RESUMO
Tuberculosis (TB) remains a serious public health burden worldwide. TB is an infectious disease caused by the Mycobacterium tuberculosis Complex. Innate immune response is critical for controlling mycobacterial infection. NOD-like receptor pyrin domain containing 3/ absent in melanoma 2 (NLRP3/AIM2) inflammasomes are suggested to play an important role in TB. NLRP3/AIM2 mediate the release of pro-inflammatory cytokines IL-1ß and IL-18 to control M. tuberculosis infection. Variants of genes involved in inflammasomes may contribute to elucidation of host immune responses to TB infection. The present study evaluated single-nucleotide variants (SNVs) in inflammasome genes AIM2 (rs1103577), CARD8 (rs2009373), and CTSB (rs1692816) in 401 patients with pulmonary TB (PTB), 133 patients with extrapulmonary TB (EPTB), and 366 healthy control (HC) subjects with no history of TB residing in the Amazonas state. Quantitative Real Time PCR was performed for allelic discrimination. The SNV of AIM2 (rs1103577) is associated with protection for PTB (padj: 0.033, ORadj: 0.69, 95% CI: 0.49-0.97). CTSB (rs1692816) is associated with reduced risk for EPTB when compared with PTB (padj: 0.034, ORadj: 0.50, 95% CI: 0.27-0.94). Serum IL-1ß concentrations were higher in patients with PTB than those in HCs (p = 0,0003). The SNV rs1103577 of AIM2 appeared to influence IL-1ß release. In a dominant model, individuals with the CC genotype (mean 3.78 ± SD 0.81) appeared to have a higher level of IL-1ß compared to carriers of the T allele (mean 3.45 ± SD 0.84) among the patients with PTB (p = 0,0040). We found that SNVs of AIM2 and CTSB were associated with TB, and the mechanisms involved in this process require further study.
Assuntos
Proteínas de Ligação a DNA/genética , Resistência à Doença/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Tuberculose/etiologia , Alelos , Brasil , Proteínas Adaptadoras de Sinalização CARD/genética , Estudos de Casos e Controles , Citocinas/metabolismo , Feminino , Genótipo , Humanos , Masculino , Mycobacterium tuberculosis , Razão de ChancesRESUMO
The occurrence of tuberculosis with first-line multidrug resistance leads to the use of alternative medications, often at higher costs, longer treatment periods, and greater clinical complexity. Here, we report 3 patients with multidrug-resistant tuberculosis. One patient with human immunodeficiency virus died before the sensitivity test was performed. The early diagnosis of multidrug-resistant tuberculosis and appropriate treatment should be priorities of the National Tuberculosis Control Program in order to break the chain of transmission. In addition, the possibility of substituting the proportion method with more modern and faster techniques should be urgently evaluated.
O surgimento de resistência múltipla às drogas de primeira linha implica na utilização de fármacos de maior custo, com duração mais longa, maior complexidade e mais efeitos colaterais. Relatamos os casos de três pacientes com multirresistência primária aos tuberculostáticos. O portador de HIV evoluiu para óbito antes do resultado do teste de sensibilidade. Portanto, o diagnóstico precoce de tuberculose multirresistente e o tratamento adequado devem ser prioridades do Programa Nacional do Controle da Tuberculose, visando interromper a cadeia de transmissão. Além disto, é urgente que seja avaliada a substituição do método das proporções por técnicas mais modernas e mais rápidas.