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1.
Medicine (Baltimore) ; 98(48): e18244, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770287

RESUMO

BACKGROUND: We investigated the effects of propofol vs desflurane on ischemia and reperfusion injury (IRI)-induced inflammatory responses, especially in matrix metalloproteinase-9 (MMP-9) downregulation and heme oxygenase-1 (HO-1) upregulation, which may result in different clinical outcomes in liver transplant recipients. METHODS: Fifty liver transplant recipients were randomized to receive propofol-based total intravenous anesthesia (TIVA group, n = 25) or desflurane anesthesia (DES group, n = 25). We then measured the following: perioperative serum cytokine concentrations (interleukin 1 receptor antagonist [IL-1RA], IL-6, IL-8, and IL-10); MMP-9 and HO-1 mRNA expression levels at predefined intervals. Further, postoperative outcomes were compared between the 2 groups. RESULTS: The TIVA group showed a significant HO-1 level increase following the anhepatic phase and a significant MMP-9 reduction after reperfusion, in addition to a significant increase in IL-10 levels after the anhepatic phase and IL-1RA levels after reperfusion. Compared to DES patients, TIVA patients showed a faster return of the international normalized ratio to normal values, lower plasma alanine aminotransferase concentrations 24 hours after transplantation, and fewer patients developing acute lung injury. Moreover, compared with DES patients, TIVA patients showed a significant reduction in serum blood lactate levels. However, there were no differences in postoperative outcomes between the two groups. CONCLUSION: Propofol-based TIVA attenuated inflammatory response (elevated IL-1RA and IL-10 levels), downregulated MMP-9 response, and increased HO-1 expression with improved recovery of graft function and better microcirculation compared with desflurane anesthesia in liver transplant recipients.


Assuntos
Desflurano , Transplante de Fígado , Propofol , Traumatismo por Reperfusão , Adulto , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/efeitos adversos , Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/efeitos adversos , Desflurano/administração & dosagem , Desflurano/efeitos adversos , Feminino , Heme Oxigenase-1/análise , Humanos , Proteína Antagonista do Receptor de Interleucina 1/análise , Interleucina-10/análise , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Masculino , Metaloproteinase 9 da Matriz/análise , Período Pós-Operatório , Propofol/administração & dosagem , Propofol/efeitos adversos , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/etiologia , Imunologia de Transplantes
2.
Rev. Pesqui. (Univ. Fed. Estado Rio J., Online) ; 11(5): 1202-1207, out.-dez. 2019. tab
Artigo em Inglês, Português | LILACS, BDENF - Enfermagem | ID: biblio-1022269

RESUMO

Objetivo: Avaliar as características clínicas e imunológica dos receptores de transplante renal. Métodos: estudo documental e retrospectivo, realizado em um Ambulatório do Hospital Geral de Fortaleza, Fortaleza, Ceará, Brasil, com pacientes internados no período de junho de 2012 a junho de 2014. A amostra foi composta por 300 pacientes submetidos ao transplante renal. As variáveis preditoras de interesse, foram subdivididas em: características prétransplante, características pós-transplante e características imunológicas. Utilizou-se testes de Pearson e Spearman para avaliar correlação entre variáveis. Resultados: Houve predomínio de pacientes do sexo masculino (65%), com faixa etária entre 44 e 56 anos (31,4%). Demonstrou-se relação estatisticamente significante entre o DSA e a disfunção do enxerto (p<0,04), Rejeição celular o Painel Reativo classe I (p< 0,05), o tempo de internação e a disfunção do enxerto (p<0,001) e entre o entre o HLA e o MISMATCH. Conclusão: Aponta-se a necessidade de um acompanhamento crítico e individualizado do paciente transplantado por parte dos profissionais para garantir o sucesso do transplante a longo prazo


Objective: The study's purpose has been to assess both clinical and immunological characteristics of renal transplant recipients. Methods: It is a documentary and retrospective study that was performed at the renal transplantation ambulatory from the Hospital Geral de Fortaleza (HGF), Fortaleza city, Ceará State, with patients hospitalized from June 2012 to June 2014. The sample consisted of 300 patients submitted to renal transplantation. The predictive variables of interest were subdivided in the following categories: pre-transplant characteristics, post-transplant characteristics and immunological characteristics. Pearson and Spearman tests were used to evaluate the correlation between variables. Results: There was a predominance of male patients (65%), with ages ranging from 44 to 56 years (31.4%). A statistically significant relationship was found between the Donor-Specific Antibody and Delayed Graft Function (p<0.04), Cellular Rejection and PanelReactive Antibody class I (p<0.05), duration of hospitalization and Delayed Graft Function (p<0.001) and also between the Human Leukocyte Antigen and MISMATCH. Conclusion: It is pointed out the need for a critical and individualized follow-up of the transplanted patient by the professionals to guarantee the long-term transplantation success


Objetivo: Evaluar las características clínicas e inmunológicas de lós receptores de trasplante renal. Métodos: estudio documental y retrospectivo realizado en una clínica del Hospital General de Fortaleza, Fortaleza, Ceará, Brasil, con pacientes ingresados desde junio de 2012 a junio de 2014. La muestra fue de 300 pacientes sometidos a trasplante de riñón. Las variables predictoras de interés, fueron subdivididas en: características pretrasplante, características post-transplante y características inmunológicas. Se utilizaron pruebas de Pearson y Spearman para evaluar la correlación entre variables. Resultados: Hubo un predominio de pacientes del sexo masculino (65%), con edades comprendidas entre 44 y 56 años (31,4%). Se demostró una relación estadísticamente significativa entre el DSA y la disfunción del injerto (p <0,04), el rechazo celular del panel reactivo clase I (p <0,05), el tiempo de internación y la disfunción del injerto (p <0,001) y entre el HLA y el MISMATCH. Conclusión: Se apunta la necesidad de un acompañamiento crítico e individualizado del paciente trasplantado por parte de los profesionales para garantizar el éxito del trasplante a largo plazo


Assuntos
Humanos , Masculino , Feminino , Imunologia de Transplantes , Transplante de Rim/estatística & dados numéricos , Continuidade da Assistência ao Paciente/estatística & dados numéricos , Brasil , Rejeição de Enxerto/epidemiologia
3.
Khirurgiia (Mosk) ; (9): 80-85, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31532171

RESUMO

This article discusses the need to implement effective methods for monitoring immune status and rehabilitation of patients after kidney transplantation. Induction of immunological tolerance which allows minimizing or even completely canceling supportive immunosuppressive therapy is one of the key tasks in the field of organ transplantation. Regulatory T-cells (TREGs) play an important role in maintaining immunological homeostasis, including limiting kidney transplant rejection, and potentially contribute to the development of immunological tolerance. At the same time, for the introduction of TREG therapy into clinical practice, it is necessary to overcome a number of unsolved problems, such as induction and cultivation of a sufficient number of TREG cells for therapeutic action as well as reducing the risks associated with TREG conversion to effector lymphocytes or an undesirable non-specific immunosuppressive effect. This review examines both the impact of common post-transplant pharmacological immunosuppression approaches on TREGs and the therapeutic potential of TREG cell cultures in prevention of kidney transplant rejection. The questions of ex vivo TREG manufacturing process and possible threats of applying cell technologies in this branch of transplantology were considered.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Transplante de Rim/efeitos adversos , Linfócitos T Reguladores/imunologia , Rejeição de Enxerto/etiologia , Humanos , Tolerância Imunológica/imunologia , Imunossupressão/métodos , Imunossupressores/uso terapêutico , Transplante de Rim/reabilitação , Imunologia de Transplantes/imunologia
4.
Khirurgiia (Mosk) ; (8): 59-62, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31464276

RESUMO

The use of allogenic materials in reconstructive surgery is of great scientific interest due to high availability of donor tissues. The positive aspects of allogenous tissue transplantation are complicated by the histological incompatibility of donor tissue and recipient organism. This incompatibility results hypersensitivity reaction towards the allogenous transplant followed by rejection of allogenic tissue and even death in some cases. Cellular biological incompatibility may be managed by decellularization of allogenous organs and tissues prior to transplantation. The improvement of decellularization techniques will facilitate application of allogenous tissues in complex reconstructive procedures and significantly increase the capabilities of reconstructive surgery.


Assuntos
Aloenxertos/imunologia , Células/imunologia , Engenharia Tecidual/métodos , Imunologia de Transplantes , Transplante Homólogo/métodos , Aloenxertos/citologia , Rejeição de Enxerto/imunologia , Procedimentos Cirúrgicos Reconstrutivos , Tecidos Suporte , Imunologia de Transplantes/imunologia
5.
Am Surg ; 85(6): 631-637, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31267905

RESUMO

The field of vascularized composite allotransplantation (VCA) has moved from a highly experimental procedure to, at least for some patients, one of the best treatment alternatives for catastrophic tissue loss or dysfunction. Although the worldwide experience is still limited, progress has been made in translation to the clinic, and hand transplantation was recently designated standard of care and is now covered in full by the British Health System. This progress is tempered by the long-term challenges of systemic immunosuppression, and the rapidly evolving indications for VCA such as urogenital transplantation. This update will cover the state of and recent changes in the field, and an update of the Louisville VCA program as our initial recipient, the first person to receive a hand transplant in the United States celebrates the 20th anniversary of his transplant. The achievements and complications encountered over the last two decades will be reviewed. In addition, potential directions for research and collaboration as well as practical issues of how third party payers and funding are affecting growth of the field are presented.


Assuntos
Imunossupressores/administração & dosagem , Procedimentos Cirúrgicos Reconstrutivos/métodos , Alotransplante de Tecidos Compostos Vascularizados/métodos , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Masculino , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/fisiopatologia , Prognóstico , Sociedades Médicas , Imunologia de Transplantes/fisiologia , Alotransplante de Tecidos Compostos Vascularizados/efeitos adversos
7.
Blood ; 134(11): 892-899, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31270102

RESUMO

The use of anti-thymocyte globulin (ATG) has represented the standard of care in graft-versus-host disease (GVHD) prophylaxis in patients undergoing a mismatched unrelated donor (MMUD) transplant. The safety and feasibility of posttransplant cyclophosphamide (PTCY) in this setting have been reported recently, but no study has compared the outcomes of PTCY vs ATG in 9/10 MMUD transplants. Using the registry data of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we performed a matched-pair analysis comparing those 2 strategies in a 9/10 MMUD setting. Ninety-three patients receiving PTCY were matched with 179 patients receiving ATG. A significantly lower incidence of severe acute GVHD was observed with PTCY compared with ATG. Recipients of the former also showed higher leukemia-free survival and GVHD/relapse-free survival (GRFS). When performing a subgroup analysis including patients receiving peripheral blood stem cells, being in complete remission, or receiving the same associated immunosuppressive agents, superiority of PTCY over ATG was confirmed. Similar to the haploidentical setting, use of PTCY is an effective anti-GVHD prophylaxis in the 9/10 MMUD transplant. Use of PTCY may also provide better outcomes in long-term disease control. These results need confirmation in large prospective randomized trials.


Assuntos
Soro Antilinfocitário/administração & dosagem , Ciclofosfamida/administração & dosagem , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Condicionamento Pré-Transplante/métodos , Doadores não Relacionados , Adulto , Idoso , Soro Antilinfocitário/efeitos adversos , Tipagem e Reações Cruzadas Sanguíneas/efeitos adversos , Ciclofosfamida/efeitos adversos , Esquema de Medicação , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Teste de Histocompatibilidade/efeitos adversos , Humanos , Leucemia Mieloide Aguda/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversos , Imunologia de Transplantes , Transplante Homólogo , Adulto Jovem
8.
Nephrology (Carlton) ; 24(10): 997-1000, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31335997

RESUMO

Tissue typing is the process by which an individual's human leukocyte antigens (HLA) are determined. In transplantation, this vital process allows the immunologic or rejection risk of a donor-recipient pairing to be assessed through reviewing their HLA matching and whether any anti-HLA antibodies present in recipient serum are donor specific. Tissue typing has increased in sophistication over time which has allowed a deeper appreciation of the antigenically important parts of HLA and increased the complexity of determining immunologic risk.


Assuntos
Rejeição de Enxerto , Teste de Histocompatibilidade/métodos , Transplante de Rim/métodos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Imunologia de Transplantes
9.
Rev. enferm. Inst. Mex. Seguro Soc ; 27(3): 154-162, Jul-Sep 2019. tab, graf
Artigo em Espanhol | LILACS, BDENF - Enfermagem | ID: biblio-1047306

RESUMO

Introducción: el trasplante renal (TR) es la terapia de elección en la mayoría de los pacientes con insuficiencia renal crónica terminal. El conocimiento cada vez más amplio de la inmunología, la mejoría en las técnicas quirúrgicas, el uso de mejores fármacos inmunosupresores y los cuidados en el seguimiento posterior al trasplante han permitido reducir la incidencia de pérdida de injerto y han mejorado la calidad de vida de los pacientes luego del TR. Objetivo: identificar las complicaciones más frecuentes en las primeras 48 horas en pacientes con TR en un hospital de tercer nivel de atención. Métodos: estudio descriptivo y transversal en una muestra aleatoria de 41 pacientes con TR registrados del 5 de enero al 5 de septiembre de 2017 en un hospital de tercer nivel de atención de la ciudad de Veracruz. La información se recabó del expediente clínico como unidad de análisis. Los datos se analizaron con medidas de tendencia central y dispersión. Resultados: el 65.9% fueron hombres; la edad promedio fue de 35 ± 11.3 años. La principal causa de lesión renal crónica fue etiología no determinada (53.7%) e hipoplasia renal (14.6%). El motivo de egreso fue por mejoría en 97.6%. Solo en 10% de los pacientes se presentaron complicaciones, principalmente trombosis segmentada de vena safena interna (30%), trombosis de injerto (3%), trombosis venosa profunda de segmento femoral (2%) y disminución del flujo vascular renal de polo inferior (2%). Conclusión: las complicaciones que se presentaron en los pacientes postrasplantados de riñón en las primeras 48 horas fueron las de tipo vascular.


Introduction: Kidney transplantation is the therapy of choice in the majority of patients with end-stage chronic renal failure. The increasing knowledge of immunology, the improvement in surgical techniques, the use of better immunosuppressive drugs and post-transplant follow-up care have reduced the incidence of graft loss and improved the patients' quality of life after kidney transplantation. Objective: To identify the most frequent complications in the first 48 hours in patients who underwent kidney transplantation in a third level hospital. Methods: Cross-sectional, descriptive study in a random sample of 41 patients with kidney transplantation registered from January 5 to September 5, 2017, in a third level hospital from the city of Veracruz. The information was collected from the clinical record as an analysis unit. Data were analyzed with measures of central tendency and dispersion. Results: 65.9% of patients were male; the average age was 35 ± 11.3 years. The main cause of chronic renal injury was undetermined etiology (53.7%) and renal hypoplasia (14.6%). The reason for discharge was improved health in 97.6% of patients. Only 10% of patients presented complications, mainly internal saphenous vein thrombosis (30%), graft thrombosis (3%), deep venous thrombosis of the femoral segment (2%) and decreased renal vascular flow of the lower pole (2%). Conclusion: The complications that occurred in patients who underwent kidney transplantation in the first 48 hours were vascular.


Assuntos
Humanos , Qualidade de Vida , Imunologia de Transplantes , Epidemiologia Descritiva , Estudos Transversais , Transplante de Rim/efeitos adversos , Insuficiência Renal Crônica , Lesão Renal Aguda , Rejeição de Enxerto , Hospitais Públicos , Hospitais Especializados , Imunossupressores , México
10.
Int J Immunogenet ; 46(5): 307-320, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31183978

RESUMO

The detection and semiquantitative measurement of circulating human leucocyte antigen (HLA)-specific antibodies is essential for the management of patients before and after transplantation. In addition, the pretransplant cross-match to assess the reactivity of recipient HLA antibody against donor lymphocytes has long been the gold standard to prevent hyperacute rejection. Whilst both of these tests assume that recipient HLA-specific antibody is the only variable in the assessment of transplant risk, this is not the case. Transplant immunologists recognize that some HLA antigens are expressed at levels a magnitude lower than others (e.g., HLA-C, HLA-DQ), but within loci, and between different cell types there are many factors that influence HLA expression in both resting and activated cells. HLA is not usually expressed without the specific promoter proteins NLRC5, for HLA class I, and CIITA, for class II. The quantity of HLA protein production is then affected by factors including promoter region polymorphisms, alternative exon splice sites, methylation and microRNA-directed degradation. Different loci are influenced by multiple combinations of these control mechanisms making prediction of HLA regulation difficult, but an ability to measure the cellular expression of each HLA antigen, in conjunction with knowledge of circulating HLA-specific antibody, would lead to a more informed algorithm to assess transplant risk.


Assuntos
Regulação da Expressão Gênica , Antígenos HLA/genética , Antígenos HLA/imunologia , Membrana Celular/imunologia , Membrana Celular/metabolismo , Epigênese Genética , Variação Genética , Humanos , Isoanticorpos/imunologia , Polimorfismo Genético , Regiões Promotoras Genéticas , Processamento Pós-Transcricional do RNA , Imunologia de Transplantes
11.
Immunobiology ; 224(4): 485-489, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31204065

RESUMO

Parathyroid allotransplantation is increasingly practiced for patients who have permanent hypoparathyroidsm. Parathyroid allotransplantation success is varied, and no defined criteria about immunologic monitoring for pre-/post-transplantation follow-up. This study sought to evaluate the possible role of immunological tests. Four unrelated recipients and one living donor who have chronic kidney disease were evaluated for HLA-typing, PRA, CXM tests to conduct parathyroid allotransplantation. Parathyroid glands were obtained and resected from the donor, then cells were isolated and cryopreserved. Upon histologic examination, cells were cultivated and injected into muscle of four recipients. Recipient's were followed for parathormone and calcium levels for four years. PRA screening were monitored and de novo DSA was evaluated as well. In two of the recipients, allografts continued to be functional more than four years. In one recipient, allograft remained functional for two years and another recipient lost function after one year. Two out four were negative for de novo DSA and three out of four of the recipients remained negative for PRA. Neither HLA-matching nor de novo DSA positivity and PRA screenings seems significant for successfull parathyroid allotransplantation. This study has considerable potential for immunological monitoring of parathyroid allotransplantation.


Assuntos
Antígenos HLA/imunologia , Teste de Histocompatibilidade , Isoanticorpos/imunologia , Glândulas Paratireoides/imunologia , Glândulas Paratireoides/transplante , Doadores de Tecidos , Adulto , Alelos , Biomarcadores , Feminino , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Antígenos HLA/genética , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/metabolismo , Imunologia de Transplantes , Transplante Homólogo
12.
JAMA ; 321(22): 2183-2192, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31184739

RESUMO

Importance: Evidence regarding associations of blood donor sex with mortality among red blood cell transfusion recipients is conflicting. Objective: To study associations of donor sex and prior pregnancy with mortality of transfusion recipients. Design, Setting, and Participants: Data from 3 retrospective cohorts of transfusion recipients (the Kaiser Permanente Northern California [KPNC] and Recipient Epidemiology and Donor Evaluation Study-III [REDS-III] databases of data from January 2013 to December 2016 and the Scandinavian Donations and Transfusions [SCANDAT] database with data from January 2003 to December 2012) were analyzed. Final dates of follow-up were December 31, 2016, for the KPNC and REDS-III cohorts and December 31, 2012, for the SCANDAT cohort. Stratified Cox regression models were used to estimate associations between donor exposure groups with risk of mortality, adjusting for the number of red blood cell unit transfusions. Exposures: The number of transfused red blood cell units from female donors, previously pregnant donors, and sex-discordant donors (male donor and female recipient or female donor and male recipient). Main Outcomes and Measures: In-hospital mortality. Results: The study population included 34 662 patients (mean age, 69 years; 18 652 [54%] women) from the KPNC cohort, 93 724 patients (mean age, 61 years; 48 348 [52%] women) from the REDS-III cohort, and 918 996 patients (mean age, 72 years; 522 239 [57%] women) from the SCANDAT cohort. The median number of red blood cell transfusions per patient was 3 in the KPNC cohort, 2 in the REDS-III cohort, and 3 in the SCANDAT cohort. The percentage of transfusions from previously pregnant or parous donors was 9% in the KPNC cohort, 18% in the REDS-III cohort, and 25% in the SCANDAT cohort. The percentage of transfusions in the 3 cohorts from female donors ranged from 39% to 43%, from previously pregnant or parous donors ranged from 9% to 25%, and from sex-discordant donors ranged from 44% to 50%. There were 3217 in-hospital deaths in the KPNC cohort, 8519 in the REDS-III cohort, and 198 537 in the SCANDAT cohort. There were no statistically significant associations between any of the 3 donor exposures and in-hospital mortality in the 3 cohorts. Hazard ratios for in-hospital mortality per transfused unit from female donors were 0.99 (95% CI, 0.96-1.03) for the KPNC cohort, 1.00 (95% CI, 0.99-1.01) for the REDS-III cohort, and 1.00 (95% CI, 0.99-1.00) for the SCANDAT cohort. For units from previously pregnant or parous female donors, hazard ratios were 1.00 (95% CI, 1.00-1.01) for the KPNC cohort, 1.01 (95% CI, 0.98-1.03) for the REDS-III cohort, and 1.00 (95% CI, 1.00-1.01) for the SCANDAT cohort. For units from sex-discordant transfusions, hazard ratios were 1.02 (95% CI, 0.99-1.05) for the KPNC cohort, 0.99 (95% CI, 0.98-1.00) for the REDS-III cohort, and 1.00 (95% CI, 0.99-1.00) for the SCANDAT cohort. Conclusions and Relevance: Among red blood cell transfusion recipients, transfusions from female, previously pregnant, or sex-discordant donors were not significantly associated with increased mortality.


Assuntos
Doadores de Sangue , Transfusão de Eritrócitos/mortalidade , Gravidez , Adulto , Idoso , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Análise de Sobrevida , Imunologia de Transplantes , Adulto Jovem
14.
Transplant Rev (Orlando) ; 33(3): 130-136, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31130302

RESUMO

Current immunosuppressive (IS) regimens used to prevent organ allograft rejection have well-recognized side effects, that include enhanced risk of infection and certain types of cancer, metabolic disorders, cardiovascular disease, renal complications and failure to control chronic allograft rejection. The life-long dependency of patients on these IS agents reflects their inability to induce donor-specific tolerance. Extensive studies in rodent and non-human primate models have demonstrated the ability of adoptively-transferred regulatory immune cells (either regulatory myeloid cells or regulatory T cells) to promote transplant tolerance. Consequently, there is considerable interest in the potential of regulatory immune cell therapy to allow safe minimization/complete withdrawal of immunosuppression and the promotion of organ transplant tolerance in the clinic. Here, we review the properties of regulatory dendritic cells (DCreg) with a focus on the approaches being taken to generate human DCreg for clinical testing. We also document the early phase clinical trials that are underway to assess DCreg therapy in clinical organ transplantation as well as in autoimmune disorders.


Assuntos
Células Dendríticas , Transplante de Órgãos , Imunologia de Transplantes , Pesquisa Biomédica , Humanos
16.
Hum Immunol ; 80(8): 561-567, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31010696

RESUMO

Antibodies against two G-protein coupled receptors (GPCRs), angiotensin II type 1 receptor (AT1R) and endothelin A receptor (ETAR) are among a growing number of autoantibodies that are found to be associated with allograft dysfunction. AT1R antibodies (AT1Rabs) and ETAR antibodies (ETARabs) have been shown to activate their target receptors and affect signaling pathways. Multiple single center reports have shown an association between presence of these antibodies and acute or chronic rejection and graft loss in kidney, heart, liver, lung and composite tissue transplantations. However, the characteristics of patients that are most likely to develop adverse outcomes, the phenotypes associated with graft damage solely due to these antibodies, and the antibody titer required to cause dysfunction are areas that remain controversial. This review compiles existing knowledge on the effect of antibodies against GPCRs in other diseases in order to bridge the gap in knowledge within transplantation biology. Future areas for research are highlighted and include the need for functional assays and treatment protocols for transplant patients who present with AT1Rabs and ETARabs. Understanding how antibodies that activate GPCRs influence transplantation outcome will have direct clinical implications for preemptive evaluation of transplant candidates as well as the post-transplant care of organ recipients.


Assuntos
Autoanticorpos/metabolismo , Rejeição de Enxerto/imunologia , Transplante de Órgãos , Receptor Tipo 1 de Angiotensina/imunologia , Receptor de Endotelina A/imunologia , Animais , Humanos , Fenótipo , Transdução de Sinais , Imunologia de Transplantes
17.
Transplant Rev (Orlando) ; 33(3): 115-129, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31027947

RESUMO

Research in transplant immunology using non-human primate (NHP) species to evaluate immunologic strategies to prevent rejection and prolong allograft survival has yielded results that have translated successfully into human organ transplant patient management. Other therapies have not proceeded to human translation due to failure in NHP testing, arguably sparing humans the futility and risk of such testing. The NHP transplant models are ethically necessary for drug development in this field and provide the closest analogue to human transplant patients available. The refinement of this resource with respect to colony MHC typing, reagent and assay development, and availability to the research community has greatly enhanced knowledge about transplant immunology and drug development.


Assuntos
Transplante de Órgãos , Imunologia de Transplantes , Animais , Pesquisa Biomédica , Modelos Animais , Primatas
18.
Plast Reconstr Surg ; 143(4): 880e-886e, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30921156

RESUMO

Since the 1960s, skin has been considered to be the most allogenic tissue in humans. This tenet has remained unquestioned in the reconstructive transplant arena, which has led to skin serving as the sole monitor for early rejection in vascularized composite allotransplantation. In this article, the authors question the validity of this belief. The authors' hypothesis is that skin is not always an accurate monitor of rejection in the deep tissues, thus questioning the positive and negative predictive value of the punch biopsy for suspected vascularized composite allotransplantation rejection. A search was carried out identifying vascularized composite allotransplantation publications where the allogenicity of transplanted skin was evaluated. Eighteen publications claimed skin was found to be the most allogenic tissue in humans, justifying its use as a superior monitor for rejection. Eight publications demonstrated skin to be a poor monitor of rejection deeper to the skin. Two vascularized composite allotransplantation animal studies reported skin rejecting simultaneously with the deeper tissues. Finally, three publications discussed a skin and kidney allograft, transplanted simultaneously, indicating skin allogenicity was equivalent to the that of the kidney allograft. Much of the literature in human vascularized composite allotransplantation claims skin to be an excellent monitor of the deep tissues. The conclusion from this study is that skin does not always function as a good monitor for what could be rejecting in the deep tissues. The authors believe continued research is necessary to focus on expanding novel monitoring techniques and technologies to accurately diagnose vascularized composite allotransplantation rejection without tissue destruction.


Assuntos
Aloenxertos Compostos/fisiologia , Fenômenos Fisiológicos da Pele , Animais , Aloenxertos Compostos/imunologia , Rejeição de Enxerto/fisiopatologia , Humanos , Modelos Animais , Terminologia como Assunto , Imunologia de Transplantes/fisiologia , Alotransplante de Tecidos Compostos Vascularizados/tendências
19.
Cell Prolif ; 52(3): e12599, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30912260

RESUMO

Sertoli cells (SeC) are responsible for the immunoprivileged status of the testis thanks to which allogeneic or xenogeneic engraftments can survive without pharmacological immune suppression if co-injected with SeC. This peculiar ability of SeC is dependent on secretion of a plethora of factors including maturation factors, hormones, growth factors, cytokines and immunomodulatory factors. The anti-inflammatory and trophic properties of SeC have been largely exploited in several experimental models of diseases, diabetes being the most studied. Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive pathology in which lack of functional dystrophin leads to progressive muscle degeneration culminating in loss of locomotion and premature death. Despite a huge effort to find a cure, DMD patients are currently treated with anti-inflammatory steroids. Recently, encapsulated porcine SeC (MC-SeC) have been injected ip in the absence of immunosuppression in an animal model of DMD resulting in reduction of muscle inflammation and amelioration of muscle morphology and functionality, thus opening an additional avenue in the treatment of DMD. The novel protocol is endowed with the advantage of being potentially applicable to all the cohort of DMD patients regardless of the mutation. This mini-review addresses several issues linked to the possible use of MC-SeC injected ip in dystrophic people.


Assuntos
Transplante de Células/métodos , Distrofia Muscular de Duchenne/terapia , Células de Sertoli/transplante , Animais , Modelos Animais de Doenças , Xenoenxertos , Humanos , Privilégio Imunológico , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos mdx , Distrofia Muscular Animal/patologia , Distrofia Muscular Animal/fisiopatologia , Distrofia Muscular Animal/terapia , Distrofia Muscular de Duchenne/patologia , Distrofia Muscular de Duchenne/fisiopatologia , Células de Sertoli/imunologia , Suínos , Imunologia de Transplantes
20.
Hum Immunol ; 80(6): 385-392, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30836129

RESUMO

Vascularized composite allotransplantation (VCA) has emerged as the most recent field of transplantation to offer an alternative treatment for those patients that have failed or are not suitable candidates for conventional therapy. Most of the current clinical experience in this field is with recipients of skin containing grafts such as the face, upper extremity and abdominal wall transplants. Like solid organ recipients, VCA recipients require lifelong systematic immunosuppression to maintain their grafts. To date, the most successful immunosuppressant regimens are calcineurin inhibitor based and have been targeted to the control of T cells. While these regimens have resulted in excellent short term graft survival in solid organ transplantation, achieving significant improvements in long term survival has been more challenging. The reasons are multi-factorial, but a role for B cells and humoral immunity has been proposed. Antibody mediated rejection leading to chronic rejection has been cited as the leading cause of renal graft loss. While the number of VCA transplants performed is still small, evidence to date suggests that antibody mediated rejection may occur less frequently than seen in solid organ transplants. Here we will discuss the role of B cell immunity in solid organ transplantation as it pertains and contrasts to the field of VCA and present some examples of possible sequela of B cell immunity in a series of hand transplant recipients.


Assuntos
Linfócitos B/imunologia , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Imunidade Humoral , Alotransplante de Tecidos Compostos Vascularizados , Animais , Transplante de Mão , Humanos , Tolerância Imunológica , Imunologia de Transplantes
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