4 months after transplantation). We compared the survival capability of NPCs from different passages and in different transplantation sites (intra-parenchyma vs. para- and intra-cerebroventricle). The host responses to the grafts were also investigated. RESULTS: Our results show that human ESC-derived neuron-restricted NPCs survive extendedly in adult rat brain parenchyma with no need of immunosuppression whereas a late-onset graft rejection seems inevitable. Both donor HLA antigens and host MHC-II expression level remain relatively low with little change over time and cannot predict the late-onset rejection. The intra-/para-cerebroventricular human grafts are more vulnerable to the immune attack than the intrastriatal counterparts. Prevention of graft hyperplasia by using hypoproliferative late passaged human NPCs further significantly extends the graft survival time. Our new data also shows that a subpopulation of host microglia upregulate MHC-II expression in response to the human graft, but fail to present the human antigen to the host immune system, suggestive of the immune-isolation role of the blood-brain barrier (BBB). CONCLUSIONS: The present study confirms the "immune privilege" of the brain parenchyma and, more importantly, unveils that choosing hypoproliferative NPCs for transplantation can benefit graft outcome in terms of both lower tumor-genic risk and the prolonged survival time without immunosuppression.


Assuntos
Transplante de Tecido Encefálico , Células-Tronco Neurais , Animais , Encéfalo , Rejeição de Enxerto , Sobrevivência de Enxerto , Xenoenxertos , Humanos , Ratos , Ratos Sprague-Dawley
3.
BMC Nephrol ; 22(1): 251, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229622

RESUMO

BACKGROUND: The ongoing coronavirus pandemic has major impacts on both patients and healthcare systems worldwide, thus creating new realities. Patients on maintenance dialysis listed for renal transplantation are a vulnerable subgroup with many comorbidities and recurring contacts with the healthcare system. Due to the COVID-19 pandemic transplant numbers have dropped considerably, further increasing waiting times in this high-risk population. On the other hand, knowledge of the severity of SARS-CoV-2 infection in immunocompromised patients, development and persistence of neutralising antibodies in such patients is just emerging. It is unclear how best to address the dilemma of postponing the life-saving transplantation. CASE PRESENTATION: We present a case report of a successful kidney transplantation only 65 days after the recipient was hospitalized for treatment of COVID-19 pneumonia. In a follow up of 9 months, we observed no signs of recurrent disease and transplant function is excellent. Monitoring SARS-CoV-2 antibody response demonstrates stable IgG levels. CONCLUSION: This reassuring case provides guidance to transplant centers how to proceed with kidney transplantation safely during the pandemic. Careful consideration of risks and benefits of the organ offer, full recovery from COVID-19 symptoms and the presence of a positive SARS-CoV-2 IgG antibody test, qualifies for kidney transplantation.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/imunologia , Falência Renal Crônica/cirurgia , Transplante de Rim , Idoso , COVID-19/complicações , Teste Sorológico para COVID-19 , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Imunossupressores/uso terapêutico , Falência Renal Crônica/complicações , Diálise Renal , SARS-CoV-2
4.
Medicine (Baltimore) ; 100(25): e26463, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160449

RESUMO

RATIONALE: Veno-occlusive disease (VOD) is characterized by painful hepatomegaly, ascites, weight gain, and jaundice with nonthrombotic, fibrous obliteration of the centrilobular hepatic veins. VOD after liver transplantation is a rare complication, with an incidence of approximately 2%; however, it can be life-threatening in severe cases. The precise etiology and mechanism of VOD after liver transplantation remains unclear. Acute cellular rejection, antibody-mediated rejection, and treatment with tacrolimus or azathioprine may be associated with the development of VOD after liver transplantation. Additionally, the optimal treatment of VOD after liver transplantation has not yet been established and focuses on supportive care. Defibrotide is an anti-ischemic and antithrombotic drug with no systemic anticoagulant effects. Moreover, only a few reports have investigated the use of defibrotide for VOD after liver transplantation, which has shown promising results. PATIENT CONCERNS: A 39-year-old woman with primary biliary cholangitis underwent living-donor liver transplantation at our center. She experienced right upper quadrant pain with increased ascites, pleural effusion, and weight gain on postoperative day 14. DIAGNOSES: Imaging and pathological tests showed no evidence of rejection or vessel complications. VOD was diagnosed clinically based on the findings of weight gain, ascites, jaundice, and pathological biopsy. INTERVENTIONS: Defibrotid, 25 mg/kg/day, was administered intravenously for 21 days. OUTCOMES: She showed complete clinical resolution of the VOD. LESSONS: Herein, we report a case of successful defibrotide treatment of VOD after living-donor liver transplantation.


Assuntos
Rejeição de Enxerto/tratamento farmacológico , Hepatopatia Veno-Oclusiva/tratamento farmacológico , Cirrose Hepática Biliar/cirurgia , Transplante de Fígado/efeitos adversos , Polidesoxirribonucleotídeos/uso terapêutico , Adulto , Aloenxertos/patologia , Biópsia , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Hepatopatia Veno-Oclusiva/diagnóstico , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Fígado/patologia , Doadores Vivos , Resultado do Tratamento
5.
Front Immunol ; 12: 535012, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093514

RESUMO

Rejection after organ transplantation is a cause of graft failure. Effectively reducing rejection and inducing tolerance is a challenge in the field of transplantation immunology. The liver, as an immunologically privileged organ, has high rates of spontaneous and operational tolerance after transplantation, allowing it to maintain its normal function for long periods. Although modern immunosuppression regimens have serious toxicity and side effects, it is very risky to discontinue immunosuppression regimens blindly. A more effective treatment to induce immune tolerance is the most sought-after goal in transplant medicine. Tregs have been shown to play a pivotal role in the regulation of immune balance, and infusion of Tregs can also effectively prevent rejection and cure autoimmune diseases without significant side effects. Given the immune characteristics of the liver, the correct use of Tregs can more effectively induce the occurrence of operational tolerance for liver transplants than for other organ transplants. This review mainly summarizes the latest research advances regarding the characteristics of the hepatic immune microenvironment, operational tolerance, Treg generation in vitro, and the application of Tregs in liver transplantation. It is hoped that this review will provide a deeper understanding of Tregs as the most effective treatment to induce and maintain operational tolerance after liver transplantation.


Assuntos
Pesquisa Biomédica/métodos , Tolerância Imunológica/imunologia , Transplante de Fígado/métodos , Linfócitos T Reguladores/imunologia , Imunologia de Transplantes/imunologia , Tolerância ao Transplante/imunologia , Pesquisa Biomédica/tendências , Previsões , Rejeição de Enxerto/imunologia , Humanos , Fígado/imunologia
7.
Transplant Proc ; 53(5): 1541-1547, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34074467

RESUMO

BACKGROUND: Acute kidney injury (AKI) is common after liver transplantation (LT). Induction with interleukin-2 receptor antagonists is often used as a "renal-sparing" strategy. The aim of this study was to assess this approach in a real-world setting in an LT center. METHODS: A retrospective cohort analysis of LTs between 2011 and 2018 was performed to assess the impact of a renal-sparing strategy using basiliximab in conjunction with mycophenolate mofetil and corticosteroids from day 0 post-LT along with delayed introduction of tacrolimus. This was compared with a group receiving tacrolimus, mycophenolate mofetil, and corticosteroids from the outset. RESULTS: The renal-sparing regimen was associated with significantly lower incidence of all-stage AKI at day 7 post-LT (36% vs 55%, P = .006) and less decline in renal function at 3 months (39% vs 57%, P = .01). No further significant differences in renal outcomes were observed at other time points on follow-up to 1 year post-LT. There was no significant difference in the incidence of acute cellular rejection, inpatient length of stay or graft survival. The decision to adopt a renal-sparing regimen was predominantly made on a clinically reactive basis within the first 24 hours post-LT in 77%, and was preordained in 23%. Cost-effectiveness analysis did not find evidence of a significant cost saving when using a renal-sparing strategy. CONCLUSION: This study provides real-world analysis of the use of a renal-sparing immunosuppression regimen in LT. Although improvements in incidence of AKI in the short term were demonstrated, this did not translate to cost savings or improved renal outcomes after 3 months.


Assuntos
Injúria Renal Aguda/prevenção & controle , Basiliximab/administração & dosagem , Imunossupressores/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Tacrolimo/administração & dosagem , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Corticosteroides/administração & dosagem , Adulto , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunossupressão/métodos , Incidência , Rim/efeitos dos fármacos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
8.
Medicina (Kaunas) ; 57(5)2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34062714

RESUMO

Monitoring kidney transplant recipients for evidence of allograft rejection is essential to lower the risk of graft loss. The traditional method relies on serial checks in serum creatinine with a biopsy of the allograft if dysfunction is suspected. This is invasive, labor-intensive and costly. As such, there is widespread interest in the use of biomarkers to provide a noninvasive approach to detecting allograft rejection. One such biomarker is donor-derived cell-free DNA (ddcf-DNA). Here, we review the methodology for the determination of the amount/fraction of ddcf-DNA, evaluate the available data of its use in kidney transplantation and render an opinion in the clinical decision-making of these patients.


Assuntos
Ácidos Nucleicos Livres , Transplante de Rim , DNA , Rejeição de Enxerto/diagnóstico , Humanos , Doadores de Tecidos
9.
Medicina (Kaunas) ; 57(5)2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-34063583

RESUMO

Kidney transplantation is the best treatment modality for end-stage kidney disease, leading to improvement in a patient's quality and quantity of life. With significant improvements in short-term outcomes, prolonging long-term allograft and patient survival remain ongoing challenges. The ability to monitor allograft function, immune tolerance and predict rejection accurately would enable personalization and better prognostication during post-transplant care. Though kidney biopsy remains the backbone of transplant diagnostics, emerging biomarkers can help detecting kidney allograft injury early enough to prevent permanent damage and detect injury before it is clinically apparent. In this review, we summarize the recent biomarkers that have shown promise in the prediction of acute rejection with a focus on antibody-mediated rejection in kidney transplantation.


Assuntos
Rejeição de Enxerto , Transplante de Rim , Anticorpos , Biomarcadores , Rejeição de Enxerto/diagnóstico , Humanos , Transplante Homólogo
10.
Medicina (Kaunas) ; 57(5)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34065914

RESUMO

Since its first detection in 1948, donor-derived cell-free DNA (dd-cfDNA) has been employed for a myriad of indications in various medical specialties. It has had a far-reaching impact in solid organ transplantation, with the most widespread utilization in kidney transplantation for the surveillance and detection of allograft rejection. The purpose of this review is to track the arc of this revolutionary test-from origins to current use-along with examining challenges and future prospects though the lens of transplant nephrology.


Assuntos
Ácidos Nucleicos Livres , Transplante de Rim , Transplantes , Rejeição de Enxerto , Humanos , Doadores de Tecidos
11.
Clin Lab ; 67(6)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34107638

RESUMO

BACKGROUND: The aim of the study was to explore the association of peripheral leukocyte cell population data (CPD) with acute rejection episodes (ARE) after kidney transplantation surgery and search for potential parameters which contribute to the assessment of the occurrence of ARE. METHODS: A total of 68 patients with kidney transplants were classified into two groups according to the occurrence of ARE or not within three months after transplantation surgery (32 in ARE and 36 in non-ARE group). Hematological parameters including leukocyte CPD and serum biochemical indicators of renal function during occurrence of ARE were collected. The differences of CPD between the two groups and the association of CPD with occurrence of ARE were analyzed by SPSS software. RESULTS: Between ARE and non-ARE group, CPD parameters showed significant differences involving neutrophils, lymphocytes, and monocytes (Ne-V-sd, Ne-UMS-sd, Ly-V, Ly-MS, Ly-UMS, Ly-LS, and Mo-UMS). Ne-UMS-sd and Ly-UMS made the strongest contribution in discrimination of ARE occurrence. Ly-UMS had the largest area under the ROC (receiver operating characteristic) curve (AUC = 0.756). Meanwhile, the AUC of Ne-UMS-sd combined with Ly-UMS reached 0.823. In the ARE group, Ne-UMS-sd and Ly-UMS were inversely and linearly associated with eGFR (r = -0.527, p = 0.002; r = -0.436, p = 0.013, respectively). CONCLUSIONS: Ne-UMS-sd and Ly-UMS may be useful for the diagnosis of acute rejection episodes after kidney transplantation.


Assuntos
Transplante de Rim , Rejeição de Enxerto/diagnóstico , Humanos , Transplante de Rim/efeitos adversos , Leucócitos , Linfócitos , Neutrófilos , Curva ROC
12.
Int J Mol Sci ; 22(11)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34063776

RESUMO

Calcineurin inhibitors are highly efficacious immunosuppressive agents used in pediatric kidney transplantation. However, calcineurin inhibitor nephrotoxicity (CNIT) has been associated with the development of chronic renal allograft dysfunction and decreased graft survival. This study evaluated 37 formalin-fixed paraffin-embedded biopsies from pediatric kidney transplant recipients using gene expression profiling. Normal allograft samples (n = 12) served as negative controls and were compared to biopsies exhibiting CNIT (n = 11). The remaining samples served as positive controls to validate CNIT marker specificity and were characterized by other common causes of graft failure such as acute rejection (n = 7) and interstitial fibrosis/tubular atrophy (n = 7). MiRNA profiles served as the platform for data integration. Oxidative phosphorylation and mitochondrial dysfunction were the top molecular pathways associated with overexpressed genes in CNIT samples. Decreased ATP synthesis was identified as a significant biological function in CNIT, while key toxicology pathways included NRF2-mediated oxidative stress response and increased permeability transition of mitochondria. An integrative analysis demonstrated a panel of 13 significant miRNAs and their 33 CNIT-specific gene targets involved with mitochondrial activity and function. We also identified a candidate panel of miRNAs/genes, which may serve as future molecular markers for CNIT diagnosis as well as potential therapeutic targets.


Assuntos
Biomarcadores/metabolismo , Inibidores de Calcineurina/toxicidade , Sobrevivência de Enxerto/genética , Nefropatias/induzido quimicamente , Nefropatias/genética , Transcriptoma/genética , Biópsia/métodos , Inibidores de Calcineurina/uso terapêutico , Criança , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/genética , Humanos , Imunossupressores/uso terapêutico , Imunossupressores/toxicidade , Rim/efeitos dos fármacos , Rim/metabolismo , Transplante de Rim/efeitos adversos , MicroRNAs/genética , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Transplantados , Transplante Homólogo/métodos
13.
Trials ; 22(1): 414, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34167567

RESUMO

BACKGROUND: Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent in low immunological risk kidney transplant recipients. However, the role of IL2-RA in the setting of tacrolimus-based immunosuppression has not been fully investigated. AIMS: To compare different induction therapeutic strategies with 2 doses of basiliximab vs. no induction in low immunologic risk kidney transplant recipients as per KFSHRC protocol. METHODS: Prospective, randomized, double blind, non-inferiority, controlled clinical trial EXPECTED OUTCOMES: 1. Primary outcomes: Biopsy-proven acute rejection within first year following transplant 2. SECONDARY OUTCOMES: a. Patient and graft survival at 1 year b. eGFR at 6 months and at 12 months c. Emergence of de novo donor-specific antibodies (DSAs) TRIAL REGISTRATION: The study has been prospectively registered at clinicaltrials.gov (NTC: 04404127). Registered on 27 May 2020.


Assuntos
Transplante de Rim , Basiliximab , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tacrolimo
15.
Stud Health Technol Inform ; 281: 188-192, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34042731

RESUMO

This paper investigates the clinical attributes that contribute to kidney graft failure following live and deceased donor transplantation using an association rule mining approach. The generated rules are used to analyze the distinctive co-occurrence of attributes for those with or without all-cause graft failure. Analysis of a kidney transplantation dataset acquired from the Scientific Registry of Transplant Recipients that included over 95000 deceased and live donor recipients over 5-years was performed. Using an association rule mining approach, we were able to confirm established risk factors for graft loss after live and deceased donor transplantation and identify novel combinations of factors that may have implications for clinical care and risk prediction post kidney transplantation. Using lift as the metric to evaluate association rules, our results indicate that advanced recipient age (i.e. over 60 years), end stage kidney disease due to diabetes, the presence of recipient peripheral vascular disease and recipient coronary artery disease have a high likelihood of graft failure within 5 years after transplantation.


Assuntos
Transplante de Rim , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Rim , Doadores Vivos , Fatores de Risco , Doadores de Tecidos , Transplantados , Resultado do Tratamento
17.
Curr Opin Ophthalmol ; 32(4): 331-337, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33989234

RESUMO

PURPOSE OF REVIEW: Immune rejection after corneal transplantation is a major risk for graft failure. We aim to summarize recent advances in the understanding and management of graft rejection. RECENT FINDINGS: Immune rejection remains the leading cause of graft failure in penetrating keratoplasty (PKP). While ABO blood type and sex match between donor and recipient may reduce rejection, human leucocyte antigens class II matching in a randomized study did not reduce the risk of rejection in high-risk PKP. Compared with PKP, deep anterior lamellar keratoplasty, descemet stripping automated endothelial keratoplasty, and descemet membrane endothelial keratoplasty have lower immune rejection rates of 1.7-13%, 5-11.4%, and 1.7-2.8%, respectively, based on long-term (5 years and more) studies. Whether immune rejection is a major risk factor for graft failure in these lamellar keratoplasties is unclear. While there have not been major advances in the systemic management of graft rejection, topical nonsteroid agents such as tacrolimus and anti-vascular endothelial growth factor have shown promise in high-risk cases. SUMMARY: Immune rejection remains the leading cause of graft failure in PKP. Lamellar keratoplasties have significantly lower rejection rates compared with PKP. The significance of rejection in the failure of lamellar grafts warrants further investigation.


Assuntos
Doenças da Córnea/cirurgia , Transplante de Córnea/efeitos adversos , Rejeição de Enxerto/imunologia , Imunidade Celular , Sobrevivência de Enxerto , Humanos , Fatores de Risco , Doadores de Tecidos
18.
BMC Med Res Methodol ; 21(1): 104, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33992081

RESUMO

BACKGROUND: Tacrolimus is given post-kidney transplant to suppress the immune system, and the amount of drug in the body is measured frequently. Higher variability over time may be indicative of poor drug adherence, leading to more adverse events. It is important to account for the variation in Tacrolimus, not just the average change over time. METHODS: Using data from the University of Colorado, we compare methods of assessing how the variability in Tacrolimus influences the hazard of de novo Donor Specific Antibodies (dnDSA), an early warning sign of graft failure. We compare multiple joint models in terms of fit and predictive ability. We explain that the models that account for the individual-specific variability over time have the best predictive performance. These models allowed each patient to have an individual-specific random error term in the longitudinal Tacrolimus model, and linked this to the hazard of dnDSA model. RESULTS: The hazard for the variance and coefficient of variation (CV) loading parameter were greater than 1, indicating that higher variability of Tacrolimus had a higher hazard of dnDSA. Introducing the individual-specific variability improved the fit, leading to more accurate predictions about the individual-specific time-to-dnDSA. CONCLUSIONS: We showed that the individual's variability in Tacrolimus is an important metric in predicting long-term adverse events in kidney transplantation. This is an important step in personalizing the dosage of TAC post-transplant to improve outcomes post-transplant.


Assuntos
Rejeição de Enxerto , Isoanticorpos , Biomarcadores , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Imunossupressores/efeitos adversos , Estudos Retrospectivos , Tacrolimo/efeitos adversos
19.
Cancer Sci ; 112(7): 2592-2606, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33938090

RESUMO

Immunotherapy has revolutionized cancer treatment, however, not all tumor types and patients are completely responsive to this approach. Establishing predictive pre-clinical models would allow for more accurate and practical immunotherapeutic drug development. Mouse models are extensively used as in vivo system for biomedical research. However, due to the significant differences between rodents and human, it is impossible to translate most of the findings from mouse models to human. Pharmacological development and advancing personalized medicine using patient-derived xenografts relies on producing mouse models in which murine cells and genes are substituted with their human equivalent. Humanized mice (HM) provide a suitable platform to evaluate xenograft growth in the context of a human immune system. In this review, we discussed recent advances in the generation and application of HM models. We also reviewed new insights into the basic mechanisms, pre-clinical evaluation of onco-immunotherapies, current limitations in the application of these models as well as available improvement strategies. Finally, we pointed out some issues for future studies.


Assuntos
Modelos Animais de Doenças , Imunoterapia , Neoplasias/terapia , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Anticorpos Monoclonais/uso terapêutico , Citocinas/metabolismo , Desenvolvimento de Medicamentos , Engenharia Genética , Rejeição de Enxerto/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Imunoterapia Adotiva/métodos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Células Matadoras Naturais/imunologia , Camundongos , Camundongos SCID , Neoplasias/imunologia , Medicina de Precisão , Pesquisa Médica Translacional , Transplante Heterólogo
20.
Transplant Proc ; 53(5): 1514-1518, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33994188

RESUMO

BACKGROUND: Borderline changes suspicious for acute T-cell-mediated rejection (BC) are frequently seen on biopsy specimens, but their clinical significance and clinical management are still controversial. Our goal was to compare clinical outcomes of kidney transplant recipients with biopsy-proven BC vs acute T-cell-mediated rejection (aTCMR) and the influence of treating BC on graft outcomes. METHODS: A retrospective cohort study was performed in all kidney transplant recipients with biopsy-proven BC and aTCMR between January 2012 and December 2018, according to Banff 2017 criteria; patients with concomitant antibody-mediated rejection were excluded. RESULTS: We included 85 patients, 30 with BC (35.3%) and 55 with aTCMR (64.7%). There was no difference between groups regarding demographics, HLA matching and sensitization, immunosuppression, or time of transplant. Treatment with steroids was started in 15 patients with BC (50%) and in all patients with aTCMR, with 4 of the latter additionally receiving thymoglobulin (7.2%). At 1 year post biopsy, overall graft survival was 71%, and despite presenting better estimated glomerular filtration rate (eGFR) at biopsy (33.3 ± 23.4 vs 19.9 ± 13.2 mL/min/1.73 m2, P = .008), patients in the BC group presented the same graft survival as the aTCMR group according to Kaplan-Meyer survival curves. When analyzing the BC group (n = 30) and comparing the patients who were treated (n = 15) vs a conservative approach (n = 15), graft survival at 1 year was 87% for treated patients and 73% for nontreated patients (P = .651), with no difference in eGFR for patients with functioning graft. However, at longer follow-up, survival curves showed a trend for better graft survival in treated patients (70.2 ± 9.2 vs 38.4 ± 8.4 months, P = .087). CONCLUSION: Our study showed that patients with BC did not present better graft survival or graft function at 1 year after biopsy or at follow-up compared with the aTCMR group, despite better eGFR at diagnosis. We found a trend for better graft survival in patients with BC treated with steroids compared with a conservative approach. These results reinforce the importance of borderline changes in graft outcomes and that the decision to treat can influence long-term outcomes.


Assuntos
Biópsia/estatística & dados numéricos , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Transplante de Rim/efeitos adversos , Adulto , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/imunologia , Humanos , Imunossupressão/métodos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Diferença Mínima Clinicamente Importante , Período Pós-Operatório , Estudos Retrospectivos , Transplantes/patologia , Resultado do Tratamento , Adulto Jovem
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