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| Author(s): |
Lidiane de Souza Torres
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São José do Rio Preto. 2016-03-04. |
| Institution: | Universidade Estadual Paulista (Unesp). Instituto de Biociências Letras e Ciências Exatas. São José do Rio Preto |
| Defense date: | 2016-02-26 |
| Advisor: | Claudia Regina Bonini Domingos; Sonia Maria Oliani |
| Abstract | |
Sickle cell disease (SCD) is a hereditary hemolytic anemia caused by the presence of hemoglobin S (Hb S). In Brazil, the most common forms of SCD are the homozygous (Hb SS) and the association of Hb S with hemoglobins C (Hb SC), D-Punjab (Hb SD) and beta thalassemia (Hb Sβ-thal). Inflammation in SCD is a chronic condition, with the recurrent release of pro-inflammatory cytokines, and is related to hypoxic and angiogenenic events, which are characteristics of the disease. The behavior of these events in SCD genotypes could explain variations frequently found in the clinical manifestations of patients. Thus, the aim of the study was to verify the inflammation, hypoxia and angiogenesis processes in the Hb SS, Hb SD, Hb Sβ-thal and Hb SC genotypes of SCD, comparing the results to a control group without hemoglobinopathies. At first, the hemolytic profile of SCD individuals was evaluated considering the reticulocytes percentage and the lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and indirect bilirubin (IB) levels. The inflammatory profile was analyzed by quantifying the plasma levels of pro-inflammatory cytokines (IL-1β, IL-8, and TNF-α), anti-inflammatory proteins (TGF-β1 and ANXA1), responsive factors to hypoxia (HIF-1α and VEGF), and genetic polymorphisms able to influence the studied pathways. The percentage of reticulocytes and the LDH, AST, and IB levels were higher in the Hb SS genotype, followed by Hb SD, while the Hb Sβ-thal and Hb SC genotypes presented milder hemolytic profile. The plasma levels of inflammatory markers IL-1β, IL-8, TNF-α, and TGF-β1 were higher in SCD than in the control group, especially in the Hb SS genotype, demonstrating the presence of more severe inflammation in the group with greater hemolytic intensity. The ANXA1 was reduced in SCD, reflecting the imbalance between inflammatory response propagation and inflammation resolution, however, among the genotypes, ANXA1 was increased in the Hb SS group, suggesting its externalization as a compensatory mechanism for the resolution of inflammation in this group with greater clinical and inflammatory severity. HIF-1α also presented higher plasma levels in the SCD group, however, without distinction between the genotypes, while the plasma levels of VEGF were not increased in SCD, they are influenced by polymorphisms in its gene. With the obtained results, we conclude that inflammation is a present condition in all SCD genotypes with variable intensity and dependent upon the disease severity, which is higher in the Hb SS and Hb SD forms, and also related to the hypoxic and angiogenic processes. (AU) | |
| FAPESP's process: | 12/19653-1 - Genetic polymorphisms and markers expression involved in inflammatory processes, angiogenesis and hypoxia in sickle cell disease |
| Grantee: | Lidiane de Souza Torres |
| Support Opportunities: | Scholarships in Brazil - Doctorate |