Screening and identification of a six-cytokine biosignature for detecting TB infection and discriminating active from latent TB

Abstract

[...]for various candidates [19], most of the data from these studies are preliminary and need further validation in ongoing multi-cohort studies, especially in a clinically oriented setting in highly TB-endemic regions, which include subjects with different clinical conditions. According to the pre-established case definitions, 91 of the recruited patients were finally diagnosed as ATB (only 25 patients had a positive culture for Mtb, 35 patients had a positive AFB smear, and 31 patients were positive for both). [...]PBMCs from BCG-vaccinated subjects may exhibit a strong cross-reaction when treated with PPD, which will lead to a false positive result. [...]the RD1 encoded ESAT-6 and CFP-10, being absent from BCG strains and most non tuberculous mycobacteria, were chosen as antigens in our cytokine release assays to improve the diagnostic specificity [6, 23]. Since SVM were used for the selection of biomarkers that resulted in the highest classification accuracy, the selection indicated that TB antigen stimulated IP-10 and IL-1Ra contributed more to the predictive value of the multi-cytokine signature than IL-2 and MCP-1 [21, 29].