Caracterização do polimorfismo do gene MBL2 em pacientes com leucemia linfoide aguda

Abstract

Mannose-binding lectin (MBL) is an acute phase plasma protein of innate immunity, with effector and regulatory properties that play a key role in host defense against pathogenic microorganisms. MBL exerts its activity through the activation of the complement system, mechanisms of opsonization and phagocytosis, through its ability to bind to carbohydrates rich in mannose, fucose and glucosamine, present on the cell surface of several pathogenic microorganisms. However, the presence of genetic variants in exon 1 of the MBL2 gene are associated with low plasma concentrations of the protein. These variations can result in greater susceptibility to infections, especially in immunosuppressed individuals. The main objective of this study was to characterize the polymorphism of the MBL2 gene and to evaluate the possible association of genotypes and serum levels of the MBL protein with susceptibility to infections in patients with Acute Lymphoid Leukemia (ALL). A total of 122 patients with ALL treated at foundation HEMOAM were included in this study. Genotyping of exon 1 of the MBL2 gene was performed using the PCR and restriction enzyme digestion (RFLP) technique, followed by measurement of plasma levels of MBL using an immunoenzymatic assay (ELISA). The results revealed a higher frequency of the MBL*A allele (0.37) in this study population, while the MBL*D allele (0.32) was the most frequent among the variant alleles, followed by the MBL*B allele (0.31) . The MBL*C allele was not found. However, when considering the frequency of the O polymorphic allele (presence of B or D) a frequency of 0.68 was observed. The A/O genotype (0.49) was the most common and its carriers had the highest number of infections, followed by the O/O genotype (0.38) and the A/A genotype (0.13). In the period from 2015 to 2023, a total of 239 infections occurred in the study population. The most frequent infections were parasitic (n=103) and bacterial (n=69). In addition, viral (n=48) and fungal (n=19) infections were also observed. However, no significant associations were observed between MBL serum levels, types of genotypes and susceptibility to infections. This study presents the first description of the genetic variability of the MBL2 gene in patients with ALL and its association with susceptibility to infections. The results obtained contribute to a better understanding of the genetic basis of the immune response and its relationship with health and disease in the context of ALL