Avaliação de marcadores biológicos com potencial para detecção da evolução para doença em tuberculose

Abstract

Tuberculosis (TB) is an infectious disease acquired by inhalation of aerosols containing its etiologic agent, Mycobacterium tuberculosis. TB primarily affects the lungs and is the leading bacterial cause disease deaths worldwide. Yearly, in Brazil, 69.000 cases of TB are reported, with 4.600 of these cases evolving to death. In the course of this infection 90% of the cases remain as 'latent' asymptomatic, and approximately 10% of the infected individuals progress to disease. This study investigated parameters of immune and inflammatory response in 18 to 65 years old subjects of both genders, with different degrees of exposure to M. tuberculosis (non-exposed controls, TST < 5 mm, n= 30; individuals with latent TB, TST &#8805; 5 mm; patients with pulmonary tuberculosis, n= 22). Our results demonstrated a failure of the TST to detect all the M. tuberculosis-exposed individuals, and in 1/3 of the TST positive ones there was no specific IFN-γ or CXCL10 in vitro response to M. tuberculosis-specific antigens. A direct correlation between the IFN-γ e CXCL10 responses was observed in whole-blood cultures stimulated with these specific antigens. The combined use of these two markers allowed us to detect a positive test for M. tuberculosis-specific antigens in 94,4% of the patients. There were marked differences in blood leukocyte specific mRNA levels for CD64, Ras-associated GTPase, lactoferrin, PDL-1 and CXCL10, but not for OASL, when tuberculosis patients were compared to the two other volunteer groups. In the same way, the levels of expression for CD64 and CD163 were significantly more elevated in the neutrophils of patients in comparison with the other two groups of healthy volunteers. Taken together our observations suggest that using more than one biomarker increases the sensitivity and specificity of the methods for the detection of M. tuberculosis latent infection and tuberculosis.