Avaliação de variantes de nucleotídeo único (SNV) em genes do sistema HLA em pacientes com tuberculose

Abstract

Infectious diseases tuberculosis (TB) continue to be a major cause of death worldwide. After COVID-19, TB was the second leading cause of death worldwide due to a single infectious agent. TB is caused by species of Mycobacterium tuberculosis complex and presently it is still considered a global threat and a serious public health problem. As per the World Health Organization in 2022, an estimated 10,6 million people fell ill and 1,30 million died of TB in the country. The national context, the state of Amazonas (84,1 cases/100 thousand inhabitants) and Manaus (115,8 cases/100 thousand inhabitants) recorded the highest TB incidence coefficient in Brazil. The high rates presented in the region intrigue us to investigate the reasons for this. Furthermore, another curious fact is that around 5-10% of individuals infected develop the active disease. The mechanisms involve mycobacterium-host interaction are interesting targets of study because the innate and adaptive immune system mount responses to eliminate the pathogen. In this context, there is a conjunct of genes located in the HLA (Human Leukocyte Antigen) system which encode related proteins to the presentation of antigens, connects innate and adaptive immune responses, immune signaling and regulation and synthesis of complement proteins. Considering the TB is a multifactorial disease and host genetic factors such as Single-Nucleotide Variants (SNV) have been associated with different clinical outcomes and individual variability in the presence of the pathogen, the research aims to evaluate SNV in different genes located the HLA system (rs9271300 in gene HLA-II, rs1049033 e rs1632937 in HLA-G e o rs1051792 in MICA) and relationship with concentration of cytokine IL-6, IL-1β, IFN-γ and TNF-α in patients with TB in the State of Amazonas. A total of 1275 samples have been analyzed being 150 patients with extrapulmonary TB (TBe), 531 patients with pulmonary TB (TBp) and 594 controls recruited from the Policlínica Cardoso Fontes in the city of Manaus. The qPCR technique (Quantitative Real Time PCR) was used for genotyping the samples. Quantification of cytokines will be done by the ELISA technique (Enzyme Linked Immunosorbent Assay) in plasma samples. Of the analyzed samples, it was observed is associated with protection for TBe (p=0,0307; OR=0,54) e TBp (p=0,0110; OR=0,55) of the SNV rs9271300 and AA genotype of SNV rs1051792 is associated with increased risk for TBe (padj=0,0069; OR=1,85). SNV rs1049033 and rs1632937 located in the HLA-G gene no association was observed between the study groups. In general, serum IL-1β, IFN-γ and TNF-α concentrations were higher in patients with TB than those in Controls. IL-6 concentrations were similar in both the case and control populations. Therefore, the results of this study can contribute to a better clarification of the mechanisms involved in the outcome of TB, especially in our Amazonian population.