Combined evaluation of TBAg/M, IL22 and IL17 to predict LTBI progression

Tuberculosis (TB) remains a major health issue worldwide, with 10 million new cases and 1.6 million deaths in 2017. According to WHO, about one third of the world’s population is infected with M. tuberculosis (МТВ). The widely used interferon gamma-release assays (QFT,T-SPOT) do not differentiate between latent MTB infection (LTBI) and its active phase. Recently, multicytokine analysis, and TBAg/M ratio from T-SPOT were proposed to distinguish LTBI from active TB (ATB). Aim: To compare QFT TBAg/M, as well as IL17 and IL22 MTB-specific profiles in ATB and LTBI subjects. Materials and methods: Peripheral blood samples from QFT(+) asymptomatic subjects (LTBI,n=21) and QFT(+) active TB patients (ATB,n=12) were analyzed. IL17 and IL22 production were determined after 18h stimulation with CD4 and CD8-specific MTB peptides (Quiagen) by ELISA (Affymetrix). TBAg1/M(R1) and TBAg2/(R2) were calculated based on MTB-specific and PHA-stimulated IFN γ production (OD). Results: R1 and R2 did not differ between LTBI and ATB (р>0.05 for both). LTBI was associated with domination of IL22+ MTB-specific CD4 and CD8 T: (mean OD) 0.09vs. 0.07 (p>0.05) and 0.15vs.0.07 (p 0.05). In addition, ATB was differentiated by elevated IL17+ MTB-specific CD4 (0,11vs.0.05 (p Conclusions: IL22+ CD8 play a key role in limiting MTB infection while IL17+ CD4 participate in MTB-mediated inflammation. QFT TbAg/M combined with IL22 and IL17 may contribute to determine the risk of LTBI progression. Supported by research grant No13-1/14.12.2017, Bulgarian NSF