Association of the IL-17A rs2275913 single nucleotide polymorphism with tuberculosis severity in Argentina

AGUSTÍN ROLANDELLI; RODRIGO HERNANDEZ DEL PINO; JOAQUIN M. PELLEGRINI; NANCY TATEOSIAN; NICOLÁS O. AMIANO; MORELLI, MARIA PAULA; FLORENCIA CASTELLO; NICOLAS CASCO; ALBERTO LEVI; DOMINGO J. PALMERO; VERÓNICA E. GARCIA

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Inmunología; 2016

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. Previously, we investigated the association of the rs2275913 SNP (GA) from IL-17A and tuberculosis in Argentina, and found an association between the AA genotype and tuberculosis resistance. In this work, we evaluated the functional relevance of this SNP during the immune response of the host against Mtb and analyzed its impact on clinical parameters of the disease severity. Thus, peripheral blood mononuclear cells (PBMCs) from GG, GA and AA healthy donors (HD) and tuberculosis patients (TB) were obtained and stimulated for five days with a Mtb lysate (Mtb-Ag), and IL-17A and IFN- production were measured by ELISA and Flow Cytometry. Our findings indicated that, within the HD population, AA cells produced the highest amounts of IL-17A (p<0.05) and IFN- (p<0.05), supporting the genetic evidence we have previously found. In contrast, within the TB population, AA Mtb-Ag stimulated cells produced the highest amounts of IL-17A (p<0.05) but the lowest levels of IFN- (p<0.05). Furthermore, AA patients showed the lowest proliferation index in Mtb-Ag stimulated PBMCs (p<0.05) and the lowest SLAM expression on CD3+ T cells (P<0.05), two immunological parameters that suggest a relationship with tuberculosis severity. In fact, we found an association between the AA genotype and clinical parameters of disease severity, such as severe radiological lesions (p<0.05) and higher AFB in sputum smear (p<0.05). Overall, our present results evidenced that the rs2275913 SNP could be a biomarker of resistance to tuberculosis and disease severity in the Argentinean population.