Estudo das variantes no gene HLA-G de pacientes com anemia falciforme atendidos na Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas – HEMOAM

Abstract

Introduction: Sickle cell anemia is the most common hereditary hemolytic disease in the world, mainly affecting people of African descent, and is considered a public health issue. The hemoglobin present in the extracellular medium, resulting from hemolysis in the disease, is recognized by the immune system, which can recruit cells and generate chronic, sterile inflammation, which can cause obstruction of blood vessels. HLA-G is a class I molecule of the major histocompatibility complex with tolerogenic properties, which can inhibit both innate and adaptive immunity. The soluble isoforms of HLA-G produced by leukocytes have been implicated in various immunoregulatory functions and research indicates that levels of soluble HLA-G are elevated in a significant proportion of patients with sickle cell anemia, both during steady states and after recent crises. Genetic variants of this protein have been observed to influence susceptibility to infections, which is relevant due to the increased risk of pre-existing infections in patients with sickle cell anemia. Objective: To analyze the impact of SNVs in the HLA-G gene and their correlation with the expression of the soluble portion in patients with sickle cell anemia and healthy blood donors. Methodology: 85 patients with sickle cell anemia were recruited and blood was collected in EDTA tubes. The blood counts of these patients were taken and the SNVs rs1049033, rs9380142 and rs1710 of the HLA-G gene were genotyped by real-time PCR, and the soluble HLA-G was quantified by sandwich ELISA according to the manufacturer's protocol (ThermoFisher). Results: The study included 85 patients with sickle cell anemia (44 in steady state and 41 in vaso-occlusive crisis), as well as 80 healthy individuals as a control group. Patients in crisis had significantly lower hemoglobin and hematocrit levels, and higher leukocyte and neutrophil counts. In the genetic analysis, the C/T genotype of the rs1049033 variant was more frequent in the cases than in the controls. There was a significant increase in the levels of sHLA-G analyzed in the vaso-occlusive crisis group compared to the control group. Conclusion: The findings of this study corroborate the literature by demonstrating hematological alterations compatible with the different clinical stages of PA, as well as pointing to the potential role of the rs1049033 HLA-G gene variant in the immune modulation of the disease. The significant elevation of sHLA-G in the patients suggests that this molecule may be part of a compensatory mechanism for inflammation, reinforcing its relevance as a possible immunological marker.