Navegando por Palavras-chave "A Molécula Cd30"

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    Relação entre níveis séricos de CD30 e evolução do transplante renal
    (Universidade Federal de São Paulo (UNIFESP), 2018-06-28) Grenzi, Patricia Cristina [UNIFESP]; Lima, Maria Gerbase de [UNIFESP]; http://lattes.cnpq.br/4057011670367139; http://lattes.cnpq.br/2063655198326734; Universidade Federal de São Paulo (UNIFESP)
    Introduction: The CD30 molecule of the tumor necrosis factor receptor (TNFRS8) superfamily is expressed in activated lymphocytes. The cleavage of the extracellular portion results in the soluble CD30 (sCD30), which correlates with clinical outcomes in kidney transplantation. Objectives: Investigate in kidney transplant recipients whether sCD30 serum levels are associated with lesions in protocol biopsies 3 and 24 months posttransplantation, with immunosuppression type, the presence of CD30+ cells within the graft and gene expression of CD30 and related genes in peripheral blood mononuclear cells. To investigate the influence of immunosuppressive drugs on cell culture. Casuistic and methods: The study was conducted in 169 lowimmunological risk recipients with reduced exposure to tacrolimus (TAC), randomized at 3 months to be converted or not to sirolimus (SRL). Mixed lymphocyte culture and CD30+ Hodgkin's lymphoma cell line culture were performed for in vitro evaluation of CD30 release and expression after treatment with SRL, everolimus (EVR) and TAC. The presence of CD30 on the surface of extracellular vesicles (EVs) was also evaluated. Results: In the third month posttransplantation, subclinical rejection was observed in 10 (8.5%) protocol biopsies and sCD30 levels, recipient age and ethnicity were independently associated with this outcome. We observed a correlation between sCD30 levels and CD30 gene expression (r=0.385, P=0.043). At this time, part of the patients with criteria to continue in the study, were converted to SRL or maintained with TAC, according to the randomization performed in the patient inclusion in the project. In all patients, sCD30 levels decreased gradually, but this decrease was more pronounced in the group converted to SRL (P<0.001), although the CD30 gene expression was higher in these patients.Patients with interstitial fibrosis (IF) / tubular atrophy (TA) ≥ I in the month24 protocol biopsy had higher sCD30 levels than patients without IF/TA, in the SRL group (P=0.03) and in the TAC group (P=0.07). CD30+ cells were observed in three out of 10 biopsies with inflammatory infiltrate from the SRL group. In mixed lymphocyte cultures and in CD30+ Hodgkin lymphoma cell lines, SRL and TAC diminished the number of CD30+ T cells and the sCD30 levels in the supernatant, but the effect of SRL was stronger. In both experiments, inhibition of the mTOR pathway induced greater release of EVs. In the Hodgkin lymphoma cell line cultures, we observed a discrete increase of CD30+ vesicles after treatment with SRL and EVR. Conclusions: Overall, sCD30 levels are lower in SRLtreated patients, but the association between increased sCD30 levels and IF/TA at month24 posttransplantation is stronger in SRL than in TACtreated patients. Apparently, there might be a change in the CD30 release pattern after mTOR inhibition, since expression of the receptor expression on the cell membrane is significantly reduced, as well as the soluble form cleveage, but the receptor can be released on the surface of EVs. The influence of SRL treatment on sCD30 cleavage, which may involve multiple mechanisms.