THE IL-17F rs763780 SNP IS ASSOCIATED WITH HUMAN TUBERCULOSIS SUSCEPTIBILITY AND DISEASE SEVERITY IN ARGENTINA.

AGUSTÍN ROLANDELLI; JOAQUIN M. PELLEGRINI; SANTILLI CECILIA; AMIANO, NICOLÁS; CASTELLO, FLORENCIA A.; MARÍA PAULA MORELLI; NANCY TATEOSIAN; CASCO, NICOLÁS; ALBERTO LEVI; DOMINGO J. PALMERO; GARCÍA, VERÓNICA E.

Congreso; Reunión Conjunta de Sociedades de Biociencias 2017; 2017

Mycobacterium tuberculosis (Mtb) causes nearly 10 millions of new tuberculosis disease cases annually. However, most individuals exposed to Mtb do not develop tuberculosis, suggesting the influence of a human genetic component. In this work, we investigated the association of the IL-17F rs763780 SNP (TC), which generates a protein that is a natural IL-17F antagonist, with tuberculosis disease in Argentina. We found that individuals carrying the C allele were overrepresented in the TB population (TB N=201; HD N= 200; p<0.001). Strikingly, we found that Mtb-stimulated PBMCs of HD secreted higher amounts of IL-17F than Mtb-stimulated PBMCs of TB (p<0.01), but we did not found any differences in the IL17F secretion between individuals carrying the different genetic variants. We also observed that Mtb-stimulated PBMCs of HD carrying the C allele produced the lowest levels of IFN- in culture supernatants (p<0.05), percentage of CD4+ T cells producing IFN-(p<0.05) and the lowest proliferation index (p<0.05), indicating that these individuals would mount a poorer immune response against the bacterium. Within the TB population, Mtb-stimulated PBMCs of patients with the poorest immune response against the bacteria displayed the lowest level of IL-17F in culture supernatants (p<0.01). Moreover, we detected the lowest levels of IFN- (p<0.001) and highest levels of IL-17A (p<0.05) in culture supernatants of Mtb-stimulated PBMCs of TB carrying the C allele; and we measured the highest percentage of IL-17A producing CD4+ T lymphocytes (p<0.05) and the lowest proliferation index (p<0.05), immunological parameters associated with the disease severity. In fact, we evidenced that the majority of the patients carrying the C allele had a greater number of bacilli in sputum smears than patients carrying the TT genotype (p<0.01). Therefore, the C allele of the IL-17F rs763780 SNP is proposed as a marker of tuberculosis susceptibility and disease severity in Argentina.