Relação entre os marcadores de inflamação e hemólise com a mutação em GATA-1 na doença falciforme

Abstract

Sickle cell disease is characterized by mutations present in the β-globin gene, containing at least one βs

allele which, when in homozygosity, identifies sickle cell anemia (HbSS). The pathophysiology of sickle cell disease begins with the polymerization and depolymerization of HbS, a process responsible for the initial changes in the erythrocyte membrane. Subsequently, a series of molecules and cells are recruited, expressed, and activated, both in the red blood cell membrane and in endothelial cells and circulation, generating a cascade of reactions and events responsible for the establishment of a chronic inflammatory process. One factor that may interfere with this inflammatory process, is the Duffy null phenotype. This phenotype results from a point mutation in the GATA-1 erythroid promoter box, leading to the silencing of Fyb

antigen expression on the erythrocyte surface, which, when present, acts as a receptor for pro-inflammatory chemokines, participating in the modulation of the inflammatory response. Thus, the present study aimed to identify the influence of the GATA-1 mutation on the inflammatory process of sickle cell individuals. Genotyping was performed for the FY*01, FY*02, and FY*02N.01 alleles in samples

from sickle cell individuals and healthy blood donors, in addition to measuring C- reactive protein (CRP), interleukin-8 (IL-8) and interleukin-1β (IL-1β) as inflammation

markers, and lactate dehydrogenase (LDH) as a marker of hemolysis. The results showed that the mutated allele FY*02N.01 is found at a frequency almost twice higher in sickle cell individuals than in individuals without the disease. Regarding inflammation and hemolysis markers, CRP, IL-8 and LDH presented significant differences between sickle cell individuals and donors, with the highest levels found in the former group. No statistical difference was identified in the levels of IL-1β between the groups. The use of hydroxyurea by sickle cell disease patients did not show interference in the levels of the analyzed interleukins, with differences only identified in the levels of CRP and LDH with the medication's use. The GATA-1 mutation in homozygosity seemed to have an influence only on IL-8 levels in sickle cell individuals. From these results, it is concluded that sickle cell individuals present chronic inflammation, even when clinically stable, and the presence of the mutated allele may lead to increased serum levels of IL-8, contributing to the maintenance of the inflammatory process in these individuals.