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2.
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
3.
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
4.
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
5.
Cardiovasc Pathol ; 42: 59-63, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31351216

RESUMO

This article reviews the surgical considerations of cardiac allograft rejection after heart transplantation and describes current treatment modalities for the failing graft. Cardiac allograft rejection can be a moribund diagnosis, especially when it is acute and high grade. It is broadly categorized into hyperacute, acute cellular, and antibody-mediated rejection. Treatment includes a multitude of medical and immunomodulation therapies for graft recovery. Severe rejection requires mechanical circulatory support for hemodynamic stability to maintain end-organ function. Retransplantation for graft loss is the ultimate therapy; however, it portends poor outcomes.


Assuntos
Oxigenação por Membrana Extracorpórea , Rejeição de Enxerto/terapia , Sobrevivência de Enxerto/efeitos dos fármacos , Cardiopatias/terapia , Transplante de Coração/efeitos adversos , Coração Auxiliar , Imunossupressores/uso terapêutico , Oxigenação por Membrana Extracorpórea/efeitos adversos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/fisiopatologia , Cardiopatias/etiologia , Cardiopatias/patologia , Cardiopatias/fisiopatologia , Humanos , Imunossupressores/efeitos adversos , Recuperação de Função Fisiológica , Reoperação , Fatores de Risco , Resultado do Tratamento
6.
Int Rev Immunol ; 38(3): 106-117, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31233364

RESUMO

A growing body of evidence shows that donor-specific antibodies (DSA) are associated with rejection and allograft failure following both liver and intestinal transplantation. However, data have clearly shown that not all DSA are injurious. The reasons for this remain unclear but appear to be multifactorial, impacted by clinical factors such as immunosuppression and infection as well as immunologic factors such as HLA expression and donor-specific antibodies affinity. Establishing a diagnosis of antibody-mediated rejection (AMR) remains clinically challenging, especially given that AMR can present as either acute or chronic graft dysfunction. These observations highlight the need for a better understanding of the immune mechanisms by which DSA and AMR contribute to rejection and allograft failure. This review focuses on current knowledge of DSA and AMR in liver and intestinal transplant recipients and specifically highlights the clinical impact, prevalence, and pathogenesis.


Assuntos
Intestinos/transplante , Isoanticorpos/imunologia , Transplante de Fígado/efeitos adversos , Doadores de Tecidos , Doença Aguda , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Doença Crônica , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/terapia , Antígenos HLA/imunologia , Humanos , Transplante de Fígado/métodos , Prevalência , Fatores de Risco , Transplante Homólogo
7.
Transplant Rev (Orlando) ; 33(3): 173-181, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31060880

RESUMO

Intestinal transplantation (ITX) constitutes a salvage treatment for irreversible intestinal failure and failure of parenteral nutrition. Chronic rejection (CR) remains the key obstacle for long-term intestinal graft survival but the pathomechanisms are incompletely understood. This study systematically reviews experimental models addressing CR after ITX in order to summarize current knowledge on CR pathogenesis and identify promising experimental strategies. A systematic literature search was conducted in line with the PRISMA guidelines, and 68 out of 677 articles qualified for the final analysis. The average methodological quality of the studies was suboptimal with 7 out of 11 points as assessed by a modified Oxford Centre for Evidence-Based Medicine score. Histology of the chronically rejected graft was almost universally integrated as outcome parameter but we found significant heterogeneity in utilized transplant techniques, organ preservation, immunosuppression and time points of CR-assessment. Several studies identified cellular and humoral immunologic mechanisms in chronic intestinal rejection. Yet, neither preventive nor therapeutic strategies against CR have been successfully introduced into human intestinal transplantation highlighting the persistent need for optimized experimental models. In this review, we aim to improve the translational value of forthcoming investigations on CR by discussing the experimental status quo and potential innovative approaches.


Assuntos
Rejeição de Enxerto/etiologia , Rejeição de Enxerto/terapia , Intestinos/transplante , Transplante de Órgãos/efeitos adversos , Animais , Modelos Animais de Doenças , Rejeição de Enxerto/diagnóstico
8.
Med Clin North Am ; 103(3): 425-433, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30955511

RESUMO

Lung transplantation is an appropriate therapeutic option for select patients with end-stage lung diseases and offers the possibility of improved quality of life and longer survival. Unfortunately, the transplant recipient is at risk for numerous immunologic, infectious, and medical complications that threaten both of these goals. Median survival after lung transplantation is approximately 6 years. Optimizing outcomes requires close partnership between the patient, transplant center, and primary medical team. Early referral to a transplant center should be considered for patients with idiopathic pulmonary fibrosis and related interstitial lung diseases due to risk of acute exacerbation and accelerated development of respiratory failure.


Assuntos
Pneumopatias/cirurgia , Transplante de Pulmão , Insuficiência Respiratória/cirurgia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/terapia , Humanos , Imunossupressão , Pneumopatias/complicações , Pneumopatias/mortalidade , Transplante de Pulmão/efeitos adversos , Seleção de Pacientes , Encaminhamento e Consulta , Alocação de Recursos , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/mortalidade , Listas de Espera/mortalidade
9.
Int Rev Immunol ; 38(3): 118-128, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31012340

RESUMO

ABO-incompatible liver transplantation (ABOi LT) using conventional immunosuppression has been considered a contraindication due to the high risk for antibody-mediated complications potentially resulting in graft loss. However, organ shortage has led to the development of anti-A/B antibody reducing immunosuppressive protocols which have made the outcome after living donor (LD) ABOi LT equivalent to that achieved with LD ABO-compatible (ABOc). The experience of deceased donor (DD) ABOi LT is however still limited. In this article, we discuss the historical background and the results after ABOi LT, in the setting of both LD and DD transplantation. We also discuss the remaining hurdles and future strategies in the breaching of the ABO barrier for LT.


Assuntos
Incompatibilidade de Grupos Sanguíneos , Transplante de Fígado , Sistema do Grupo Sanguíneo ABO/imunologia , Animais , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/terapia , Sobrevivência de Enxerto/imunologia , Humanos , Fatores Imunológicos/administração & dosagem , Isoanticorpos/imunologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Doadores Vivos , Rituximab/administração & dosagem
10.
Transpl Int ; 32(8): 775-788, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30955215

RESUMO

Late antibody-mediated rejection (ABMR) is a cardinal cause of kidney allograft failure, manifesting as a continuous and, in contrast with early rejection, often clinically silent alloimmune process. While significant progress has been made towards an improved understanding of its molecular mechanisms and the definition of diagnostic criteria, there is still no approved effective treatment. In recent small randomized controlled trials, therapeutic strategies with promising results in observational studies, such as proteasome inhibitor bortezomib, anti-C5 antibody eculizumab, or high dose intravenous immunoglobulin plus rituximab, had no significant impact in late and/or chronic ABMR. Such disappointing results reinforce a need of new innovative treatment strategies. Potential candidates may be the interference with interleukin-6 to modulate B cell alloimmunity, or innovative compounds that specifically target antibody-producing plasma cells, such as antibodies against CD38. Given the phenotypic heterogeneity of ABMR, the design of adequate systematic trials to assess the safety and efficiency of such therapies, however, is challenging. Several trials are currently being conducted, and new developments will hopefully provide us with effective ways to counteract the deleterious impact of antibody-mediated graft injury. Meanwhile, the weight of evidence would suggest that, when approaching using existing treatments for established antibody-mediated rejection, "less may be more".


Assuntos
Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/terapia , Transplante de Rim , Aloenxertos/imunologia , Animais , Anticorpos Monoclonais Humanizados , Bortezomib/uso terapêutico , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Histocompatibilidade , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Isoanticorpos/sangue , Inibidores de Proteassoma , Ensaios Clínicos Controlados Aleatórios como Assunto , Rituximab/uso terapêutico , Transplante Homólogo
12.
J Card Surg ; 34(4): 205-207, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30816595

RESUMO

Mediastinitis is one of the life-threating complications that can occur after cardiac surgery. However, to the best of our knowledge, there has been no report of mediastinitis caused by Mycobacterium chelonae, which is one of the rapidly growing nontuberculous mycobacteria species. As far as we know, our case is the first case describing the curative management for mediastinitis caused by M. chelonae after heart transplantation.


Assuntos
Rejeição de Enxerto/terapia , Transplante de Coração , Mediastinite/microbiologia , Mediastinite/terapia , Infecções por Micobactéria não Tuberculosa , Mycobacterium chelonae , Complicações Pós-Operatórias/terapia , Doença Aguda , Adulto , Antibacterianos/administração & dosagem , Seguimentos , Humanos , Masculino , Tratamento de Ferimentos com Pressão Negativa , Troca Plasmática , Retalhos Cirúrgicos , Irrigação Terapêutica , Resultado do Tratamento
13.
J Cardiovasc Med (Hagerstown) ; 20(4): 264-266, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30720635

RESUMO

: Heart transplantation is a life-saving therapy for some patients admitted for acute myocarditis. However, controversial exists about the major risk of rejection following heart transplantation in specific types of myocarditis. Because of relatively few data on the post heart transplant outcomes, we report the long-term follow-up of a 39-year-old patient with a previous history of ulcerative colitis, which rapidly worsened heart failure until an emergency heart transplant in 2004.The clinical course was complicated by many episodes of rejection; lastly, after the development of severe cardiac allograft vasculopathy, re-heart transplantation was needed. The main findings of this case are: 1) inflammatory aetiology should always be suspected in patients with concomitant autoimmune disease that developing rapidly progressing heart failure; 2) patients with inflammatory myocardial disease undergoing heart transplantation should also undergo strict immunological surveillance; 3) the option of performing the re-heart transplant in a patient with a so complex management in the first one could be uncertain, but in this case the young age and lack of noncardiac comorbidities were effective to favour the survivor after two immunologically so challenging heart transplantation.


Assuntos
Autoimunidade , Colite Ulcerativa/imunologia , Rejeição de Enxerto/imunologia , Transplante de Coração/efeitos adversos , Miocardite/cirurgia , Sarcoidose/cirurgia , Adulto , Biópsia , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/terapia , Angiografia Coronária , Diagnóstico Diferencial , Ecocardiografia , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/terapia , Humanos , Imunossupressores/administração & dosagem , Masculino , Miocardite/diagnóstico , Miocardite/imunologia , Plasmaferese , Valor Preditivo dos Testes , Reoperação , Sarcoidose/diagnóstico , Sarcoidose/imunologia , Choque Cardiogênico/imunologia , Fatores de Tempo , Resultado do Tratamento
14.
J Ren Care ; 45(1): 51-58, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30784227

RESUMO

BACKGROUND: Recipients with failing kidney transplants (RFKTs) may receive sub-optimal care compared with patients with native kidney disease. The aim of this study is to compare the outcomes of RFKTs managed in a dedicated low clearance transplant clinic (LCTC) compared with those attending a general transplant clinic. METHODS: We undertook a retrospective analysis of patients with failing kidney transplants comparing two clinics-a LCTC versus a general transplant clinic. Kidney transplant recipients with an eGFR < 20 ml/min were included. A cross-sectional analysis was undertaken of all patients with two consecutive follow-up visits between the dates of January and July 2016 in either clinic, with follow-up to event or December 2017. RESULTS: Data were analysed for 141 kidney transplant recipients; 60 in the LCTC and 81 in the general transplant clinic. More patients in the LCTC cohort were non-white and early transplant recipients. A significantly greater proportion of LCTC versus general transplant patients had received documented discussions regarding their hepatitis vaccine status (63.3% vs. 17.3%, p < 0.001), counselled regarding dialysis modality (98.3% vs. 55.6%, p < 0.001) and had documented decision regarding re-transplantation (80.0% vs. 58.0%, p = 0.006). No difference was noted in the comparison of any clinical or biochemical parameters. More patients seen in the LCTC lost their kidney allograft (HR: 2.09, 95%CI: 1.17-3.72, p = 0.013) but patient survival was equivalent (p = 0.343). CONCLUSION: Our data suggest the management of RFKTs within LCTCs can focus attention on renal replacement therapy planning and counselling, but further work is warranted to investigate for any benefit in hard outcomes such as survival.


Assuntos
Instituições de Assistência Ambulatorial/normas , Taxa de Filtração Glomerular/fisiologia , Rejeição de Enxerto/terapia , Transplante de Rim/normas , Adulto , Instituições de Assistência Ambulatorial/organização & administração , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Imunossupressão/normas , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Estatísticas não Paramétricas
15.
Exp Clin Transplant ; 17(Suppl 1): 113-119, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30777534

RESUMO

OBJECTIVES: Data on the management of chronic antibody-mediated rejection after kidney transplantation are limited. We aimed to assess the impact of treatment of biopsy-proven chronic active antibodymediated rejection with combined plasma exchange, intravenous immunoglobulin, and rituximab treatment versus intravenous immunoglobulin alone or conservative management on the evolution of renal function in renal transplant recipients. MATERIALS AND METHODS: In this retrospective study, we compared patients diagnosed with chronic active antibody-mediated rejection who were treated with standard of care steroids, intravenous immunoglobulin, plasma exchange, and rituximab (n = 40) at our center versus those who received intravenous immunoglobulin only or just intensified maintenance immunosuppression (n = 28). All patients were followed for 12 months clinically and by laboratory tests for graft and patient outcomes. RESULTS: The two groups were matched regarding mean recipient age (41.9 ± 15.4 vs 37.8 ± 15.5 y in patients with conservative versus combined treatment), recipient sex, mean body weight, and the cause of end-stage kidney disease. Most patients and their donors were males. Glomerulonephritis represented the most common cause of end-stage kidney disease in both groups followed by diabetic nephropathy. The type of induction and pretransplant comorbidities were not different between groups (P > .05) except for the significantly higher number of chronic hepatitis C infections in patients who received conservative treatment (P = .007). Mean serum creatinine values before and after treatment of chronic active antibodymediated rejection were comparable between groups (P > .05). Active treatment with heavier immunosuppression (rituximab and plasma exchange) was associated with posttreatment viral (cytomegalovirus and BK virus) and bacterial infections that necessitated more hospitalization (P > .05). However, graft and patient outcomes were significantly better in the active treatment group than in patients with conservative treatment (P = .002 and .028, respectively). CONCLUSIONS: Combined treatment of chronic active antibody-mediated rejection with plasma exchange, intravenous immunoglobulin, and rituximab can significantly improve outcomes after renal transplant.


Assuntos
Rejeição de Enxerto/terapia , Sobrevivência de Enxerto/efeitos dos fármacos , Imunoglobulinas Intravenosas/administração & dosagem , Imunossupressores/administração & dosagem , Isoanticorpos/imunologia , Transplante de Rim/efeitos adversos , Troca Plasmática , Rituximab/administração & dosagem , Esteroides/administração & dosagem , Adulto , Biópsia , Doença Crônica , Terapia Combinada , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Imunossupressores/efeitos adversos , Isoanticorpos/sangue , Masculino , Pessoa de Meia-Idade , Troca Plasmática/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Rituximab/efeitos adversos , Esteroides/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
Exp Clin Transplant ; 17(Suppl 1): 159-163, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30777545

RESUMO

To avoid graft rejection during pregnancy, frequent monitoring of serum drug levels is recommended. Pregnancy induces hyperfiltration in transplanted kidneys, as in native kidneys; therefore, detection of rejection can be difficult when monitoring by serum creatinine. If rejection is suspected, ultrasonographguided graft biopsy can be done; once proven, it can be treated with pulse steroids, but data are scarce regarding other agents. Here, we present a 28-year-old pregnant female patient with resistant acute rejection but with successful pregnancy outcome. Our patient had end-stage kidney disease secondary to lupus nephropathy and underwent living-donor renal transplant in May 2013 after hemodialysis support for 1 year. She received thymoglobulin as induction therapy and was maintained on prednisolone, mycophenolate mofetil, and tacrolimus. She had normal renal graft function without proteinuria. After she received counseling, she became pregnant in February 2015. In June 2015, she presented with acute graft dysfunction with serum creatinine level of 365 µmol/L. Her abdominal ultrasonography showed mild hydronephrosis and viable fetus. She received empirical pulse steroids with partial response, and her graft biopsy showed acute T-cell-mediated rejection and negative C4d. Intravenous immunoglobulins and minipulse steroids were administered but without response. After gynecologic counseling and informed consent, she received 5 doses of thymoglobulin. She was dialysis dependent until premature vaginal labor, which resulted in birth of a viable 2-kg boy. We suggest that successful pregnancy outcomes could occur with close monitoring and daily dialysis in female kidney transplant patients with resistant rejection.


Assuntos
Soro Antilinfocitário/uso terapêutico , Resistência a Medicamentos , Rejeição de Enxerto/imunologia , Imunidade Celular , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Gravidez não Planejada , Linfócitos T/imunologia , Doença Aguda , Adulto , Soro Antilinfocitário/efeitos adversos , Substituição de Medicamentos , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/terapia , Humanos , Imunidade Celular/efeitos dos fármacos , Imunossupressores/efeitos adversos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Transplante de Rim/métodos , Nascimento Vivo , Doadores Vivos , Nefrite Lúpica/complicações , Ácido Micofenólico/uso terapêutico , Prednisolona/uso terapêutico , Gravidez , Diálise Renal , Fatores de Risco , Linfócitos T/efeitos dos fármacos , Tacrolimo/uso terapêutico , Resultado do Tratamento
17.
BMC Nephrol ; 20(1): 53, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764798

RESUMO

BACKGROUND: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMIGD) is a disease entity classified under the group of "Monoclonal gammopathy-related kidney diseases", and can recur after transplant. Clinical remission of proteinuria in patients with PGNMIGD has been previously shown following anti-B cell and/or anti-plasma cell therapies. Our case is the first to show complete histologic resolution of the glomerular monoclonal IgG kappa deposits in a case of recurrent PGNMIGD in renal allograft after rituximab and steroid treatment. This is a novel finding and it shows that the deposits are amenable to therapy. This case also highlights the importance of IgG subclass staining in the recognition of the monoclonal nature of the deposits. It is particularly important in PGNMIGD because only 20 to 30% of patients with this disease are reported to have detectable monoclonal gammopathy, and the deposits do not have any organized substructure on electron microscopic examination. Morphologically, they resemble polyclonal immune-type deposits seen in other immune complex glomerulonephritides such as lupus nephritis, infection-associated glomerulonephritis, and membranoproliferative glomerulonephritis (MPGN type I). CASE PRESENTATION: The patient is a 44 year old Caucasian male who received a living unrelated donor kidney transplant for end-stage renal disease diagnosed 7 years before transplant. The reported native kidney biopsy diagnosis was membranoproliferative glomerulonephritis (MPGN) with IgG, C3 and kappa restricted deposits. Fourteen months post-transplant, he presented with abrupt worsening of graft function, proteinuria and serum IgG kappa monoclonal spike. Allograft biopsy was consistent with recurrent PGNMIGD, considering the native kidney diagnosis and interval post-transplant. He underwent plasmapheresis, IV pooled immune globulin, steroid pulse and taper, and anti-CD-20 Rituximab therapy. Patient had gradual decline in proteinuria and complete resolution of the immune deposits on repeat biopsy 3 months later. Unfortunately he subsequently developed chronic antibody-mediated rejection and transplant glomerulopathy and graft failure 34 months post-transplant. CONCLUSIONS: In a transplant setting, repeat allograft biopsies are frequently performed for graft dysfunction. This provides a good opportunity to study the evolution of the immune deposits following treatment. Our case shows complete histologic resolution of the deposits in allograft PGNMIGD.


Assuntos
Anticorpos Monoclonais/análise , Glomerulonefrite Membranoproliferativa/patologia , Imunoglobulina G/análise , Imunossupressores/uso terapêutico , Glomérulos Renais/patologia , Paraproteinemias/patologia , Rituximab/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Biópsia por Agulha , Terapia Combinada , Glomerulonefrite Membranoproliferativa/tratamento farmacológico , Glomerulonefrite Membranoproliferativa/imunologia , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Glomérulos Renais/química , Transplante de Rim , Doadores Vivos , Masculino , Paraproteinemias/tratamento farmacológico , Paraproteinemias/imunologia , Plasmaferese , Recidiva , Doadores não Relacionados
19.
Scand J Immunol ; 89(4): e12750, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30664805

RESUMO

Interleukin-35 (IL-35) is a cytokine recently discovered to play a potent immunosuppressive role by intensifying the functions of regulatory T cells and inhibiting the proliferation and functions of T helper 1 and T helper 17 cells. Mesenchymal stem cells (MSCs) have recently emerged as promising candidates for cell-based immune therapy, and our previous study showed that IL-35 gene modification can effectively enhance the therapeutic effect of MSCs in vitro. In this study, we isolated adipose tissue-derived MSCs in vitro and infected them with lentiviral vectors overexpressing the IL-35 gene, thereby creating IL-35-MSCs. Subsequently, IL-35-MSCs were then injected into mice of the allogeneic heterotopic abdominal heart transplant model to determine their effect on allograft rejection. The results showed that IL-35-MSCs could continuously secrete IL-35 in vivo and in vitro, successfully alleviate allograft rejection and prolong graft survival. In addition, compared to MSCs, IL-35-MSCs showed a stronger immunosuppressive ability and further reduced the percentage of Th17 cells, increased the proportion of CD4+ Foxp3+ T cells, and regulated Th1/Th2 balance in heart transplant mice. These findings suggest that IL-35-MSCs have more advantages than MSCs in inhibiting graft rejection and may thus provide a new approach for inducing immune tolerance during transplantation.


Assuntos
Rejeição de Enxerto/terapia , Sobrevivência de Enxerto , Transplante de Coração , Imunoterapia/métodos , Interleucinas/imunologia , Células-Tronco Mesenquimais/imunologia , Linfócitos T Reguladores/imunologia , Tecido Adiposo/citologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Rejeição de Enxerto/imunologia , Humanos , Tolerância Imunológica , Interleucina-17/metabolismo , Ativação Linfocitária , Masculino , Transplante de Células-Tronco Mesenquimais , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Equilíbrio Th1-Th2 , Transplante Homólogo
20.
Surg Today ; 49(5): 443-450, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30617600

RESUMO

PURPOSE: Suppressor of cytokine signaling-3 (SOCS3) is a negative feedback inhibitor of cytokine signaling with T-cell-mediated immunosuppressive effects on obliterative bronchiolitis (OB). In this study, we aimed to investigate the impact of T-cell-specific overexpression of SOCS3 using a murine heterotopic tracheal transplantation (HTT) model. METHODS: Tracheal allografts from BALB/c mice were subcutaneously transplanted into wild-type C57BL/6J (B6; WT) mice and SOCS3 transgenic B6 (SOCS3TG) mice. Tracheal allografts were analyzed by immunohistochemistry and quantitative polymerase chain reaction assays at days 7 and 21. RESULTS: At day 21, allografts in SOCS3TG mice showed significant amelioration of airway obstruction and epithelial loss compared with allografts in WT mice. The intragraft expression of IFN-γ and CXCL10 was suppressed, while that of IL-4 was enhanced in SOCS3TG mice at day 7. The T-bet levels were lower in SOCS3TG allografts than in WT allografts at day 7. CONCLUSION: We revealed that the overexpression of SOCS3 in T cells effectively ameliorates OB development in a murine HTT model by inhibiting the Th1 phenotype in the early phase. Our results suggest that the regulation of the T-cell response, through the modulation of SOCS expression, has potential as a new therapeutic strategy for chronic lung allograft dysfunction.


Assuntos
Obstrução das Vias Respiratórias/genética , Obstrução das Vias Respiratórias/imunologia , Obstrução das Vias Respiratórias/terapia , Expressão Gênica , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Linfócitos T , Traqueia/transplante , Transplante Heterotópico , Aloenxertos , Animais , Bronquiolite Obliterante/genética , Bronquiolite Obliterante/imunologia , Bronquiolite Obliterante/terapia , Doença Crônica , Rejeição de Enxerto/terapia , Tolerância Imunológica , Transplante de Pulmão , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Animais
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