Simone Cristina Olenscki Gilli

Mature autologous dendritic cell vaccines in advanced non-small cell lung cancer: A phase i pilot study

BackgroundOverall therapeutic outcomes of advanced non-small-cell lung cancer (NSCLC) are poor. The dendritic cell (DC) immunotherapy has been developed as a new strategy for the treatment of lung cancer. The purpose of this study was to evaluate the feasibility, safety and immunologic responses in use in mature, antigen-pulsed autologous DC vaccine in NSCLC patients.MethodsFive HLA-A2 patients with inoperable stage III or IV NSCLC were selected to receive two doses of 5 × 107 DC cells administered subcutaneous and intravenously two times at two week intervals. The immunologic response, safety and tolerability to the vaccine were evaluated by the lymphoproliferation assay and clinical and laboratorial evolution, respectively.ResultsThe dose of the vaccine has shown to be safe and well tolerated. The lymphoproliferation assay showed an improvement in the specific immune response after the immunization, with a significant response after the second dose (p = 0.005). This response was not long lasting and a tendency to reduction two weeks after the second dose of the vaccine was observed. Two patients had a survival almost twice greater than the expected average and were the only ones that expressed HER-2 and CEA together.ConclusionDespite the small sample size, the results on the immune response, safety and tolerability, combined with the results of other studies, are encouraging to the conduction of a large clinical trial with multiples doses in patients with early lung cancer who underwent surgical treatment.Trial RegistrationCurrent Controlled Trials: ISRCTN45563569

Transfusion-transmitted infections among multi-transfused patients in Brazil

BACKGROUND Transfusion-transmitted infections (TTI) continue to be a problem in many parts of the world, and multi-transfused patients (MTP) are at a particularly increased risk of TTI. OBJECTIVES to estimate the prevalence of TTI among multi-transfused patients in Brazil, and to understand the epidemiological characteristics of TTI among these patients. STUDY DESIGN cross-sectional study of 353 MTP, who were interviewed using a structured questionnaire and tested for serological markers of hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infection. RESULTS the overall prevalence of HCV, HIV, HBV and co-infection among MTP were 16.7%, 1.7%, 0.8% and 1.7% respectively. A dose-effect relationship could be detected between the number of units transfused and HCV infection. Other non-transfusion related (NTR) risk factors for HCV did not confer any excess risk of HCV infection to MTP. CONCLUSIONS HCV infection was the most prevalent TTI among MTP, and remains a major health problem for these patients. A dose-effect relationship could be detected between HCV and the number of units transfused. The implementation of measures such as donor education programs, standards for donor selection criteria, and of improved serological screening protocols, paralleled the decline in the prevalence of TTI, specially of HCV, observed in MTP, underscoring the importance of such measures for the reduction of the residual risk of TTI.

Molecular matching of red blood cells is superior to serological matching in sickle cell disease patients

Objective To evaluate the usefulness of DNA methods to provide a means to precisely genotypically match donor blood units for the antigen-negative type of 35 sickle cell disease patients. Methods Red blood cell units were investigated for ABO, D, C, c, E, e, K, Fya, Fyb, Jka, Jkb, S, s, Dia and RH variants by performing a molecular array (Human Erythrocyte Antigen BeadChipTM, BioArray Solutions), polymerase chain reaction followed by restriction fragment length polymorphism analysis and sequencing of patient samples and donor units that had been serologically matched based on the ABO, Rh and K phenotypes and the presence of antibodies. Results Matches for 21 of 35 sickle cell disease patients presented discrepancies or mismatches for multiple antigens between the genotype profile and the antigen profile of their serologically-matched blood units. The main discrepancies or mismatches occurred in the RH, FY, JK and MNS systems. Eight Rh alloimmunized patients presented RHD and RHCE variants that had not been serologically identified. According to these results better matches were found for the patients with genotyped units and the patients benefited as shown by better in vivo red blood cell survival. Conclusion Molecular matching is superior to serological matching in sickle cell disease patients, decreasing the risk of transfusion reactions, especially delayed transfusion reactions to existing alloantibodies and preventing alloimmunization.

Red blood cell alloimmunization in patients with sickle cell disease: correlation with HLA and cytokine gene polymorphisms.

The reason for the difference in susceptibility to red blood cell (RBC) alloimmunization among patients with sickle cell disease (SCD) is not clearly understood and is probably the result of multiple factors. Our hypothesis is that genetic polymorphisms are associated with RBC alloimmunization.

The effects of exchange transfusion for prevention of complications during pregnancy of sickle hemoglobin C disease patients.

Pregnancy represents a challenge for women with sickle cell disease (SCD), with higher rates of both maternal and fetal complications. The aim of this study was to evaluate the impact of prophylactic transfusion support administered specifically to pregnant women with sickle hemoglobin C disease.

IL10 inversely correlates with the percentage of CD8 + cells in MDS patients

The role of the immune system in myelodysplastic syndrome (MDS) progression has been widely accepted, although mechanisms underlying this immune dysfunction are not clear. CD4(+) and CD8(+) lymphocyte profiles in the peripheral blood of MDS patients were evaluated and correlated with clinical characteristics, the expression of FOXP3 and the anti-inflammatory cytokines IL10, TGFβ1 and CTLA4. IL10 expression inversely correlated with the percentage of CD8(+) cells and was higher in high-risk MDS. Our findings provide further evidence for the role of T cell-mediated IL10 production in MDS and strengthen the idea of distinct cytokine profiles in low and high-risk MDS.

IL4 and IFNalpha generation of dendritic cells reveals great migratory potential and NFkB and cJun expression in IL4DCs

Dendritic cells (DCs) recently revealed as a potent tumor vaccine component, are commonly differentiated from monocytes by cultivation with IL-4 and GM-CSF. Despite the different opinions, the use of IFNalpha can promote DCs differentiation and activation. The aim of this study was to compare the functionality and phenotypic characterization of monocyte-derived DC generated by IL-4 (IL4DC) and IFNalpha (IFNalphaDC) modified protocols. To this aim, we investigated the expression of maturation markers, co-stimulatory molecules, relevant miRNA, cytokine and migratory profiles and the functional ability of these cells to stimulate autologous T cells in vitro. We herein investigated the molecular mechanism underlying the parameters previously described, as the relative expression of NF-kB p65, c-fos and c-jun, transcription factors. Our results demonstrated that IL4DC presented a stable phenotype, an increase in migratory capacity and NF-KB activation, in addition to lower levels of miR-146 a and miR-221. We believe that the IL4DC migratory potential and increase in NFkBp65 expression may be involved in higher IL12 expression and migration, suggesting a preferential activation of TH1 immune responses by IL4DC.

Platelet associated IgG may be related with thrombocytopenia in patients with myelodysplastic syndromes.

Thrombocytopenia is common in patients with myelodysplastic syndromes (MDS) and immune destruction of platelets could be an important factor for its occurrence. We prospectively analyzed platelet-associated IgG (PAIgG) through platelet immunofluorescence test (PIFT), mean platelet volume (MPV), platelet size deviation width (PDW) and glycocalicin index (GCI) of 54 patients with MDS, classified according to the International Prognostic Scoring System (IPSS). Thrombocytopenia (platelet count<100×10(9)/L) was correlated with a higher amount of PAIgG, significantly higher MPV and increased GCI. In addition, worse prognosis IPSS groups were associated with a higher positivity of PIFT, which could be indicative of advanced disease.

Prevalence of transfusion-transmitted Chagas disease among multitransfused patients in Brazil

BackgroundBlood transfusion has always been an important route for Chagas Disease (CD) transmission. The high prevalence of CD in Latin America and its lifelong asymptomatic clinical picture pose a threat for the safety of the blood supply. The outcome of measures designed to improve transfusion safety can be assessed by evaluating the prevalence of CD among multitransfused patientsMethodsIn order to assess the impact of CD control measures on the safety of the blood supply, an observational cross-sectional study was designed to determine the prevalence of CD in 351 highly transfused patients, in which vectorial transmission was excluded. This study compared patients that received transfusion products before (n = 230) and after (n = 121) 1997, when measures to control transfusion-transmitted CD were fully implemented in Brazil.ResultsThe study group consisted of 351 patients exposed to high numbers of blood products during their lifetime (median number of units transfused = 51, range 10–2086). A higher prevalence of transfusion-transmitted CD (1.30%) was observed among multitransfused patients that received their first transfusion before 1997, compared with no cases of transfusion-transmitted CD among multitransfused patients transfused after that year. The magnitude of the exposure to blood products was similar among both groups (mean number of units transfused per year of exposure = 25.00 ± 26.46 and 23.99 ± 30.58 respectively; P = 0.75, Mann-Whitney test).ConclusionMultiple initiatives aimed to control vector and parental transmission of CD can significantly decrease transfusion-transmitted CD in Brazil. Our data suggest that mandatory donor screening for CD represents the most important measure to interrupt transmission of CD by blood transfusions.

Genotype frequencies at codon 129 of the Prion Protein Gene in Brazil: implications in susceptibility to variant Creutzfeldt--Jakob disease compared to European and Asian populations

A polymorphism at codon 129 of the prion protein gene has been shown to confer genetic susceptibility to prion diseases, and to influence the epidemic course of variant Creutzfeldt--Jakob disease. We employed a PCR-endonuclease digestion-based assay to investigate this genetic trait in Brazil, and then compared our results to previously published data from several European and Asian countries.