Banca de DEFESA: CAROLINE CONCEIÇÃO DA GUARDA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : CAROLINE CONCEIÇÃO DA GUARDA
DATA : 29/11/2019
HORA: 14:00
LOCAL: Auditório Aluízio Prata - IGM/FIOCRUZ
TÍTULO:

Sickle cell disease: laboratory and inflammatory biomarkers associated with clinical manifestations and use of hydroxyurea

PALAVRAS-CHAVES:

sickle cell anemia, sickle cell disease, inflammation, laboratory biomarkers, clinical manifestations

PÁGINAS: 179
GRANDE ÁREA: Ciências da Saúde
ÁREA: Farmácia
RESUMO:

Sickle cell disease (SCD) is a group of hemoglobinopathies and sickle cell anemia (SCA), characterized by HbSS homozygous, is the most severe form, while SC hemoglobinopathy (HbSC) is milder. Clinical manifestations in SCD are heterogeneous, thus, laboratory and inflammatory biomarkers are very useful in the clinical practice. Several pathophysiological mechanisms were suggested as significant associations were found with clinical manifestations and systemic inflammatory involvement of the disease. Therapy for SCD is based on hydroxyurea (HU), capable to improve laboratory biomarkers as well as to reduce clinical manifestations. Therefore, the aim of the present study was to investigate laboratory and inflammatory biomarkers associated to clinical manifestations in SCD as well as HU therapy. This study was approved by the Institutional Research Board (CAAE: 52280015.1.0000.0048), laboratory analyses were carried by automated methods and patients were followed-up at the Bahia Hemotherapy and Hematology Foundation (HEMOBA). In the first manuscript we included 181 SCD patients (126 HbSS and 55 HbSC) and we compared the groups based on each genotype. Our results suggest that SCA individuals more prominent exhibit anemia, hemolysis, leukocytosis and inflammation as well as increased frequency of clinical manifestations, while HbSC individuals exhibit less hemolysis and clinical complications. In the second manuscript we investigated among the 126 SCA individuals the association between clinical manifestations and lipid profile. History of pneumonia was found to be associated with higher total cholesterol levels, leg ulcers were associated with decreased low density lipoprotein (LDL) and pain crises were associated with increased high density lipoprotein (HDL). We also found associations between total cholesterol, LDL and HDL levels with hemolysis biomarkers as well as HbF levels, which was confirmed by the correlation analyses between individuals with previous history of pneumonia and pain crises. In the third manuscript 43 SCA patients were included and we evaluated interleukin-8 (IL-8) plasma levels as well as the rs4073 polymorphism. We verified that individuals carriers of the A allele have increased IL-8 levels, which was also associated with biomarkers of inflammation and hemolysis. In addition, lower IL-8 levels were associated with previous history of splenomegaly. In the last manuscript we investigated the effect of HU treatment on monocytes of SCA patients. Thirty seven patients were included, 17 were undergoing HU therapy while 20 were not receiving the medication. Our results suggest that HU was capable to decrease monocyte counts in peripheral blood, decrease classical monocytes (CD14++CD16-) frequency and increase non-classical monocytes (CD14dimCD16+). HU also decreased TNF-α, IL-1β, IL-6 and tissue factor (TF) production by the monocytes, as well as their polyfunctionality. Monocytes producers of TF were found to be associated with vaso-occlusion, in addition, classical monocytes are responsible for multiple cytokine production. Our data corroborate with previous studies regarding inflammatory and clinical aspects of SCA, in addition new associations between physiopathological mechanisms, laboratory biomarkers and pro-inflammatory molecules were found.

MEMBROS DA BANCA:
Externo ao Programa - 2055299 - ANA LEONOR PARDO CAMPOS GODOY
Externo à Instituição - ISADORA CRISTINA DE SIQUEIRA - Fiocruz-Ba
Externo à Instituição - MARIA DA CONCEICAO CHAGAS DE ALMEIDA - Fiocruz-Ba
Presidente - 183.851.845-20 - MARILDA DE SOUZA GONCALVES - UNICAMP
Interno - 011.952.725-10 - NATALIA MACHADO TAVARES - UFBA
Externo à Instituição - THIAGO MARCONI DE SOUZA CARDOSO - Fiocruz-Ba