Navegando por Palavras-chave "Sistema Imune"

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    Associação entre doses elevadas de ácido fólico com ativação de linfócitos T, B e NK e suas possíveis consequências no processo inflamatório em indivíduos saudáveis
    (Universidade Federal de São Paulo (UNIFESP), 2019-12-19) Lucena, Maylla Rodrigues [UNIFESP]; Shinohara, Elvira Maria Guerra [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    BACKGROUND:Folate is a B-complex vitamin withanimportantrole on cell replication since its involvement in DNA and RNA synthesis. In Brazil, most pharmaceutical formulationsof folic acid (FA) taken by women who intend to get pregnant and hemolytic anemia patients contain 5 mg, which is higher than tolerable upper intake levelof this vitamin for healthy subjects. Currently, there is a concern about intake of high doses of FA, once high consumption of FA has been associated to higher folate concentrations on the body, as well as appearanceof an unmetabolized fraction (UMFA). Elevated concentrations of folate and UMFA seem to be implied with changes on immunity. AIM: To assess the association between high doses of FA intake with activation of T, B and NK lymphocytes, and to investigate the possibleimplications in the inflammatory process in healthy individuals.METHODS:34healthy subjects make use of 5mg/day of FA during 90 days. Blood samples were collected at baseline and after 45 and 90 days of FA use. It was assessed: serum and RBC folate, UMFA and other folate forms; vitamin B12; T, B and NK cell activation assays; serum concentrations of interleukin (IL)-6, IL-8, IL-10, interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α).RESULTS:Higher serum and RBC folate, UMFA and 5-methyltetrahydrofolate concentrations were observed after 45 and 90 days of FA use when compared to baseline. Number of T CD4+ cellsincreased, and T CD8+ cells decreased after 90 days of FA use regarding to baseline and 45 days. After 90 days, decreased number of B cells/HLA-DR+ and NK cells/CD38+ after PMA and ionomicin stimulation were observed.CONCLUSIONS:Intake of 5 mg/ day of FA by healthy individuals was associated to increased circulating concentrations of folate, as well as increased number of T CD4+ cells and decreased T CD8+ cells. In addition, our data show relation between FA use and decrease on B and NK cells activation.
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    Papel da Resposta Imune Inata e Adaptativa na Doença Coronária Aterosclerótica em Portadores de Hipercolesterolemia Familiar
    (Universidade Federal de São Paulo (UNIFESP), 2019-08-29) Lopes, Waleria Simone Toledo Fonzar [UNIFESP]; Izar, Maria Cristina De Oliveira [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    BACKGROUND: For hundreds of thousands of years, part of our genomic heritage was primarily developed to combat infectious agents. However, the participation of our immune system modulating the progression of atherosclerosis was only recently recognized in the differential role of lymphocyte subtypes,with B1 lymphocytes with an important antiatherogenic role, due to the production of IgM antibodies that interact with oxidized epitopes of apolipoprotein B, and B2 lymphocytes contributing to atherosclerosis progression favoring interactions of oxidized LDL with dendritic cells, thus contributing for the immune complex deposition in the intima layer and plaque instabilization. Familial Hypercholesterolemia (FH) is an inherited condition characterized by lifetime exposure to high LDL-c, premature atherosclerotic cardiovascular disease (ASCVD) and cutaneous stigmata. However, in spite of LDL-c burden and exposure to aggressive lipid-lowering therapy, there is heterogeneity on atherosclerosis presentation that cannot be explained by classical risk factors. Though, we postulated that the imune-inflammatory system could modulate the burden of atherosclerosis in FH patients. OBJECTIVES:Evaluate if the imune-inflammatory system can modulate the development of coronary atherosclerosis in FH patients under high-intensity lipidlowering therapy. METHODS: One-hundred and two patients with definite or probable diagnosis of FH (Dutch Lipid Clinic Network) were selected. Blood samples for laboratory tests (lipids, biochemistry, apolipoproteins A1, B and Lp(a), immune profile (absolute count and %of lymphocytes TCD4+, TCD8+, B memory cells, B naive, B1, ELISPOT assays, quantification of cytokines TNF-α, IFN-, IL-10, IL-6, IL-4, and IL-2 produced by B memory, B naive and T cells), quantification of monocitic, endothelial and platelet microparticles (flow citometry), and titers of autoantibodies of IgG and IgM isotype anti-oxLDL and anti-Apo B-D (ELISA) were assayed. Genetic study used NGS and a gene pannel with LDLR, APOB, PCSK9, LDLRAP1, APOL1andLIPAgenes. Coronary angiotomography and coronary calcium score (CCS) were performed for the evaluation of the extent and severity of coronary atherosclerosis. Data was compared among individuals with CCS = 0 vs. > 0, among categories of CCS (0; 1-99; 100-399; xxiv 400-999; > 1000 UA), CCS percentiles ( P75) and CAD-RADS categories (0-5). Statistical analysis used parametric and non-parametric tests, as appropriate, with significance set at a P-value < 0,05. RESULTS: CCS> 0 was more prevalent in males (P=0.015), smokers (P=0.016), in those with higher CAD-RADS score (P<0.001), but did not differ among intensities of treatment, presence of cardiovascular risk factors or clinical manifestations of ASCVD. Lipid parameters were similar among participants with CCS = 0 vs. CCS >0 (LDL-c 149 + 61 vs. 158 + 63, respectively; P=0.471). There was heterogeneity in the presentation of ASCVD, with mean and maximal CCS of 173 and 2139 UA, respectively. Immune profile variables, autoantibodies of IgG and IgM isotypes anti- LDLox and anti-Apo B-D, and microparticles did not differ among CCS and CADRADS score categories, although there were trends for diferences for some variables. CONCLUSION: Although there is a clear role of the immune-adaptive system in the development, progression and complications of ASCVD, it does not seem to significantly influence the expression of coronary atherosclerosis evaluated by angiotomography, in subjects with familial hypercholesterolemia under high-intensity lipid-lowering therapy. The expression of ASCVD in those individuals seems to result fromthe balance between long-term exposure to very high levels of LDL-c and highintensity lipid-lowering treatment.