Perspectivas genéticas e imunológicas da anemia falciforme

Abstract

Sickle Cell Anemia (SCA) is the most common chronic hereditary disease in Brazil, characterized by a point mutation in the β-globin (HBB) gene located on chromosome 11. This mutation leads to the substitution of glutamic acid by valine at position 6, resulting in the formation of hemoglobin S (HbS). Under deoxygenated conditions, HbS polymerizes, deforming red blood cells into a sickle shape, which impairs tissue oxygenation and leads to severe clinical manifestations. This study aimed to identify and update the main genetic and immunological perspectives involved in sickle cell anemia, highlighting the importance of molecular and immunological understanding of the disease for proper clinical management. The research was conducted through a narrative literature review with a qualitative approach, using databases such as SciELO, PubMed, Google Scholar, CAPES Portal, and MEDLINE. The analyzed studies show that the severity of the disease varies according to the genotype, being more severe in HbSS individuals. Modulating genes such as BCL11A and HBS1L-MYB influence the expression of fetal hemoglobin (HbF), which has a protective effect, while mutations such as UGT1A1 and genes related to oxidative stress affect the inflammatory response and clinical severity.From an immunological perspective, the functional loss of the spleen compromises defense against infections, especially those caused by encapsulated bacteria. Alterations in regulatory T and B cells have also been observed, contributing to impaired immunity. For this reason, expanded immunization protocols are essential to reduce infectious complications.It is concluded that sickle cell anemia is a complex genetic and immunological disease, whose manifestations depend on multiple molecular factors. Understanding these interactions is essential for the adoption of personalized therapeutic and preventive strategies, promoting a better quality of life for patients.