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dc.contributor.authorSilva Junior, Alexander Leonardo-
dc.date.available2022-07-25-
dc.date.available2022-08-08T16:35:36Z-
dc.date.issued2020-11-16-
dc.identifier.urihttp://repositorioinstitucional.uea.edu.br//handle/riuea/4069-
dc.description.abstractIntroduction: Sickle cell disease is the most common monogenic disorder around the world. The mutation leads to a shift on hemoglobin molecule, which takes to hemolysis condition, marked mainly during acute inflammatory crisis and characterized by immune system activation. The molecule participation as chemokines, anaphylatoxins, cytokines and growth factors released specially by leukocytes and endothelial cells increase the risk to develop vaso-occlusive crisis and so, the clinical complications observed in these patients. Due to immune molecule influence on sickle cell physiopathology, under different clinical status, related to scarcity of biomarkers studies, we highlight the need to characterize the concentration of these proteins on inflammatory state of sickle cell. Objective: Evaluate the immunological profile of patients with sickle cell anemia under different clinical status accompanied at Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM). Materials and methods: This is a longitudinal study which used biological samples of 53 healthy blood donors, 27 patients with sickle cell anemia in steady-state condition, 22 patients in acute vaso-occlusive crisis, in which were accompanied with one more sample collection, at convalescence. The samples were from previous projects approved by CEP-HEMOAM. The blood count was performed with whole blood, while serum was used to quantification of cytokines, chemokines and growth factors by Luminex technic, with the kit BioPlex Pro-Human Cytokine 27-Plex from BioRad at FIOCRUZ-MG and analyzed by BioPlex Manager software. Anaphylatoxins were measured at Fundação HEMOAM by Cytometric Bead Array technic, with kit The BD CBA Human Anaphylatoxin, and FCAP Array software was used for acquisition. Statistical analysis was performed on GraphPad Prism v. 5.0 software, with confidence interval of 95% and p < 0.05 as statistically significant. Correlation network was performed on software Cytoscape v. 3.1. and heatmaps on software R 3.0.1. Results: We identified higher concentration of IL-2, IL-4, IL-5, IL-7, PDGF-BB and G-CSF on vaso-occlusive patients, which further demonstrates a biomarker signature to this clinical condition. Other molecules showed different concentration under clinical profile, but were not exclusive only to crisis status. IL-10, IL-1ra and IL-1β concentration were identified by bioinformatics technics as potential markers to cluster patients under clinical condition. In convalescence condition, CXCL8, CCL4, IL-1ra and PDGF-BB showed potentiality as laboratorial markers of follow-up after crisis. Correlation analysis showed higher relation of molecules in crisis condition, which reduced through convalescence until steady-state. Conclusion: Vaso-occlusive crisis profile is marked by anti-inflammatory and cell proliferation cytokines. IL-1ra and PDGF-BB are potential candidates as laboratorial markers to laboratorial recovery, and serum concentration of IL-10, IL-1ra and IL-1β might be used to characterize the clinical status of sickle cell patient. More studies must be conducted to evaluate the potentiality of these molecules on clinical progression, on prognosis and follow- up of these patients after crisis.pt_BR
dc.languageporpt_BR
dc.publisherUniversidade do Estado do Amazonaspt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectMoléculaspt_BR
dc.subjectAnemia Hemolíticapt_BR
dc.subjectAmazônia Brasileirapt_BR
dc.subjectPerfil Imunept_BR
dc.titleAvaliação do perfil de biomarcadores imunológicos no perfil clínico de pacientes com anemia falciformept_BR
dc.typeDissertaçãopt_BR
dc.date.accessioned2022-08-08T16:35:36Z-
dc.contributor.advisor-co1Paula, Erich Vinicius de Paula-
dc.contributor.advisor-co1Latteshttp://lattes.cnpq.br/0983518713985469pt_BR
dc.contributor.advisor1Marie, Adriana Malheiro Alle-
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/2627415957053194pt_BR
dc.creator.Latteshttp://lattes.cnpq.br/8588604910962305pt_BR
dc.description.resumoIntrodução: A anemia falciforme é a doença monogênica de maior frequência no mundo. A mutação causa uma mudança na molécula de hemoglobina, que leva a um quadro de hemólise, acentuado em crises agudas de inflamação e caracterizado pela ativação do sistema imunológico. A participação de moléculas como quimiocinas, anafilotoxinas, citocinas e fatores de crescimento liberadas principalmente pelos leucócitos e células endoteliais aumenta o risco de desenvolver crises vaso-oclusivas e assim, as complicações clínicas observadas nesses pacientes. Devido à atuação das moléculas imunes na fisiopatologia falciforme, em diferentes quadros clínicos, ligado à escassez de estudos de biomarcadores, salienta-se a necessidade de caracterizar a concentração destas proteínas no estado inflamatório da anemia falciforme. Objetivo: Avaliar o perfil de moléculas imunológicas em pacientes com anemia falciforme em diferentes estados clínicos acompanhados na Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM). Material e métodos: Este é um estudo longitudinal que utilizou amostras biológicas de 53 doadores saudáveis, 27 pacientes com anemia falciforme em estado estacionário e 22 em crise aguda vaso-oclusiva, sendo estes últimos acompanhados com mais uma coleta, na fase de convalescença. As amostras foram provenientes de projetos já aprovados pelo CEP-HEMOAM. O hemograma foi realizado em analisador automatizado com amostras de sangue total, enquanto o soro foi utilizado na quantificação de citocinas, quimiocinas, fatores de crescimento pela técnica de Luminex, pelo kit The BioPlex Pro-Human Cytokine 27-Plex da BioRad na FIOCRUZ-MG e analisadas pelo software BioPlex Manager. As anafilotoxinas foram dosadas na Fundação HEMOAM pela técnica de Cytometric Bead Array, com o kit The BD™ CBA Human Anaphylatoxin e para aquisição foi utilizado o software FCAP Array. A análise estatística foi realizada no software GraphPad Prism v. 5.0, com intervalo de confiança de 95% e valor de p < 0.05 como estatisticamente significativo. A rede de correlação foi feita no software Cytoscape v.3.1 e os heatmaps no software R 3.0.1. Resultados: Identificamos maior concentração de IL-2, IL-4, IL-5, IL-7, PDGF-BB e G-CSF nos pacientes em crise vaso-oclusiva, que posteriormente demonstraram uma assinatura de biomarcadores para esta condição clínica. Outras moléculas apresentaram diferenças entre os perfis clínicos, mas não foram exclusivas apenas para o grupo de crise. A concentração de IL-10, IL-1ra e IL-1β foram identificadas por técnicas bioinformáticas com potencial para caracterizar os pacientes entre os estados clínicos. Na fase de convalescença, a CXCL8, CCL4, IL-1ra e PDGF-BB se mostraram potenciais marcadores de acompanhamento laboratorial após a crise. A análise da correlação mostrou maior relação das moléculas entre si no estado de crise, que tende a reduzir através da fase de convalescença, até o estado estacionário. Conclusão: O perfil de crise é marcado por citocinas anti-inflamatórias e de proliferação celular. IL-1ra e PDGF-BB são potenciais candidatos para marcadores de recuperação laboratorial, e concentração sérica de IL-10, IL- 1ra e IL-1β podem ser utilizados para caracterizar o estado clínico do paciente falciforme. Mais estudos devem ser conduzidos para avaliar o potencial destas moléculas na progressão clínica, no prognóstico e no acompanhamento dos pacientes após a crise.pt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.programPPGH -PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIApt_BR
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