Mutação G20210A no gene da protrombina, fator V de Leiden e anticorpos anticardiolipina não influenciam a sobrevida do enxerto renal após o transplante / Prothrombin G20210A gene mutation, factor V Leiden and anticardiolipin antibodies do not influence renal graft survival after transplantation

Introdução: Complicações tromboembólicas são importantes fatores de risco para perda do enxerto e pior evolução após o transplante renal. pacientes com defeito trombofílico apresentam maior risco de complicações tromboembólicas. Foram analisados, entre receptores de transplante renal, a prevalência de defeito trombofílico e o risco atribuído a esta condição para a perda do enxerto e para o desenvolvimento de tromboses intravasculares. Métodos: estudo do tipo coorte incluindo 388 receptores adultos analisados quanto à presença de trombofilia de acordo com a pesquisa de anticorpos anticardiolipidina (aCL) por ELISA e das mutações G1691A no gene do fator V (FV) e G20210A no gene da protrombina (PT) por PCR multiplex. Resultados: Defeito trombofílico foi identificado em 25,8% dos pacientes. As taxas de sobrevida de 2 anos do enxerto foram semelhantes entre os pacientes com e sem defeito trombofílico (94%, p=0,53), bem como a sobrevida dos enxertos livres de tromboses intravasculares (97% versus 97%, p=0,83). pacientes com defeito trombofílico apresentaram prevalência de tromboses intravasculares semelhante à do grupo-controle (3% versus 3,5%, p=0,82). O transplante renal anterior foi associado a maior risco de perda de enxerto (OR 20,8, p<0,001) e de ocorrência de trombose intravasculares (OR 6,8, p=0,008). Conclusões: As prevalências das mutações FVG1691A e PTG20210A na população estudada foram semelhantes às da população geral não transplantada, e a prevalência de anticorpos aCL superou a observada entre os indivíduos sadios. Não houve associação entre os marcadores de trombofilia estudados e a sobrevida em médio prazo do transplante renal.

Introduction: Thromboembolic complications are important risk factors for graft loss and poor outcome after renal transplantation. patients with thrombophilic defects are at increased risk of thromboembolic complications. Were analyzed, among kidney transplant recipients, the prevalence of thrombophilic defects and the risk attributed to this condition for graft loss and the development of intravascular thrombosis. Methods: A cohort study including 388 adult recipients analyzed for the presence of thrombophilia according to anticardiolipidina antibodies (aCL) by ELISA and gene mutations G1691A in factor V (FV) and prothrombin gene G20210A (PT) by multiplex PCR. Results: thrombophilic defect was identified in 25.8% of patients. The survival rates of two years of the graft were similar between patients with and without thrombophilic defect (94%, p = 0.53), and the survival of free grafts of intravascular thrombosis (97% versus 97%, p = 0 , 83). patients with an increased prevalence of thrombophilic defect intravascular thrombosis similar to the control group (3% versus 3.5%, p = 0.82). Previous renal transplantation was associated with increased risk of graft loss (OR 20.8, p <0.001) and intravascular thrombosis (OR 6.8, p = 0.008). Conclusions: The prevalence of mutations and FVG1691A PTG20210A in this study were similar to those of the general population not transplanted, and the prevalence of aCL antibodies exceeded that observed among healthy individuals. There was no association between markers of thrombophilia studied and medium-term survival in renal transplantation.

Genetic polymorphisms of glutathione s-transferase mu1 and theta1 in patients with acquired aplastic anemia: a Brazilian experience

The causes of acquired aplastic anemia (AAA) include immunologic mechanisms and oxidative DNA damage. Glutathione S-transferase (GST) plays an important role in detoxification. In humans, GST genes encode four main clones: alpha (A), mu (M), pi (P) and theta (T). Among GST genes, GST M1 and T1 have null genotypes that result in a lack of activity. The aim of this study was to investigate polymorphisms of the GSTM1 and GSTT1 enzyme in Brazilian patients with AAA. The null allele of GSTM1 was observed in 3 (16.6 percent) patients and the GSTT1 null genotype was observed in only one (5.5 percent) patient. This study did not find any association between genetic polymorphisms of the GSTM1/GSTT1 detoxifying enzymes and the pathogenesis of AAA.

As causas de anemia aplástica adquirida (AAA) incluem mecanismos imunológicos e oxidativos de lesão ao DNA. Glutathiona S-transferase (GST) é fundamental na detoxicação celular. Em humanos, os genes da GST são codificados por quatro clones: alpha (A), mu (M), pi (P) e theta (T). Entre os genes da GST, GST M1 e T1 possuem um genótipo nulo que resulta em ausência de atividade enzimática. O objetivo deste estudo foi investigar os polimorfismos das enzimas GSTM1 e GSTT1 em pacientes brasileiros portadores de AAA. O alelo nulo da GSTM1 foi observado em três (16.6 por cento) pacientes e o GSTT1 nulo foi observado somente em um (5.5 por cento) paciente. Este estudo não encontrou associação entre os polimorfismos genéticos das enzimas de detoxicação GSTM1/ GSTT1 e a patogênese da AAA.

Possible influence of clinical stage and type of treatment in the persistence of residual circulating t(14;18)-positive cells in follicular lymphoma patients.

Many patients with follicular lymphoma (FL) achieve response after treatment but complete remission (CR) rates are very low. Thus the majority of them will relapse, mainly those in advanced stage disease, due to the persistence of residual disease. Therefore, this study had the following aims: to determine the presence of bcl-2/IgH rearrangement in peripheral blood of early and advanced stage FL patients after treatment and to correlate it with their clinical situation at the same moment. We obtained 100 consecutive peripheral blood samples from 30 FL cases and conducted molecular studies using two separate semi-nested PCRs for MBR and mcr rearrangements. These semi-nested PCRs for bcl-2/IgH rearrangement were able to detect one positive cell among 10,000 normal cells. Clinical and molecular evolution of patients diagnosed as early stage disease suggested that molecular response could be obtained even with conventional chemotherapy or radiotherapy. In this group of patients, 64% achieved molecular response in some point during follow-up. However, only 23% of patients diagnosed as advanced stage disease reached molecular response when treated with chemotherapy (with or without radiotherapy). Due to the low number of subjects assessed in this study, we only found a tendency to significance when clinical stage at the diagnosis was associated to molecular response (P = 0.095). We observed 100% of concordance between clinical remission and molecular response in patients after bone marrow transplantation or in those cases treated with monoclonal antibody anti-CD20. This retrospective study, performed in a restricted number of patients, suggests that molecular response can be obtained in FL patients diagnosed at early stage disease, even with conventional chemotherapy and radiotherapy. In advanced stage disease, concordance between clinical remission and molecular response was observed in the majority of patients after bone marrow transplantation or in those cases treated with monoclonal antibody anti-CD20. The prognostic significance of this data should be confirmed with extended follow-up and in a larger number of patients.

Correlation between histological subtype and type of bcl-2/IgH rearrangement in follicular lymphomas.

The aims of this study were: 1) to identify the type of bcl-2 rearrangement in a Brazilian group of FL patients and 2) to correlate it to clinical features, International Prognostic Index (IPI), histological subtype, response to treatment and clinical outcome. We reviewed the diagnosis of 48 patients with FL and investigated the type of bcl-2 gene rearrangement using DNA from paraffin-embedded tumor samples obtained at the time of diagnosis. In 30 cases, we also obtained consecutive peripheral blood samples to search for the presence of bcl-2/IgH rearrangement. Molecular analysis identified 41 (86%) patients with MBR and 5 (10%) patients with mcr rearrangement. In this study, the type of rearrangement was not associated with clinical characteristics or IPI. In addition, the type of rearrangement did not have an impact on response to initial treatment or on clinical outcome. However, we found an association between the type of rearrangement and the histological subtype of FL, i.e., none of mcr-positive patients presented histological grade I (p = 0.043). In this study, we could not demonstrate a relationship between the type of bcl-2 rearrangement and the response to treatment or outcome. However, we found a relationship between the type of rearrangement and FL histological subtype, information not previously reported.