Navegando por Palavras-chave "Doença Falciforme"

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    Análise da contribuição do inflamassoma na heterogeneidade clínica de pacientes com doença falciforme
    (Universidade Federal de São Paulo (UNIFESP), 2019-11-21) Dutra, Valeria De Freitas [UNIFESP]; Figueiredo, Maria Stella [UNIFESP]; Pontillo, Alessandra [UNIFESP]; http://lattes.cnpq.br/0736747630522639; http://lattes.cnpq.br/1049389129901440; Universidade Federal de São Paulo (UNIFESP)
    In spite of having a molecular basis, Sickle cell disease (SCD) is an inflammatory state with abnormal cell activation. Physiopathological factors are not completely understood, but it is known that interleukins plays an important role in inflammation. Inflammasome complex is an innate immune pathway involved in the production of active IL-1β and IL-18. The participation of this complex in sickle cell disease is still not clear. Polymorphisms of inflammasome are simple amino acid substitution that can lead to a loss or gain of function and may be associated with clinical manifestations. NLRP3 is the most studied and well-known inflammasome, associated especially to auto-inflammatory diseases. Aim: To analyze the contribution of inflammasome to the clinical heterogeneity of SCD. To this, the association of inflammasome gene polymorphisms and a functional in vitro study were performed. Methods: In the association study 161 patients were included. Retrospective data were collected to fill clinical and laboratorial information. Patients were classified in two different groups: mild (0-1) or severe (> 2 organ damage). DNA samples were collected from 88 patients and 73 were used from a biorepository (BR- 116). Minor allelic frequency and literature information were used to choose 10 SNPs. Real-time PCR technique with allele and specific probes was used in TaqMan® assays (Applied Biosystms, Thermo Fisher Scientific). To functional study (n=7), PBMC and monocytes from healthy patients and controls were challenged with LPS and / or ATP, with subsequent IL-1β dosage by the ELISA method. All volunteers received a free and informed consent form. Multivariate analysis were performed by the software R Studio 3.5.3 (www.r-project.org), SNP association package. Mann-Whitney test was applied to group comparison. Results: The gain-offunction polymorphism rs16944 has resulted in a significant protection factor for SCD severity. The loss of function variant in the IL18 gene (rs1834481) was associated to high count of monocytes and leucocytes. In the functional test, patients with SCD tend to have less inflammasome activation when compared to controls. Conclusion: The promoter variant -511 C>T in IL1β resulted significantly associated to mild presentation in SCD patients (padj=0.001). PBM analysis showed that SCD cells seems to be less prone to activate inflammasome than HD.
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    Avaliação do perfil inflamatório na doença falciforme: neutrófilos de baixa densidade (LDNs) e CD177
    (Universidade Federal de São Paulo, 2023-08-17) Leal, Bruno Cardoso [UNIFESP]; Bordin, José Orlando [UNIFESP]; Sacconato, Elyse Moritz [UNIFESP]; http://lattes.cnpq.br/1547047244683289; http://lattes.cnpq.br/4235368036147314; http://lattes.cnpq.br/4619269184481757
    Introdução: Os neutrófilos são células do sistema imunológico essenciais na resposta a infecções e inflamação. Descobriu-se que eles podem ser divididos em subpopulações com funções distintas, como os neutrófilos de baixa densidade (LDNs), relacionados a câncer e doenças inflamatórias como lúpus e artrite reumatóide. É crucial compreender e identificar melhor essas subpopulações de neutrófilos, pois não existem marcadores específicos e sua separação se baseia apenas na densidade. Objetivos: Estudar os neutrófilos de baixa densidade e neutrófilos de densidade normal em pacientes com anemia falciforme quanto à representatividade de cada população e avaliação destas células quanto ao grau de maturação de cada população bem como a expressão da glicoproteína CD177; comparar o perfil de inflamação no grupo de pacientes com anemia falciforme de acordo com a variável de tratamento. Casuística e métodos: Foram analisadas amostras de 63 indivíduos, divididos em grupo controle (21 participantes) e grupo doença falciforme (42 participantes). As amostras foram separadas usando a metodologia de Ficoll por gradiente de densidade e posteriormente analisadas por citometria de fluxo para a caracterização das populações de LDNs e HDNs quanto a estágio maturativo destas células (utilizando os marcadores CD13, C11b e CD16); e expressão da glicoproteína de membrana CD177, utilizando o marcador desta proteína (CD177). Também foram realizados hemograma para a obtenção dos resultados de hemoglobina, hematócrito, plaquetas, reticulócitos, contagem global de leucócitos e neutrófilos; e dosagens bioquímicas dos parâmetros, bilirrubina indireta, proteína c reativa e desidrogenase lática. Resultados: Os resultados foram divididos em quatro análises: grupo inteiro de pacientes com anemia falciforme x grupo controle de indivíduos saudáveis; pacientes tratados com hidroxiureia x grupo controle; pacientes tratados com transfusão x grupo controle; pacientes em tratamento expectante x grupo controle. Na avaliação do parâmetro LDNs, observamos resultados aumentados estatisticamente relevantes nos grupo de pacientes tratado com hidroxiureia (p<0,05) e no grupo tratado com transfusão crônica (p<0,01) quando comparados ao grupo controle. Também foi possível observar um aumento não significativo no grupo geral de pacientes com anemia falciforme (p= 0,12) e no grupo de pacientes em tratamento expectante (p= 0,85) quando comparados ao grupo controle. No parâmetro CD177, ainda que os valores de tendência central estejam aumentados nos diferentes tratamentos: hidroxiureia (47,81%); transfusão (39,4%) e expectante (42,41%), em comparação ao grupo controle (27,3), a análise não apresentou relevância estatística nos dados obtidos. Além disso, observou-se heterogeneidade na maturação dos neutrófilos de baixa densidade, com a presença de neutrófilos maduros e imaturos nesta camada em todos os grupos estudados, porém, embora o valor médio apresentado de neutrófilos, apesar disto, a análise realizada não mostrou diferença estatisticamente relevante nos parâmetros neutrófilos maduros e neutrófilos imaturos nos grupos de pacientes com anemia falciforme quando comparados ao grupo controle. Conclusão: Portanto, este estudo destaca a relevância dos LDNs na inflamação da anemia falciforme, uma informação inédita na literatura científica. Esses resultados abrem caminho para futuras pesquisas sobre a função dos LDNs na anemia falciforme e sua potencialidade como alvo terapêutico.
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    Evaluation of 6-minute walk test (6MWT) in adults with sickle cell disease in São Paulo/SP
    (Universidade Federal de São Paulo (UNIFESP), 2017-03-01) Norvil, Wesny [UNIFESP]; Figueiredo, Maria Stella [UNIFESP]; http://lattes.cnpq.br/0736747630522639; http://lattes.cnpq.br/6652873085167567; Universidade Federal de São Paulo (UNIFESP)
    Introduction: Sickle-cell Disease (SCD) is the hematological disease, with the most hereditary, monogenic and autosomal features in the world. Its pathophysiology involves hemolysis and vaso-occlusion, which can affect several organs, including the lung. It is observed that hypoxemia in the steady state is a common manifestation in SCD and it has been proven an association with the level of anemia and the degree of hemolysis in previous studies. The 6-minutes-walking test (6MWT) is a simple functional capacity test that evaluates the exercise tolerance according to the distance covered in 6 minutes and with monitoring of the behavior of oxygen saturation and blood pressure. It has been gaining importance in sickle cell disease, since lots of results were found showing the impact of baseline oxygen(O2) desaturation in the 6MWT performance in children with sickle cell disease whereas just a few have been found in adults. Objective: In this current study we aimed at evaluating hypoxemia in sickle-cell adults though the 6MWT and its relation with the clinical-laboratory parameters. Methods: A cross-sectional, analytical and descriptive study was performed in 44 patients with SCD and 19 healthy controls based on the 6MWT and clinical-laboratory data. Results: The group of patients covered a shorter distance [median (interquartile): 416.9m (406.6-444.8)] than controls [652.5m (634.4-665.0); p<0001]. No individual in the control group had baseline or post-test desaturation. Moderate O2 desaturation at rest (defined as SpO2<95%) was observed in 25.0% (n=11) of the patients. The distance walked by the patients showed a positive correlation with hemoglobin (r=0.461, 95% CI: 0.170- 0.678, p=0.002) and negative with reticulocytes count (r=-0.352, 95% CI:-0.601- - 0.041; p=0.023). Patients with moderate desaturation at rest had odds of increase 6.5-fold of post-test desaturation development (OR: 6.5; 95% CI: 1.47-28.71; p=0.021). When evaluating the patients in relation to the absence (G1) or presence (G2) of post-test desaturation (defined as decline O2≥3% from baseline), 14 (31.8%) of the individuals belonging to G2 were observed. Regarding the hemolytic biomarkers, G2 presented a lower HbF level (p=0.041), lower BMI (p=0.007), higher reticulocytes count (p=0.007) and DHL (p=0.002) compared with G1. Conclusion: It was detected a high prevalence of moderate desaturation at steady state as well as post 6MWT in adults with SCD. Desaturation was associated with elevation of hemolysis biomarkers, suggesting being associated with the greater severity of the disease. The detection of these abnormalities in the 6MWT underscores the importance of considering this non-invasive test as a means of monitoring patients with FD, although additional studies are needed to elucidate the role of 6MWT in adults with SCD.
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    Tendência secular da mortalidade e fatores associados ao óbito precoce por doença falciforme no estado de São Paulo
    (Universidade Federal de São Paulo (UNIFESP), 2021) Souza, Nayara Dorta De [UNIFESP]; Konstantyner, Tulio [UNIFESP]; Universidade Federal de São Paulo
    Objective: To estimate the trend in the mortality rate and the average age of death, and to identify the sociodemographic factors associated with early death in patients with sickle cell disease in the State of São Paulo. Methods: Descriptive and analytical ecological and transversal study, based on data from the Mortality Information System. All events of death of patients residing in the State of São Paulo from 01/01/1996 to 12/31/2015 were included, which contained at least one International Disease Code for Sickle Cell Disease in any field of the medical certificate. death. The trends in mortality rates (general and stratified by age group) and average age of death over the years were estimated using simple linear regression. For the investigation of factors associated with early death, which was defined when death ocurred before the median life expectancy of patients with DF, univariate and multivariate survival analyzes were performed, using Cox regression. The Kaplan Meier graph was used to represent univariate associations. Results: The overall mortality rate per million inhabitants increased by 0.084 per year (R² = 0.783 and p <0.001). When stratified by age group, in the age subgroup it was greater than 20 years, the increase was 0.108 per year (R² = 0.789 and p <0.001) and in those under 20 years it was 0.023 per year (R² = 0.188 and p = 0.056). The analysis of the trend of the average age at death showed an increase of 0.617 years per year analyzed (R² = 0.835 and p <0.001 In the multivariate analysis of the factors associated with early death, being male (HR = 1.30), white (HR = 1.16), dying inside the hospital (HR = 1.29) and living in Greater São Paulo (HR = 1.13) presented a higher risk of early death, when compared to the reference categories. Conclusion: During the 20 years analyzed, there was an increase in the mortality rate and the average age of death with Sickle Cell Disease. The sociodemographic factors: sex, race, place of occurrence and municipality of residence were associated with the age range of death.