ORIGINAL RESEARCH

Adaptive immunity and genetic aspects of tuberculosis in children

Plekhanova MA
About authors

Department of Pediatrics, Center of Continuing Professional Education and Retraining,
Omsk State Medical University, Omsk, Russia

Correspondence should be addressed: Maria Plekhanova
ul. Lenina, d. 12, Omsk, Russia, 644099; ur.liam@sulp-anid

About paper

Funding: this work was supported by the Russian Foundation for Basic Research (Grant ID 16-16-55001).

Received: 2017-09-24 Accepted: 2017-10-25 Published online: 2018-01-13
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Cell-mediated immunity and the cytokine interferon gamma (IFNγ) have an important role in promoting host resistance against tuberculosis-causing mycobacteria (TBM), but the exact mechanism of developing immunity against tuberculosis (TB) is unknown. In this work we evaluate the immune response in TB and the association between IFNG gene polymorphism rs2069705 (T-1488C) and the intensity of specific immune reactions in children. The study was conducted in 310 children below 18 years distributed into 3 groups: the TB group included 110 children with TB confirmed by medical evaluation; the LTB group consisted of 156 children with latent infection; and the NTB group was represented by 44 non-infected children. A few immunoassays and molecular-genetic tests were performed; specifically, we evaluated the immune status of patients and the distribution of genotypic frequencies of the studied polymorphism, in the context of previous vaccination against TB. The cell-mediated immune response was mild in children with LTB, while in children with TB inflammation showed signs of chronicity due to the lack of functional activity of immune cells (p < 0.05). We also measured IFN-γ synthesis induced by specific mitogens (PPD-L, CFP32B, Rv2660c, ESAT6, 85a and ESAT6-CFP10), only to detect attenuation of the immune response in patients with TB, which was associated with the heterozygous rs2069705 variant (p < 0.05). Children with homozygous TT and CC genotypes demonstrated a more pronounced immune response. Low effectiveness of the TB vaccine was shown to be associated with the heterozygous genotype (50 %), while its high effectiveness was associated with the homozygous T genotype (40 %), possibly indicating the protective role of the latter. Our findings suggest that the studied polymorphism (specifically, its heterozygous variant) can be a predictive marker of TB in children.

Keywords: tuberculosis, children, polymorphism, Mycobacterium tuberculosis, ESAT6, immune response, interferon gamma, antigen, PPD-L, CFP32B, Rv2660c, 85а, ESAT6-CFP10, IFNG

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