Relação Entre Níveis Séricos De Cd30 E Evolução Do Transplante Renal

The Cd30 Molecule, Of The Tumor Necrosis Factor Receptor Superfamily (Tnfrs8), Is Expressed On Activated Lymphocytes. Cleavage Of Its Extracellular Portion Results In Soluble Cd30 (Scd30) Whose Levels Correlate With Clinical Outcomes In Renal Transplantation. Objective: To Investigate Renal Transplant Patients If Serum Levels Of Scd30 Are Associated With Lesions In Protocol Biopsies 3 And 24 Months Post-Transplantation, With Type Of Immunosuppression, Presence Of Cd30 + Cells In The Graft, Gene Expression Of Cd30 And Related Genes In Cells Peripheral Blood Mononuclear Cells. To Investigate The Influence Of Immunosuppressants On Cell Culture. Patients And Methods: The Study Was Conducted In 169 Low-Risk Immunoglobulin Receptors With Reduced Exposure To Tacrolimus (Ct), Randomized At 3 Months To Be Converted Or Not To Sirolimus (Srl). A Mixed Culture Of Lymphocytes And Cd30 + Hodgkin's Lymphoma Cell Line Was Performed For In Vitro Evaluation Of Cd30 Release And Expression After Treatment With Srl, Everolimo (EvA Molécula Cd30, Da Superfamília Dos Receptores Do Fator De Necrose Tumoral (Tnfrs8), É Expressa Em Linfócitos Ativados. A Clivagem De Sua Porção Extracelular Resulta No Cd30 Solúvel (Scd30) Cujos Níveis Se Correlacionam Com Desfechos Clínicos No Transplante Renal. Objetivo: Investigar Em Pacientes Transplantados Renais Se Níveis Séricos De Scd30 Estão Associados Com Lesões Em Biópsias Protocolares 3 E 24 Meses Pós-Transplante, Com O Tipo De Imunossupressão, Presença De Células Cd30+ No Enxerto, Expressão Gênica De Cd30 E De Genes Relacionados Em Células Mononucleares Do Sangue Periférico. Investigar A Influência Dos Imunossupressores Em Cultura Celular. Casuística E Métodos: O Estudo Foi Conduzido Em 169 Receptores De Rim De Baixo Risco Imunológico, Com Exposição Reduzida Ao Tacrolimo (Tac), Randomizados Aos 3 Meses Para Serem Convertidos Ou Não Para Sirolimo (Srl). Foi Realizada Cultura Mista De Linfócitos E De Linhagem Celular De Linfoma De Hodgkin Cd30+ Para Avaliação In Vitro Da Liberação E Expressão DeDados abertos - Sucupira - Teses e dissertações (2018

HLA-antibodies, anti-MICA and serum levels of CD30 soluble: relatioship to renal graft survival

Objetivo: O propósito do presente estudo foi avaliar a relação de anticorpos anti-HLA e anti-MICA, assim como de níveis séricos de CD30 solúvel (sCD30) com a ocorrência de perda do enxerto por nefropatia crônica do enxerto (PE-NCE) e com tipos de alterações histológicas em biópsias do enxerto com NCE. Métodos: O trabalho foi realizado em uma coorte de 512 receptores com enxerto renal funcionante por pelo menos três anos por ocasião da coleta de uma primeira amostra de sangue, sendo que uma segunda amostra foi coletada 3,96 (3,2 - 5,0) anos após. Nesta coorte, constituída em 2002, foi anteriormente demonstrada associação entre anticorpos anti-HLA classe II, revelados por ELISA, e PE-NCE. No presente trabalho, determinamos, nas mesmas amostras de soro utilizadas no trabalho anterior, níveis séricos de sCD30 por ELISA (BenderMedSystems, Austria), e a presença de anticorpos anti-HLA e anti-MICA, utilizando tecnologia Luminex® (LabScreen Mixed, One Lambda), com o ponto de corte de positividade estabelecido como nMFI ≥10% da nMFI do controle positivo. A creatinina sérica do dia da coleta da amostra foi considerada. Análises estatísticas incluiram teste de log-rank para comparação de curvas de sobrevida de Kaplan-Meier, análise de regressão de Cox, teste de Mann-Whitney, teste exato de Fisher e correlação de Spearman. Resultados: Os riscos relativos (RR) para PE-NCE em período mínimo de 6,1 anos após a coleta de sangue conferidos por anticorpos anti- HLA classe II detectados por ELISA (RR=2,46) e por Luminex® (RR=1,98) não diferiram significativamente. Anticorpos anti-MICA não se associaram com PE-NCE, enquanto que níveis elevados de sCD30 e de creatinina sérica ≥ 2mg/dL, conferiram RRs de 2,14 e 8,61, respectivamente. A ocorrência simultânea de anticorpos anti-HLA classe II (ELISA), níveis elevados de sCD30 e de creatinina conferiu RR de 36,9 para PE-NCE. Anticorpos anti-HLA classe II se associaram a lesões glomerulares, e níveis elevados de sCD30, a lesões intersticiais e vasculares, enquanto creatinina ≥ 2mg/dL se associou aos três tipos de lesão. Conclusão: A avaliação simultânea de anticorpos anti-HLA II, níveis séricos de sCD30 e creatinina é uma ferramenta importante para estimar risco de perda do enxerto por NCE, no período pós-transplante tardio.Associação Fundo de Incentivo à Psicofarmacologia (AFIP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP: 2008/56110-0TEDEBV UNIFESP: Teses e dissertaçõe

ANTI-HLA II ANTIBODIES and CHRONIC REJECTION.

Universidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Association of high post-transplant soluble CD30 serum levels with, chronic allograft nephropathy

The purpose of this study was to evaluate the association of post-transplant soluble CD30 (sCD30) levels, isolated or in combination with of anti-HLA class II antibodies and of serum creatinine levels, with kidney graft loss due to chronic allograft nephropathy (CAN), and type of lesions in graft biopsies for cause. the study comprised 511 first kidney graft recipients, transplanted at a single center, with a graft functioning for at least 2.8 years. A single blood sample was collected from each patient sCD30 levels were determined by ELISA, and HIA antibodies by Luminex assay. the minimum follow-up after testing was 93 years. High sCD30 levels, set at sCD30 >= 3.415 ng/mL, the presence of HLA class II antibodies, and serum creatinine >= 1.9 mg/dL were independently associated with CAN-graft loss (P values <0.0001, 0.05, <0.0001, respectively), and the combined hazard ratio for CAN-graft loss was 20.2. Analyses of 166 biopsies for cause showed that high sCD30 levels and creatinine were independently associated with interstitial lesions. Post-transplant sCD30 serum levels, especially in conjunction with information regarding HLA class II antibodies and serum creatinine levels, provide valuable information regarding graft outcome and could be useful for the management of kidney transplant recipients. (C) 2013 Elsevier B.V. All rights reserved.Associacao Fundo de Incentivo a Pesquisa (AFIP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)AFIP, Inst Immunogenet, BR-04040031 São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilHosp Rim & Hipertensao, São Paulo, BrazilUniv Fed Parana, BR-80060000 Curitiba, PR, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilFAPESP: 2008/56110-0Web of Scienc

INFLUENCE OF IMMUNOSUPPRESSION ON SCD30 LEVELS AND ASSOCIATION OF SCD30 LEVELS WITH CMV INFECTION/DISEASE IN KIDNEY TRANSPLANT RECIPIENTS UNDER DIFFERENT IMMUNOSUPPRESSIVE REGIMENS

Univ Fed Sao Paulo, Immunogenet Inst AFIP, Sao Paulo, BrazilHosp Rim & Hipertensao, Sao Paulo, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilUniv Clin Cologne, Cologne, GermanyUniv Fed Sao Paulo, Immunogenet Inst AFIP, Sao Paulo, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilWeb of Scienc

Influence of immunosuppressive drugs on the CD30 molecule in kidney transplanted patients

Background: Soluble CD30 (sCD30) is a suggested marker for kidney transplantation outcomes. We investigated whether sCD30 serum levels are influenced by immunosuppression and whether they correlate with findings in protocol biopsies and with CD30 gene expression in peripheral blood mononuclear cells (PBMC). Methods: We studied 118 kidney transplant recipients that initially received tacrolimus (TAC) and, at month-3, were converted or not to sirolimus (SRL). Results: sCD30 serum levels gradually declined after transplantation, being the decline more pronounced in the SRL group. CD30 gene expression in PBMC was higher in the SRL group than in the TAC group. Patients with IF/TA >= I in the month-24 protocol biopsy had higher sCD30 levels than patients without IF/TA, in the SRL group (P=.03) and in the TAC group (P=.07). CD30 cells were observed in three out of 10 biopsies with inflammatory infiltrate from the SRL group. In mixed lymphocyte cultures, SRL and TAC diminished the number of CD30(+) T cells and the sCD30 levels in the supernatant, but the effect of SRL was stronger. Conclusions: Overall, sCD30 levels are lower in SRL-treated patients, but the association between increased sCD30 levels and IF/TA at month-24 post-transplantation is stronger in SRL than in TAC-treated patients

Post-transplant soluble CD30 levels are associated with early subclinical rejection in kidney transplantation

Several studies have shown association of high pre- or post-transplant levels of soluble CD30 (sCD30) with acute rejection and poor late kidney transplant outcome. Our goal was to investigate whether sCD30 levels at month-3 post-transplant are associated with subclinical rejection, presence of CD30(+) cells within the graft, and expression of immune response genes in peripheral blood mononuclear cells. the study comprised 118 adult first kidney graft recipients, transplanted at a single center, receiving tacrolimus in low concentration. All were submitted to a protocol biopsy at month-3. Subclinical rejection was identified in 10 biopsies and sCD30 levels >= 61.88 ng/mL (P = 0.004), younger recipient age (P = 0.030) and non-Caucasian ethnicity (P = 0.011) were independently associated with this outcome. Rare CD30(+) cells were present in only two biopsies. There was a correlation between sCD30 levels and CD30 gene expression in peripheral blood mononuclear cells (r = 0.385, P = 0.043). These results show that high sCD30 levels are independent predictors of graft dysfunction and may contribute to patient selection protocols by indicating those who could benefit from a more thorough evaluation. (C) 2015 Elsevier B.V. All rights reserved.Associacao Fundo de Incentivo A Pesquisa (AFIP)AFIP, Inst Imunogenet, BR-04040031 São Paulo, SP, BrazilUniversidade Federal de São Paulo, BR-04021001 São Paulo, SP, BrazilHosp Rim & Hipertensao, BR-04038002 São Paulo, SP, BrazilUniv Fed Parana, BR-80060000 Curitiba, Parana, BrazilUniversidade Federal de São Paulo, BR-04021001 São Paulo, SP, BrazilWeb of Scienc