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4.
Transplantation ; 104(8): 1726-1737, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732853

RESUMO

BACKGROUND: De novo donor-specific antibodies (DSAs) are associated with antibody-mediated rejection (AMR) and allograft loss. Whether monitoring of de novo DSA (dnDSA) paired with systematic kidney biopsy should become routine remains to be established. METHODS: A retrospective multicentric study (9 French kidney transplant units of the Spiesser group) included patients without graft dysfunction biopsied because of the presence of dnDSA (One Lambda, mean fluorescence intensity [MFI], >1000). RESULTS: One hundred twenty-three patients (85 male/38 female; mean age, 49.5 ± 13.1 y old) were biopsied after the detection of a dnDSA, 65.3 months (median) after kidney transplantation. Graft function was stable within 3 months before biopsy (estimated glomerular filtration rate, 55.3 ± 18.9 mL/min/1.73 m). Fifty-one subclinical AMRs (sAMRs) (41.4%) were diagnosed, of which 32 (26%) active and 19 (15.5%) chronic active sAMR. Seventy-two biopsies revealed no AMR (58.5%). Predictive factors associated with the diagnosis of active sAMR were MFI of immunodominant DSA >4000, MFI of the sum of DSA >6300, age of the recipient <45 years old, and the absence of steroids at biopsy. The presence of proteinuria >200 mg/g was predictive of chronic active sAMR. The decrease of estimated glomerular filtration rate at 5 years post-biopsy was significantly higher in patients with acute sAMR (-25.2 ± 28.3 mL/min/1.73 m) and graft survival significantly lower. CONCLUSIONS: Performing a kidney graft biopsy for the occurrence of dnDSA without renal dysfunction leads to the diagnosis of a sAMR in over 40% of cases. Nevertheless, we did not observe any effect of standard treatment in acute sAMR.


Assuntos
Protocolos Clínicos , Rejeição de Enxerto/diagnóstico , Isoanticorpos/sangue , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Adulto , Aloenxertos , Biópsia , Feminino , Seguimentos , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/terapia , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Teste de Histocompatibilidade/normas , Humanos , Imunossupressores/uso terapêutico , Isoanticorpos/imunologia , Rim , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos , Resultado do Tratamento
5.
Nephrol Dial Transplant ; 35(7): 1250-1261, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32678882

RESUMO

BACKGROUND: Kidney graft recipients receiving immunosuppressive therapy may be at heightened risk for coronavirus disease 2019 (Covid-19) and adverse outcomes. It is therefore important to characterize the clinical course and outcome of Covid-19 in this population and identify safe therapeutic strategies. METHODS: We performed a retrospective chart review of 73 adult kidney graft recipients evaluated for Covid-19 from 13 March to 20 April 2020. Primary outcomes included recovery from symptoms, acute kidney injury, graft failure and case fatality rate. RESULTS: Of the 73 patients screened, 54 tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-39 with moderate to severe symptoms requiring hospital admission and 15 with mild symptoms managed in the ambulatory setting. Hospitalized patients were more likely to be male, of Hispanic ethnicity and to have cardiovascular disease. In the hospitalized group, tacrolimus dosage was reduced in 46% of patients and mycophenolate mofetil (MMF) therapy was stopped in 61% of patients. None of the ambulatory patients had tacrolimus reduction or discontinuation of MMF. Azithromycin or doxycycline was prescribed at a similar rate among hospitalized and ambulatory patients (38% versus 40%). Hydroxychloroquine was prescribed in 79% of hospitalized patients. Graft failure requiring hemodialysis occurred in 3 of 39 hospitalized patients (8%) and 7 patients died, resulting in a case fatality rate of 13% among Covid-19-positive patients and 18% among hospitalized Covid-19-positive patients. CONCLUSIONS: Data from our study suggest that a strategy of systematic triage to outpatient or inpatient care, early management of concurrent bacterial infections and judicious adjustment of immunosuppressive drugs rather than cessation is feasible in kidney transplant recipients with Covid-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Rejeição de Enxerto/terapia , Hidroxicloroquina/uso terapêutico , Imunossupressão/métodos , Transplante de Rim , Ácido Micofenólico/uso terapêutico , Pneumonia Viral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Antimaláricos/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Inibidores Enzimáticos/uso terapêutico , Feminino , Rejeição de Enxerto/complicações , Rejeição de Enxerto/epidemiologia , Humanos , Imunossupressores/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , Transplantados
7.
Am J Obstet Gynecol ; 223(2): 143-151, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32151611

RESUMO

Uterus transplantation is the only known potential treatment for absolute uterine factor infertility. It offers a unique setting for the investigation of immunologic adaptations of pregnancy in the context of the pharmacologic-induced tolerance of solid organ transplants, thus providing valuable insights into the early maternal-fetal interface. Until recently, all live births resulting from uterus transplantation involved living donors, with only 1 prior birth from a deceased donor. The Cleveland Clinic clinical trial of uterus transplantation opened in 2015. In 2017, a 35 year old woman with congenital absence of the uterus was matched to a 24 year old parous deceased brain-dead donor. Transplantation of the uterus was performed with vaginal anastomosis and vascular anastomoses bilaterally from internal iliac vessels of the donor to the external iliac vessels of the recipient. Induction and maintenance immunosuppression were achieved and subsequently modified in anticipation of pregnancy 6 months after transplant. Prior to planned embryo transfer, ectocervical biopsy revealed ulceration and a significant diffuse, plasma cell-rich mixed inflammatory cell infiltrate, with histology interpreted as grade 3 rejection suspicious for an antibody-mediated component. Aggressive immunosuppressive regimen targeting both cellular and humoral rejection was initiated. After 3 months of treatment, there was no histologic evidence of rejection, and after 3 months from complete clearance of rejection, an uneventful embryo transfer was performed and a pregnancy was established. At 21 weeks, central placenta previa with accreta was diagnosed. A healthy neonate was delivered by cesarean hysterectomy at 34 weeks' gestation. In summary, this paper highlights the first live birth in North America resulting from a deceased donor uterus transplant. This achievement underscores the capacity of the transplanted uterus to recover from a severe, prolonged rejection and yet produce a viable neonate. This is the first delivery from our ongoing clinical trial in uterus transplantation, including the first reported incidence of severe mixed cellular/humoral rejection as well as the first reported placenta accreta.


Assuntos
Cesárea , Rejeição de Enxerto/terapia , Transplante de Órgãos/efeitos adversos , Útero/transplante , Adulto , Feminino , Rejeição de Enxerto/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Recém-Nascido , Plasmaferese , Gravidez , Resultado da Gravidez , Resultado do Tratamento
8.
Transplantation ; 104(5): 911-922, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31895348

RESUMO

With the development of modern solid-phase assays to detect anti-HLA antibodies and a more precise histological classification, the diagnosis of antibody-mediated rejection (AMR) has become more common and is a major cause of kidney graft loss. Currently, there are no approved therapies and treatment guidelines are based on low-level evidence. The number of prospective randomized trials for the treatment of AMR is small, and the lack of an accepted common standard for care has been an impediment to the development of new therapies. To help alleviate this, The Transplantation Society convened a meeting of international experts to develop a consensus as to what is appropriate treatment for active and chronic active AMR. The aim was to reach a consensus for standard of care treatment against which new therapies could be evaluated. At the meeting, the underlying biology of AMR, the criteria for diagnosis, the clinical phenotypes, and outcomes were discussed. The evidence for different treatments was reviewed, and a consensus for what is acceptable standard of care for the treatment of active and chronic active AMR was presented. While it was agreed that the aims of treatment are to preserve renal function, reduce histological injury, and reduce the titer of donor-specific antibody, there was no conclusive evidence to support any specific therapy. As a result, the treatment recommendations are largely based on expert opinion. It is acknowledged that properly conducted and powered clinical trials of biologically plausible agents are urgently needed to improve patient outcomes.


Assuntos
Soro Antilinfocitário/uso terapêutico , Consenso , Rejeição de Enxerto/terapia , Imunossupressão/métodos , Isoanticorpos/uso terapêutico , Transplante de Rim , Sociedades Médicas , Rejeição de Enxerto/imunologia , Humanos , Doadores de Tecidos
9.
Transplantation ; 104(4): 700-707, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31815910

RESUMO

Noninvasive biomarkers are needed to monitor stable patients following kidney transplantation (KT), as subclinical rejection, currently detectable only with invasive surveillance biopsies, can lead to chronic rejection and graft loss. Several biomarkers have recently been developed to detect rejection in KT recipients, using different technologies as well as varying clinical monitoring strategies defined as "context of use (COU)." The various metrics utilized to evaluate the performance of each biomarker can also vary, depending on their intended COU. As the use of molecular biomarkers in transplantation represents a new era in patient management, it is important for clinicians to better understand the process by which the incremental value of each biomarkers is evaluated to determine its potential role in clinical practice. This process includes but is not limited to an assessment of clinical validity and utility, but to define these, the clinician must first appreciate the trajectory of a biomarker from bench to bedside as well as the regulatory and other requirements needed to navigate this course successfully. This overview summarizes this process, providing a framework that can be used by clinicians as a practical guide in general, and more specifically in the context of subclinical rejection following KT. In addition, we have reviewed available as well as promising biomarkers for this purpose in terms of the clinical need, COU, assessment of biomarker performance relevant to both the need and COU, assessment of biomarker benefits and risks relevant to the COU, and the evidentiary criteria of the biomarker relevant to the COU compared with the current standard of care. We also provide an insight into the path required to make biomarkers commercially available once they have been developed and validated so that they used by clinicians outside the research context in every day clinical practice.


Assuntos
Biomarcadores/metabolismo , Rejeição de Enxerto/diagnóstico , Transplante de Rim/efeitos adversos , Doenças Assintomáticas , Tomada de Decisão Clínica , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/terapia , Humanos , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Resultado do Tratamento
10.
Am J Kidney Dis ; 75(1): 138-143, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31515140

RESUMO

Improving precision in predicting alloreactivity is an important unmet need and may require individualized consideration of non-HLA antibodies. We report a 21-year-old man with kidney failure from immunoglobulin A nephropathy who met all traditional criteria for a "low-risk" transplant for immune memory. He was unsensitized and received a haplotype-matched living donor kidney transplant from his mother. There were no anti-HLA donor-specific antibodies and flow cross-match was negative. After immediate function, he developed delayed graft function on postoperative day 2. The transplant biopsy specimen was suggestive of antibody-mediated rejection and acute tubular injury with increased vimentin proximal tubular expression compared to the implantation biopsy specimen. He had a history of juvenile idiopathic arthritis, and non-HLA antibody screening demonstrated preformed anti-vimentin antibody. He was successfully treated with plasmapheresis, intravenous immunoglobulin, antithymocyte globulin, and methylprednisolone, with renal recovery. The follow-up biopsy specimen demonstrated decreased vimentin expression with decreased alloinflammation, and graft function remains stable at 1 year posttransplantation (estimated glomerular filtration rate, 62mL/min/1.73m2). We postulate that preformed anti-vimentin autoantibodies bound to vimentin expressed on apoptotic tubular epithelial cells induced by ischemia-reperfusion injury and to constitutively expressed vimentin on peritubular capillaries and podocytes. Our case is suggestive of the involvement of anti-vimentin antibody, for which the pathogenic epitopes may be exposed during ischemia-reperfusion injury.


Assuntos
Anticorpos/imunologia , Glomerulonefrite por IGA/cirurgia , Rejeição de Enxerto/imunologia , Falência Renal Crônica/cirurgia , Transplante de Rim , Vimentina/imunologia , Soro Antilinfocitário/uso terapêutico , Função Retardada do Enxerto/imunologia , Função Retardada do Enxerto/terapia , Glomerulonefrite por IGA/complicações , Glucocorticoides/uso terapêutico , Rejeição de Enxerto/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Falência Renal Crônica/etiologia , Masculino , Metilprednisolona/uso terapêutico , Plasmaferese , Adulto Jovem
11.
Expert Rev Clin Immunol ; 15(12): 1249-1262, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31721600

RESUMO

Introduction: For late stage organ failure patients, transplantation is the best option to increase life expectancy with a superior quality of life. Unfortunately, after transplantation many patients are at risk of cellular and antibody-mediated rejection (ABMR). The latter is initiated by donor specific antibodies (DSA) which depend on the actions of B cells, T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells that are present in the germinal center of lymphoid organs.Areas covered: In this overview paper, we discuss the biology and function of Tfh and Tfr cells in lymphoid tissues, transplanted organs and their circulating counterparts. We report on their relevance to alloimmunity and on the effects of immunosuppressive drugs on these immunocompetent cell populations.Expert opinion: Growing knowledge about the actions of Tfh and Tfr allows for a better understanding of the immunological mechanisms of ABMR after organ transplantation. This understanding feeds the hypothesis that immunosuppressive drugs targeting the actions of Tfh cells have huge therapeutic potential. This new concept in the treatment of the humoral rejection response will improve graft and patient survival after organ transplantation.


Assuntos
Citotoxicidade Celular Dependente de Anticorpos , Rejeição de Enxerto , Isoanticorpos/imunologia , Transplante de Órgãos , Linfócitos T Reguladores , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/terapia , Humanos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Linfócitos T Reguladores/transplante
13.
Clin Transplant ; 33(12): e13752, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31693247

RESUMO

BACKGROUND: Continuous-flow mechanical circulatory support (CF-MCS) is associated with impaired vascular function and increased risk of vasoplegia. One contributing factor to early graft failure (EGF) is severe vasoplegia. We tested the hypothesis that CF-MCS is associated with increased risk of EGF. METHODS: Adult primary heart transplant recipients in the ISHLT Registry from 2005 to 2013 were stratified into three groups based on pre-transplant MCS: No MCS (n = 11 748), pulsatile (P)-MCS (n = 718), and CF-MCS (n = 3818). EGF was defined as death/retransplantation due to graft failure within 30 days after HT. Comparisons were made using descriptive statistics and associations. EGF was assessed with multivariable Cox proportional hazard regression. RESULTS: The incidence of EGF within 30 days was similar between groups (No MCS 2.2%, P-MCS 3.3%, CF-MCS 2.1%, P = .10). Following multivariable adjustment, the risk of EGF was not statistically different for those with CF-MCS compared with P-MCS (HR 0.75, 95% CI 0.46-1.21, P = .24). The risk of EGF was numerically, but not statistically significantly higher for CF-MCS compared with No MCS (HR 1.24, 95% CI 0.92-1.67, P = .16). CONCLUSION: CF-MCS use was not associated with a statistically significant increased risk of EGF resulting in death or retransplantation in the first 30 days after transplant.


Assuntos
Circulação Extracorpórea/métodos , Rejeição de Enxerto/mortalidade , Insuficiência Cardíaca/mortalidade , Transplante de Coração/mortalidade , Coração Auxiliar/estatística & dados numéricos , Transplante de Pulmão/mortalidade , Complicações Pós-Operatórias/mortalidade , Adulto , Idoso , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/terapia , Sobrevivência de Enxerto , Insuficiência Cardíaca/cirurgia , Transplante de Coração/efeitos adversos , Humanos , Transplante de Pulmão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
14.
BMC Nephrol ; 20(1): 373, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623566

RESUMO

BACKGROUND: Medication non-adherence is a risk factor for acute kidney transplant rejection. The association of non-adherence with short-term allograft loss in patients who develop acute rejection and are subsequently treated with maximal therapy is unknown. METHODS: We conducted a retrospective single center cohort study of adult patients who developed acute rejection from January 2003 to December 2017 and were treated with lymphocyte depletion. Clinicopathologic characteristics including adherence status were collected and descriptive statistics utilized to compare groups. The primary outcome was all-cause graft loss at 6 months after acute rejection treatment. A multivariable logistic regression quantified the association of non-adherence with the outcome. RESULTS: A total of 182 patients were included in the cohort, of whom 71 (39%) were non-adherent. Compared to adherent patients, non-adherent patients were younger (mean age 37y vs 42y), more likely to be female (51% vs 35%) and developed acute rejection later (median 2.3y vs 0.5y from transplant). There were no differences in estimated glomerular filtration rate or need for dialysis on presentation, Banff grade, or presence of antibody mediated rejection between the 2 groups. Overall, 48 (26%) patients lost their grafts at 6 months after acute rejection treatment. In adjusted analysis, non-adherence was associated with all-cause graft loss at 6 months after acute rejection treatment [OR 2.64 (95% CI 1.23-5.65, p = 0.012]. CONCLUSIONS: After adjusting for common confounders, non-adherent patients were at increased risk for short-term allograft loss after a severe acute rejection despite lymphocyte depletion. This finding may aid clinicians in risk stratifying patients for poor short-term outcomes and treatment futility.


Assuntos
Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto , Imunossupressores/uso terapêutico , Adesão à Medicação , Doença Aguda , Adulto , Fatores Etários , Alemtuzumab/uso terapêutico , Aloenxertos , Soro Antilinfocitário/uso terapêutico , Feminino , Rejeição de Enxerto/terapia , Humanos , Transplante de Rim , Depleção Linfocítica , Masculino , Pessoa de Meia-Idade , Muromonab-CD3/uso terapêutico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Adulto Jovem
16.
Emerg Med Clin North Am ; 37(4): 679-705, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31563202

RESUMO

Renal transplants are becoming more and more frequent in the United States and worldwide. Studies demonstrate that these patients inevitably end up visiting an emergency department. In addition to typical medical and surgical problems encountered in the general population, this group of patients has unique problems arising from their immunocompromised state and also due to side effects of the medications required. This article discusses these risks and management decisions that the emergency department physician should be aware of in order to prevent adverse outcomes for the patient and transplanted kidney.


Assuntos
Serviço Hospitalar de Emergência , Transplante de Rim/efeitos adversos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/terapia , Humanos , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/terapia
17.
Stem Cell Res Ther ; 10(1): 290, 2019 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547869

RESUMO

BACKGROUND: Lung transplantation is a life-saving surgical replacement of diseased lungs in patients with end-stage respiratory malfunctions. Despite remarkable short-term recovery, long-term lung survival continues to face several major challenges, including chronic rejection and severe toxic side effects due to global immunosuppression. Stem cell-based immunotherapy has been recognized as a crucial immunoregulatory regimen in various preclinical and clinical studies. Despite initial therapeutic outcomes, conventional stem cells face key limitations. The novel Cymerus™ manufacturing facilitates production of a virtually limitless supply of consistent human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells, which could play a key role in selective immunosuppression and graft repair during rejection. METHODS: Here, we demonstrated the impact of iPSC-derived human MSCs on the development of immune tolerance and long-term graft survival in mouse orthotopic airway allografts. BALB/c → C57BL/6 allografts were reconstituted with iPSC-derived MSCs (2 million/transplant/at d0), and allografts were examined for regulatory T cells (Tregs), oxygenation, microvascular blood flow, airway epithelium, and collagen deposition during rejection. RESULTS: We demonstrated that iPSC-derived MSC treatment leads to significant increases in hTSG-6 protein, followed by an upregulation of mouse Tregs and IL-5, IL-10, and IL-15 cytokines, which augments graft microvascular blood flow and oxygenation, and thereby maintained a healthy airway epithelium and prevented the subepithelial deposition of collagen at d90 post transplantation. CONCLUSIONS: Collectively, these data confirmed that iPSC-derived MSC-mediated immunosuppression has potential to establish immune tolerance and rescue allograft from sustained hypoxic/ischemic phase, and subsequently limits long-term airway epithelial injury and collagen progression, which therapeutically warrant a study of Cymerus iPSC-derived MSCs as a potential management option for immunosuppression in transplant recipients.


Assuntos
Rejeição de Enxerto/terapia , Sobrevivência de Enxerto , Transplante de Células-Tronco Mesenquimais/métodos , Transplante de Órgãos/métodos , Traqueia/transplante , Tolerância ao Transplante , Animais , Células Cultivadas , Rejeição de Enxerto/imunologia , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/imunologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Transplante de Órgãos/efeitos adversos , Linfócitos T Reguladores/imunologia
18.
Transpl Infect Dis ; 21(6): e13164, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31483919

RESUMO

Impaired cell-mediated, as well as antibody-mediated immunity predisposes a renal transplant recipient to a wide variety of atypical infection. With an increasing number of re-transplant, the balance between immunosuppression and the risk of recurrent disease poses a clinical and therapeutic challenge. Here, we report a successful re-transplantation in a case of parvovirus B19 infection leading to anaemia and collapsing glomerulopathy in the allograft managed with intravenous immunoglobulin (IVIG) and reduction of immunosuppression. This case emphasizes re-consideration to renal transplant after clearance of the virus in a previous renal allograft lost to PVB19 infection.


Assuntos
Eritema Infeccioso/tratamento farmacológico , Rejeição de Enxerto/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Transplante de Rim/efeitos adversos , Parvovirus B19 Humano/isolamento & purificação , Aplasia Pura de Série Vermelha/etiologia , Aloenxertos/imunologia , Aloenxertos/virologia , Eritema Infeccioso/complicações , Eritema Infeccioso/imunologia , Eritema Infeccioso/virologia , Glomerulonefrite/imunologia , Glomerulonefrite/cirurgia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/virologia , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Rim/imunologia , Rim/virologia , Doadores Vivos , Masculino , Parvovirus B19 Humano/imunologia , Recidiva , Aplasia Pura de Série Vermelha/tratamento farmacológico , Reoperação , Transplante Haploidêntico/efeitos adversos , Resultado do Tratamento , Adulto Jovem
19.
Transplant Proc ; 51(7): 2254-2256, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31474291

RESUMO

OBJECTIVE: High panel-reactive antibody (PRA) levels limit patients' access to kidney transplantation from potential living donor candidates and decrease renal graft survival by causing acute antibody-mediated rejection (AAMR). In this article, we report our experiences about the efficiency of plasmapheresis (PP) and intravenous immunoglobulin (IVIG) in reduction of serum PRA levels in candidates for renal transplantation and in patients with AAMR. METHODS: We examined retrospectively 47 patients with high PRA levels (18 for desensitization (DS) and 29 with AAMR) at Ankara University. The reduction in PRA class 1 and PRA class 2 levels before and after the PP, IVIG, and rituximab or eculizumab therapy were evaluated. RESULTS: In the DS group, mean reduction in PRA class I ± SD was 28.0 ± 9.10 to 22.1 ± 8.14 (P <.05), and mean reduction in PRA class II ± SD was 40.3 ± 6.89 to 32.2 ± 5.68 (P < .05). In the AAMR group; mean reduction in PRA class I ± SD was 23.9 ± 9.56 to 17.8 ± 8.64 (P > .05), and mean reduction in PRA class II ± SD was 28.1 ± 8.37 to 26.7 ± 7.96 (P > .05). In total, mean reduction in PRA class I was 25.7 ± 6.66 to 19.7 ± 6.00 (P < .01). Mean reduction in PRA class II was 33.8 ± 5.93 to 29.2 ± 4.96 (P > .05). In the DS group, 3 (16.7%) patients were treated with rituximab. In the AAMR group, 9 (31.0%) patients were treated with rituximab, and 1 (5.5%) patient received eculizimab.In the DS group, the mean follow-up period in years ± SD was 5.06 ± 3.01 and no patient had graft loss. In the AAMR group, the mean follow-up period in years was 5.06 ± 2.74 and 6 (33.3%) patients had graft loss with acute rejection. CONCLUSIONS: PP and IVIG treatment provide significant reduction in PRA levels and can be used in DS protocols.


Assuntos
Dessensibilização Imunológica/métodos , Rejeição de Enxerto/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Transplante de Rim/efeitos adversos , Plasmaferese/métodos , Adulto , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Humanos , Fatores Imunológicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Resultado do Tratamento
20.
Nat Rev Drug Discov ; 18(10): 749-769, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31541224

RESUMO

Regulatory T cells (Treg cells) are a small subset of immune cells that are dedicated to curbing excessive immune activation and maintaining immune homeostasis. Accordingly, deficiencies in Treg cell development or function result in uncontrolled immune responses and tissue destruction and can lead to inflammatory disorders such as graft-versus-host disease, transplant rejection and autoimmune diseases. As Treg cells deploy more than a dozen molecular mechanisms to suppress immune responses, they have potential as multifaceted adaptable smart therapeutics for treating inflammatory disorders. Indeed, early-phase clinical trials of Treg cell therapy have shown feasibility, tolerability and potential efficacy in these disease settings. In the meantime, progress in the development of chimeric antigen receptors and in genome editing (including the application of CRISPR-Cas9) over the past two decades has facilitated the genetic optimization of primary T cell therapy for cancer. These technologies are now being used to enhance the specificity and functionality of Treg cells. In this Review, we describe the key advances and prospects in designing and implementing Treg cell-based therapy in autoimmunity and transplantation.


Assuntos
Doenças Autoimunes/terapia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Rejeição de Enxerto/terapia , Neoplasias/terapia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/transplante , Animais , Doenças Autoimunes/imunologia , Rejeição de Enxerto/imunologia , Humanos , Neoplasias/imunologia
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