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1.
Stud Health Technol Inform ; 270: 272-276, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32570389

RESUMO

After kidney transplantation graft rejection must be prevented. Therefore, a multitude of parameters of the patient is observed pre- and postoperatively. To support this process, the Screen Reject research project is developing a data warehouse optimized for kidney rejection diagnostics. In the course of this project it was discovered that important information are only available in form of free texts instead of structured data and can therefore not be processed by standard ETL tools, which is necessary to establish a digital expert system for rejection diagnostics. Due to this reason, data integration has been improved by a combination of methods from natural language processing and methods from image processing. Based on state-of-the-art data warehousing technologies (Microsoft SSIS), a generic data integration tool has been developed. The tool was evaluated by extracting Banff-classification from 218 pathology reports and extracting HLA mismatches from about 1700 PDF files, both written in german language.


Assuntos
Data Warehousing , Transplante de Rim , Rejeição de Enxerto , Humanos , Armazenamento e Recuperação da Informação , Rim , Processamento de Linguagem Natural
2.
Medicine (Baltimore) ; 99(23): e20522, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502003

RESUMO

Data on protocol biopsies (PBs) after pediatric kidney transplantation are rare.We evaluated 6-month post-transplantation renal function in 86 children after PB as observational study. Patients were divided into 3 groups:Glomerular filtration rate (GFR) and delta GFR were determined.PBs 6 months post-kidney transplantation did not influence the clinical course in stable pediatric patients and are therefore of questionable value. Decreased kidney function may however be stabilized by therapeutic intervention according to results of PB.


Assuntos
Biópsia/métodos , Transplante de Rim/efeitos adversos , Adolescente , Biópsia/estatística & dados numéricos , Criança , Pré-Escolar , Protocolos Clínicos , Feminino , Taxa de Filtração Glomerular/fisiologia , Rejeição de Enxerto/patologia , Humanos , Rim/patologia , Transplante de Rim/métodos , Masculino , Pediatria/métodos , Pediatria/estatística & dados numéricos
4.
Rev Assoc Med Bras (1992) ; 66(3): 353-358, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32520157

RESUMO

OBJECTIVE: Melatonin has anti-inflammatory and antioxidant properties that can influence tissue growth and apoptosis. This aspect may influence the success of organ transplantation. To evaluate the relationship between melatonin and organ transplantation. METHODS: A systematic review was performed in PubMed databases using the search terms: "melatonin physiology" or "melatonin therapy" and "transplant pharmacology" or "transplant physiology" or "transplant therapy" or "Transplant therapy". Experiments on the organs of the reproductive system were not included. After analysis, five articles were selected after reading the title and abstract of 50 manuscripts. The works were divided into two aspects: a) analysis of the influence of the organ transplantation procedure on melatonin production; b) action of melatonin on organ transplantation. RESULTS: The cardiac transplantation surgical procedure, immunosuppression, and graft did not influence melatonin secretion in rodents, but there was a significant reduction of melatonin in the renal transplantation procedure in patients with renal insufficiency. Melatonin administration in experimental models decreased rejection and improved transplant success. CONCLUSION: Studies show that melatonin can reduce organ and species dependence, and the use of melatonin decreases graft rejection.


Assuntos
Antioxidantes/administração & dosagem , Rejeição de Enxerto/prevenção & controle , Melatonina/administração & dosagem , Transplante de Órgãos , Animais , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Coração , Humanos , Imunossupressão , Transplante de Rim , Melatonina/fisiologia , Ratos
6.
Medicine (Baltimore) ; 99(20): e20205, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443344

RESUMO

BACKGROUND: Autoimmune liver disease (ALD) is a chronic liver disease caused by immune dysfunction in the body. However, no causative or curative medical treatment with proven efficacy exists to cure ALDs, and liver transplantation (LT) remains the only effective treatment available. However, the problem of recurrence of ALDs (rALDs) still remains after LT, which seriously affects the survival rate of the patients. Therefore, clinicians need to be aware of the risk factors affecting rALDs after LT. Therefore, this meta-analysis aims to define the risk factors for rALDs, which include the recurrence of primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. METHODS: A systematic search in Pubmed, Embase, Cochrane library and Web of Science databases was performed from 1980 to 2019. The inclusion criteria were risk factors for developing rALDs after LT. However, case series, case reports, reviews, meta-analysis and studies only including human immunodeficiency virus cases, children, and pregnant patients were excluded. RESULTS: The electronic database search yielded 1728 results. Sixty-three retrospective cohort studies met the inclusion criteria and 13 were included in the meta-analysis. The final cohort included 5077 patients, and among them, 21.96% developed rALDs. Colectomy before LT, HR 0.59 (95% confidence interval [CI]: 0.37-0.96), cholangiocarcinoma, HR 3.42 (95% CI: 1.88-6.21), multiple episodes of acute cellular rejection, HR 2.07 (95% CI: 1.27-3.37), model for end-stage liver disease score, HR 1.05 (95% CI: 1.02-1.08), use of mycophenolate mofetil, HR 1.46 (95% CI: 1.00-2.12) and the use of cyclosporin A, HR 0.69 (95% CI: 0.49-0.97) were associated with the risk of rprimary sclerosing cholangitis. In addition, the use of tacrolimus, HR 1.73 (95% CI: 1.00-2.99) and cyclosporin A, HR 0.59 (95% CI: 0.39-0.88) were associated with the risk of rALD. CONCLUSIONS: Multiple risk factors for rALDs were identified, such as colectomy before LT, cholangiocacinoma, multiple episodes of acute cellular rejection, model for end-stage liver disease score, and especially the use of mycophenolate mofetil, cyclosporin A and tacrolimus.


Assuntos
Colangite Esclerosante/etiologia , Hepatopatias/imunologia , Transplante de Fígado/efeitos adversos , Adulto , Inibidores de Calcineurina/efeitos adversos , Colangiocarcinoma/complicações , Colangite Esclerosante/induzido quimicamente , Colangite Esclerosante/epidemiologia , Colectomia/efeitos adversos , Colectomia/estatística & dados numéricos , Ciclosporina/efeitos adversos , Doença Hepática Terminal/complicações , Inibidores Enzimáticos/efeitos adversos , Feminino , Rejeição de Enxerto/complicações , Hepatite Autoimune/complicações , Hepatite Autoimune/epidemiologia , Humanos , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/epidemiologia , Hepatopatias/etiologia , Hepatopatias/mortalidade , Hepatopatias/patologia , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Recidiva , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Tacrolimo/efeitos adversos
7.
Scand J Immunol ; 92(2): e12912, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32458431

RESUMO

Immune processes in liver transplantation remain poorly understood. Acute allograft rejection in liver transplantation is a kind of T cell-mediated inflammatory disease accompanied by inflammatory cell infiltration. However, the effect of acute allograft rejection on the immunological characteristics of TCRs in peripheral blood mononuclear cell is unknown. In this study, we characterized the pattern of the human T cell receptor beta chain (TRB) and immunoglobulin heavy chain (IGH) complementarity-determining region 3 (CDR3) repertoires via high-throughput sequencing in 11 acute allograft rejection (AG) cases, 23 patients with stable allograft liver function (ST) who had liver transplantation performed and 20 healthy controls (HC). The diversity of TRB-CDR3 was significantly reduced in the AG group compared with the ST group and healthy controls (HC). The CDR3 and N-addition length distribution were not significantly different between the AG and ST groups. However, N-addition length distribution was significantly changed compared to HC. It seemed that AG used more short N-additions and healthy people used more long N-additions in TRB-CDR3 repertoire. Our findings suggested that the TRB-CDR3 region of AG had distinctive V gene use compared with that of HC. The characteristics of ST seemed to be in between those of AG and HC although the difference is not significant. Cluster analysis showed that the TRB repertoire could not effectively distinguish AG from ST. This research might give to a better understanding of the immune process of liver transplantation.


Assuntos
Regiões Determinantes de Complementaridade/imunologia , Rejeição de Enxerto/imunologia , Cadeias Pesadas de Imunoglobulinas/imunologia , Transplante de Fígado , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Adulto , Regiões Determinantes de Complementaridade/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T alfa-beta/genética
8.
Kidney Int ; 97(6): 1083-1088, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32354634

RESUMO

The outcome of SARS-CoV2 infection in patients who have received a kidney allograft and are being treated with immunosuppression is unclear. We describe 20 kidney transplant recipients (median age 59 years [inter quartile range 51-64 years], median age of transplant 13 years [9-20 years], baseline eGFR 36.5 [23-47.5]) with SARS-CoV2 induced pneumonia. At admission, all had immunosuppression withdrawn and were started on methylprednisolone 16 mg/day, all but one was commenced on antiviral therapy and hydroxychloroquine with doses adjusted for kidney function. At baseline, all patients presented fever but only one complained of difficulty in breathing. Half of patients showed chest radiographic evidence of bilateral infiltrates while the other half showed unilateral changes or no infiltrates. During a median follow-up of seven days, 87% experienced a radiological progression and among those 73% required escalation of oxygen therapy. Six patients developed acute kidney injury with one requiring hemodialysis. Six of 12 patients were treated with tocilizumab, a humanized monoclonal antibody to the IL-6 receptor. Overall, five kidney transplant recipients died after a median period of 15 days [15-19] from symptom onset. These preliminary findings describe a rapid clinical deterioration associated with chest radiographic deterioration and escalating oxygen requirement in renal transplant recipients with SARS-Cov2 pneumonia. Thus, in this limited cohort of long-term kidney transplant patients, SARS-CoV-2 induced pneumonia is characterized by high risk of progression and significant mortality.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/mortalidade , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Pneumonia Viral/mortalidade , Anticorpos Monoclonais Humanizados/efeitos adversos , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Progressão da Doença , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Itália/epidemiologia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Oxigenoterapia/instrumentação , Oxigenoterapia/estatística & dados numéricos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Prognóstico , Transplantados/estatística & dados numéricos , Resultado do Tratamento
9.
Kidney Int ; 97(6): 1076-1082, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32354637

RESUMO

By 21 March 2020 infections related to the novel coronavirus SARS-CoV-2 had affected people from 177 countries and caused 11,252 reported deaths worldwide. Little is known about risk, presentation and outcomes of SARS-CoV-2 (COVID-19) infection in kidney transplantation recipients, who may be at high-risk due to long-term immunosuppression, comorbidity and residual chronic kidney disease. Whilst COVID-19 is predominantly a respiratory disease, in severe cases it can cause kidney and multi-organ failure. It is unknown if immunocompromised hosts are at higher risk of more severe systemic disease. Therefore, we report on seven cases of COVID-19 in kidney transplant recipients (median age 54 (range 45-69), three females, from a cohort of 2082 managed transplant follow-up patients) over a six-week period in three south London hospitals. Two of seven patients presented within three months of transplantation. Overall, two were managed on an out-patient basis, but the remaining five required hospital admission, four in intensive care units. All patients displayed respiratory symptoms and fever. Other common clinical features included hypoxia, chest crepitation, lymphopenia and high C-reactive protein. Very high D dimer, ferritin and troponin levels occurred in severe cases and likely prognostic. Immunosuppression was modified in six of seven patients. Three patients with severe disease were diabetic. During a three week follow up one patient recovered, and one patient died. Thus, our findings suggest COVID-19 infection in kidney transplant patients may be severe, requiring intensive care admission. The symptoms are predominantly respiratory and associated with fever. Most patients had their immunosuppression reduced and were treated with supportive therapy.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Febre/epidemiologia , Imunossupressão/efeitos adversos , Transplante de Rim/efeitos adversos , Pneumonia Viral/epidemiologia , Idoso , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Feminino , Febre/diagnóstico , Febre/imunologia , Febre/virologia , Seguimentos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Hospedeiro Imunocomprometido/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Índice de Gravidade de Doença , Transplantados/estatística & dados numéricos
10.
Science ; 368(6495): 1122-1127, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32381589

RESUMO

Immunological memory specific to previously encountered antigens is a cardinal feature of adaptive lymphoid cells. However, it is unknown whether innate myeloid cells retain memory of prior antigenic stimulation and respond to it more vigorously on subsequent encounters. In this work, we show that murine monocytes and macrophages acquire memory specific to major histocompatibility complex I (MHC-I) antigens, and we identify A-type paired immunoglobulin-like receptors (PIR-As) as the MHC-I receptors necessary for the memory response. We demonstrate that deleting PIR-A in the recipient or blocking PIR-A binding to donor MHC-I molecules blocks memory and attenuates kidney and heart allograft rejection. Thus, innate myeloid cells acquire alloantigen-specific memory that can be targeted to improve transplant outcomes.


Assuntos
Rejeição de Enxerto/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Imunidade Inata , Memória Imunológica , Macrófagos/imunologia , Monócitos/imunologia , Receptores Imunológicos/fisiologia , Animais , Deleção de Genes , Rejeição de Enxerto/genética , Transplante de Coração , Transplante de Rim , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Mutantes , Receptores Imunológicos/genética
11.
J Korean Med Sci ; 35(20): e166, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32449324

RESUMO

BACKGROUND: Post-transplant cancer (PTC) is a critical complication after kidney transplantation. However, whether successfully cured PTC affects the long-term graft outcome remains unclear. METHODS: We retrospectively reviewed 1,629 kidney transplant recipients from 1995 to 2017 after excluding patients with post-transplant hematologic or advanced non-curable cancers and who underwent allograft nephrectomy because of cancer. Cured PTCs were defined as cancers treated with curative methods and/or adjuvant therapy without recurrence during ≥ 2 years. Propensity score matching was performed to match cured PTC patients with cancer-naïve patients (i.e., non-PTC group). RESULTS: During the median period of 7 years (maximum, 23 years), 70 patients (4.3%) had cured PTCs. The PTC group showed significantly higher risks of death-censored graft failure (adjusted hazard ratio [HR], 2.56 [1.05-6.23]), class II donor-specific antibodies (adjusted HRs, 3.37 [1.30-8.71]), estimated glomerular filtration rate < 30 mL/min/1.73 m² (adjusted HR, 2.68 [1.43-5.02]) and random urine protein/creatinine ratio > 1 g (adjusted HR, 3.61 [1.92-6.79]) compared to non-PTC group. However, the risk of mortality was not different between the PTC and non-PTC groups. According to the cancer type, only urogenital cancer had a significant association with graft failure (adjusted HR, 4.26 [1.19-15.22]) and the gastrointestinal cancer showed elevated risk of T cell mediated rejection compared to non-PTC (adjusted HR, 20.44 [6.02-69.39]). CONCLUSION: Appropriate monitoring of graft function is necessary in patients with cured PTCs.


Assuntos
Rejeição de Enxerto , Transplante de Rim , Insuficiência Renal Crônica/cirurgia , Adulto , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Insuficiência Renal Crônica/complicações , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo , Resultado do Tratamento
12.
Biol Blood Marrow Transplant ; 26(7): e161-e166, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32389803

RESUMO

With the COVID-19 pandemic and the ensuing barriers to the collection and transport of donor cells, it is often necessary to collect and cryopreserve grafts before initiation of transplantation conditioning. The effect on transplantation outcomes in nonmalignant disease is unknown. This analysis examined the effect of cryopreservation of related and unrelated donor grafts for transplantation for severe aplastic anemia in the United States during 2013 to 2019. Included are 52 recipients of cryopreserved grafts who were matched for age, donor type, and graft type to 194 recipients who received noncryopreserved grafts. Marginal Cox regression models were built to study the effect of cryopreservation and other risk factors associated with outcomes. We recorded higher 1-year rates of graft failure (hazard ratio [HR], 2.26; 95% confidence interval, 1.17 to 4.35; P = .01) and of 1-year overall mortality (HR, 3.13; 95% CI, 1.60 to 6.11; P = .0008) after transplantation of cryopreserved compared with noncryopreserved grafts, with adjustment for sex, performance score, comorbidity, cytomegalovirus serostatus, and ABO blood group match. The incidence of acute and chronic graft-versus-host disease did not differ between the 2 groups. Adjusted probabilities of 1-year survival were 73% (95% CI, 60% to 84%) in the cryopreserved graft group and 91% (95% CI, 86% to 94%) in the noncryopreserved graft group. These data support the use of noncryopreserved grafts whenever possible in patients with severe aplastic anemia.


Assuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea/métodos , Infecções por Coronavirus/epidemiologia , Criopreservação/métodos , Rejeição de Enxerto/patologia , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco de Sangue Periférico/métodos , Pneumonia Viral/epidemiologia , Doença Aguda , Adolescente , Adulto , Idoso , Anemia Aplástica/imunologia , Anemia Aplástica/mortalidade , Anemia Aplástica/patologia , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/mortalidade , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Irmãos , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Estados Unidos/epidemiologia , Doadores não Relacionados
13.
Lancet ; 395(10237): 1627-1639, 2020 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-32446407

RESUMO

BACKGROUND: Use of cell-based medicinal products (CBMPs) represents a state-of-the-art approach for reducing general immunosuppression in organ transplantation. We tested multiple regulatory CBMPs in kidney transplant trials to establish the safety of regulatory CBMPs when combined with reduced immunosuppressive treatment. METHODS: The ONE Study consisted of seven investigator-led, single-arm trials done internationally at eight hospitals in France, Germany, Italy, the UK, and the USA (60 week follow-up). Included patients were living-donor kidney transplant recipients aged 18 years and older. The reference group trial (RGT) was a standard-of-care group given basiliximab, tapered steroids, mycophenolate mofetil, and tacrolimus. Six non-randomised phase 1/2A cell therapy group (CTG) trials were pooled and analysed, in which patients received one of six CBMPs containing regulatory T cells, dendritic cells, or macrophages; patient selection and immunosuppression mirrored the RGT, except basiliximab induction was substituted with CBMPs and mycophenolate mofetil tapering was allowed. None of the trials were randomised and none of the individuals involved were masked. The primary endpoint was biopsy-confirmed acute rejection (BCAR) within 60 weeks after transplantation; adverse event coding was centralised. The RTG and CTG trials are registered with ClinicalTrials.gov, NCT01656135, NCT02252055, NCT02085629, NCT02244801, NCT02371434, NCT02129881, and NCT02091232. FINDINGS: The seven trials took place between Dec 11, 2012, and Nov 14, 2018. Of 782 patients assessed for eligibility, 130 (17%) patients were enrolled and 104 were treated and included in the analysis. The 66 patients who were treated in the RGT were 73% male and had a median age of 47 years. The 38 patients who were treated across six CTG trials were 71% male and had a median age of 45 years. Standard-of-care immunosuppression in the recipients in the RGT resulted in a 12% BCAR rate (expected range 3·2-18·0). The overall BCAR rate for the six parallel CTG trials was 16%. 15 (40%) patients given CBMPs were successfully weaned from mycophenolate mofetil and maintained on tacrolimus monotherapy. Combined adverse event data and BCAR episodes from all six CTG trials revealed no safety concerns when compared with the RGT. Fewer episodes of infections were registered in CTG trials versus the RGT. INTERPRETATION: Regulatory cell therapy is achievable and safe in living-donor kidney transplant recipients, and is associated with fewer infectious complications, but similar rejection rates in the first year. Therefore, immune cell therapy is a potentially useful therapeutic approach in recipients of kidney transplant to minimise the burden of general immunosuppression. FUNDING: The 7th EU Framework Programme.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Rejeição de Enxerto/prevenção & controle , Imunossupressão/métodos , Imunossupressores/uso terapêutico , Transplante de Rim , Terapia Baseada em Transplante de Células e Tecidos/efeitos adversos , Células Dendríticas/imunologia , Rejeição de Enxerto/imunologia , Humanos , Imunossupressão/efeitos adversos , Macrófagos/imunologia , Linfócitos T Reguladores/imunologia
15.
PLoS One ; 15(4): e0231646, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32343692

RESUMO

Transplant glomerulopathy (TG), a morphological lesion associated with confluent mechanisms of endothelial injury of renal allografts, may provide a viable predictor of graft failure. This systematic literature review and meta-analysis were performed according to the PRISMA statement to examine evidence describing the association between TG and graft loss or failure and time to these events. The literature review was conducted using the Scopus, EBSCO, and Cochrane Library search engines. Hazard ratios, median survival times, and 95% confidence intervals (CIs) were estimated to evaluate graft survival in the total population and prespecified subgroups. Meta-regression analysis assessed heterogeneity. Twenty-one publications comprising 6,783 patients were eligible for data extraction and inclusion in the meta-analysis. Studies were highly heterogeneous (I2 = 67.3%). The combined hazard ratio of graft loss or failure from random-effects meta-analysis was 3.11 (95% CI 2.44-3.96) in patients with TG compared with those without. Median graft survival in patients with TG was 3.25 (95% CI 0.94-11.21) years-15 years shorter than in those without TG (18.82 [95% CI 10.03-35.32] years). The effect of time from transplantation to biopsy on graft outcomes did not reach statistical significance (p = 0.116). TG was associated with a threefold increase in the risk of graft loss or failure and a 15-year loss in graft survival, indicating viability as a surrogate measure for both clinical practice and studies designed to prevent or reverse antibody-mediated rejection.


Assuntos
Glomerulonefrite/epidemiologia , Rejeição de Enxerto/epidemiologia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Feminino , Humanos , Transplante de Rim/estatística & dados numéricos , Masculino
16.
Nature ; 580(7801): 130-135, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32238926

RESUMO

Caspase-dependent apoptosis accounts for approximately 90% of homeostatic cell turnover in the body1, and regulates inflammation, cell proliferation, and tissue regeneration2-4. How apoptotic cells mediate such diverse effects is not fully understood. Here we profiled the apoptotic metabolite secretome and determined its effects on the tissue neighbourhood. We show that apoptotic lymphocytes and macrophages release specific metabolites, while retaining their membrane integrity. A subset of these metabolites is also shared across different primary cells and cell lines after the induction of apoptosis by different stimuli. Mechanistically, the apoptotic metabolite secretome is not simply due to passive emptying of cellular contents and instead is a regulated process. Caspase-mediated opening of pannexin 1 channels at the plasma membrane facilitated the release of a select subset of metabolites. In addition, certain metabolic pathways continued to remain active during apoptosis, with the release of only select metabolites from a given pathway. Functionally, the apoptotic metabolite secretome induced specific gene programs in healthy neighbouring cells, including suppression of inflammation, cell proliferation, and wound healing. Furthermore, a cocktail of apoptotic metabolites reduced disease severity in mouse models of inflammatory arthritis and lung-graft rejection. These data advance the concept that apoptotic cells are not inert cells waiting for removal, but instead release metabolites as 'good-bye' signals to actively modulate outcomes in tissues.


Assuntos
Apoptose/fisiologia , Microambiente Celular , Sistemas do Segundo Mensageiro/fisiologia , Animais , Artrite , Caspases/metabolismo , Linhagem Celular , Proliferação de Células/genética , Sobrevivência Celular/genética , Conexinas/metabolismo , Modelos Animais de Doenças , Rejeição de Enxerto , Humanos , Inflamação/genética , Transplante de Pulmão , Linfócitos/enzimologia , Linfócitos/metabolismo , Macrófagos/enzimologia , Macrófagos/metabolismo , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Fagócitos/metabolismo , Cicatrização/genética
17.
Methodist Debakey Cardiovasc J ; 16(1): 43-49, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32280417

RESUMO

Cardiogenic shock (CS) is a complex syndrome of end-organ hypoperfusion that requires timely and thorough decision making. While many pathophysiologic and technical principles have been delineated in this issue, the purpose of this case-based report is to reflect upon some of these principles in the context of real-life scenarios. Given the obvious lacuna of evidence-based recommendations in CS, the authors provide a rationale for their decision-making process. The first case is a young post-heart-transplant patient with graft failure who was in a state of biventricular failure and restrictive physiology and required acute mechanical circulatory support (MCS). The second case is a patient who suffered a mechanical complication after experiencing an acute myocardial infarction that required MCS.


Assuntos
Rejeição de Enxerto/etiologia , Insuficiência Cardíaca/fisiopatologia , Transplante de Coração/efeitos adversos , Modelos Cardiovasculares , Infarto do Miocárdio/complicações , Choque Cardiogênico/fisiopatologia , Função Ventricular Esquerda , Função Ventricular Direita , Pressão Ventricular , Idoso , Cardiotônicos/uso terapêutico , Oxigenação por Membrana Extracorpórea , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/fisiopatologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Coração Auxiliar , Humanos , Balão Intra-Aórtico/instrumentação , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia , Recuperação de Função Fisiológica , Fatores de Risco , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Volume Sistólico , Resultado do Tratamento , Adulto Jovem
18.
Zhonghua Shao Shang Za Zhi ; 36(3): 234-243, 2020 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-32241050

RESUMO

Objective: To explore the effects and mechanism of interleukin-17 (IL-17)-modified mouse bone marrow mesenchymal stem cells (BMSCs) on the allogeneic skin transplantation in mice. Methods: (1) The femur, tibia, and humerus were isolated from five BALB/c mice (all female, aged 4 to 8 weeks, the same gender and age below) after sacrifice. BMSCs were isolated, purified, and cultured by whole bone marrow density gradient centrifugation combined with adherent separation method. The third passage of cells was used for morphological observation and identification of adipogenic and osteogenic differentiation. The fourth passage of cells was used for identification of the expression of stem cell surface markers. The third to sixth passages of BMSCs were pretreated with mouse recombinant IL-17 at a final mass concentration of 50 ng/mL for 5 days, and then were harvested for morphological observation. After being labeled with carbocyanine fluorescent dye (CM-Dil), IL-17-pretreated BMSCs and IL-17-unpretreated BMSCs were obtained for morphological observation and the labeling rates were calculated. (2) Forty-five C57BL/6J mice were divided into phosphate buffer solution (PBS) control group (n=13), BMSCs alone group (n=16), and BMSCs+ IL-17 group (n=16) according to the random number table. One day before the skin transplantation of mice, 0.1 mL BMSCs (5×10(6) cells/mL) without CM-Dil labeling were injected to the 13 mice in BMSCs alone group through the tail vein, and 0.1 mL BMSCs (5×10(6) cells/mL) labeled with CM-Dil were injected to the other 3 mice in BMSCs alone group through the tail vein. IL-17-pretreated BMSCs (5×10(6) cells/mL) without CM-Dil labeling in the volume of 0.1 mL were injected to the 13 mice in BMSCs+ IL-17 group through the tail vein, and 0.1 mL IL-17-pretreated BMSCs (5×10(6) cells/mL) labeled with CM-Dil were injected to the other 3 mice in BMSCs+ IL-17 group through the tail vein. PBS in the volume of 0.1 mL was injected to the 13 mice in PBS control group through the tail vein. Forty-five BALB/c mice were used as donors, and forty-five treated C57BL/6J mice in the 3 groups were used as recipients to establish a back-to-back full-thickness skin transplantation model. On the 2nd day after transplantation, the same number of corresponding cells and the equal amount of PBS were injected to the recipient mice of each group again. On the 7th day after transplantation, three mice injected with CM-Dil-labeled BMSCs in BMSCs alone group and three mice injected with CM-Dil-labeled IL-17-pretreated BMSCs in BMSCs+ IL-17 group were sacrificed by cervical dislocation to track the CM-Dil-labeled BMSCs by fluorescence microscope, which was counted. After the dressing removal on the 6th day post transplantation, 7 mice were selected respectively from 13 mice in BMSCs alone group injected with BMSCs without CM-Dil-labeling, 13 mice in BMSCs+ IL-17 group injected with IL-17-pretreated BMSCs without CM-Dil-labeling, and 13 mice in PBS control group, respectively, to record the skin graft survival time. On the 8th day post transplantation, three of the remaining six mice in the three groups were taken for general observation of the grafted skin, serum levels of interferon-γ, IL-10, and transforming growth factor ß (TGF-ß) by enzyme-linked immunosorbent assay method, the percentage of CD4(+) CD25(+) forkhead/winged helix transcription factor p3 (Foxp3)(+) regulatory T cells (Tregs) in spleen by flow cytometer, and the histopathological observation of the grafted skin by hematoxylin eosin staining. The rest three mice in each group were also taken for histopathological observation as above on the 14th day post transplantation. Data were statistically analysed with independent sample t test, one-way analysis of variance, and least significant difference test. Results: (1) There were no significant differences in the morphology and size between IL-17-pretreated BMSCs and IL-17-unpretreated BMSCs on culture day 5. (2) After CM-Dil labeling, BMSCs and IL-17-pretreated BMSCs grew well, and the labeling rate was almost 100%. (3) On the 7th day post transplantation, there were 6.2±2.6 CM-Dil-labeled BMSCs per 100 fold visual field in the skin and adjacent subcutaneous tissue of mice in BMSCs alone group, which were significantly fewer than the 15.0±5.3 CM-Dil-labeled IL-17-pretreated BMSCs per 100 fold visual field in BMSCs+ IL-17 group (t=-2.962, P<0.05). (4) The skin graft survival time of mice in BMSCs alone group and BMSCs+ IL-17 group was (13.3±1.2) and (17.0±1.5) days respectively, significantly longer than (8.7±0.8) days in PBS control group (P<0.01), and the skin graft survival time of mice in BMSCs+ IL-17 group was significantly longer than that in BMSCs alone group (P<0.01). (5) On the 8th day post transplantation, most of the skin grafts of mice in PBS control group was black, scabby, and necrotic. Most of the skin grafts of mice in BMSCs alone group survived well, while all the skin grafts of mice in BMSCs+ IL-17 group survived well. (6) On the 8th day post transplantation, compared with those of PBS control group, the serum levels of IL-10 and TGF-ß of mice in BMSCs alone group and BMSCs+ IL-17 group were significantly higher (P<0.01), and the serum level of interferon-γ was significantly lower (P<0.01). Compared with those of BMSCs alone group, the serum levels of IL-10 and TGF-ß of mice in BMSCs+ IL-17 group were significantly higher (P<0.01), and the serum level of interferon-γ was significantly lower (P<0.01). (7) On the 8th day post transplantation, the percentages of CD4(+) CD25(+) Foxp3(+) Treg in spleen of mice in BMSCs alone group and BMSCs+ IL-17 group were significantly higher than the percentage of PBS control group (P<0.01), and the percentage of CD4(+) CD25(+) Foxp3(+) Treg in spleen of mice in BMSCs+ IL-17 group was significantly higher than that of BMSCs alone group (P<0.01). (8) On the 8th day post transplantation, infiltration of a large number of inflammatory cells and necrosis of epidermis and dermis were found in the skin grafts of mice in PBS control group; focal infiltration of inflammatory cells and slight epidermal degeneration were found in the skin grafts of mice in BMSCs alone group; the skin appendages of the skin grafts of mice in BMSCs+ IL-17 group survived well with angiogenesis. On the 14th day post transplantation, the skin grafts of mice in BMSCs alone group showed extensive infiltration of inflammatory cells, severe epidermal degeneration and focal necrosis; the skin grafts of mice in BMSCs+ IL-17 group showed focal infiltration of inflammatory cells and slight epidermal degeneration; the skin grafts of mice in PBS control group were completely necrotic. Conclusions: IL-17 can reduce the immune rejection in allogeneic skin grafting and prolong the survival time of mouse skin grafts by improving mice BMSCs' capabilities to induce immune tolerance and enhancing the homing ability of BMSCs.


Assuntos
Células da Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Transplante de Pele , Animais , Feminino , Rejeição de Enxerto , Interleucina-17 , Células-Tronco Mesenquimais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Osteogênese , Distribuição Aleatória
19.
Adv Exp Med Biol ; 1244: 287-293, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32301023

RESUMO

With the increasing use of immunotherapy, there has been an associated increased survival in many cancers but has also resulted in unregulated organ-specific toxicities. In this chapter, we discuss the renal toxicities associated with a checkpoint inhibitor (CPI) from the typical acute tubulointersitial nephritis to glomerulonephritis, their proposed mechanisms, and treatments. We also discuss the use of CPI and reactivation of preexisting auto-immune diseases and focus on renal cell cancer in setting of Chronic kidney disease (CKD). Transplant rejection in the setting of CPI use is yet to be further studied, and available data is presented in this chapter.


Assuntos
Rejeição de Enxerto/induzido quimicamente , Imunoterapia/efeitos adversos , Neoplasias/terapia , Nefrite/induzido quimicamente , Rejeição de Enxerto/imunologia , Humanos , Neoplasias/complicações , Neoplasias/imunologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/cirurgia
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