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Abstract
Current diagnostic tests for tuberculosis (TB) are not able to predict reactivation disease progression from latent TB infection (LTBI). The main barrier to predicting reactivation disease is the lack of our understanding of host biomarkers associated with progression from latent infection to active disease. Here, we applied an immune-based gene expression profile by NanoString platform to identify whole blood markers that can distinguish active TB from other lung diseases (OPD), and that could be further evaluated as a reactivation TB predictor. Among 23 candidate genes that differentiated patients with active TB from those with OPD, nine genes (CD274, CEACAM1, CR1, FCGR1A/B, IFITM1, IRAK3, LILRA6, MAPK14, PDCD1LG2) demonstrated sensitivity and specificity of 100%. Seven genes (C1QB, C2, CCR2, CCRL2, LILRB4, MAPK14, MSR1) distinguished TB from LTBI with sensitivity and specificity between 82 and 100%. This study identified single gene candidates that distinguished TB from OPD and LTBI with high sensitivity and specificity (both > 82%), which may be further evaluated as diagnostic for disease and as predictive markers for reactivation TB.
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1 Gonçalo Moniz Institute (IGM) / Fiocruz, Advanced Laboratory of Public Health (LASP), Salvador, Brazil
2 Barretos Cancer Hospital, R. Antenor Duarte Villela, Molecular Oncology Research Center, Barretos, Brazil (GRID:grid.427783.d) (ISNI:0000 0004 0615 7498)
3 Gonçalo Moniz Institute (IGM) / Fiocruz, Advanced Laboratory of Public Health (LASP), Salvador, Brazil (GRID:grid.427783.d)
4 Barretos Cancer Hospital, R. Antenor Duarte Villela, Molecular Oncology Research Center, Barretos, Brazil (GRID:grid.427783.d) (ISNI:0000 0004 0615 7498); University of Minho, Life and Health Sciences Research Institute (ICVS), Medical School, Braga, Portugal (GRID:grid.10328.38) (ISNI:0000 0001 2159 175X); ICVS/3B’s-PT Government Associate Laboratory, Guimarães, Portugal (GRID:grid.10328.38) (ISNI:0000 0001 2159 175X)
5 Fundação José Silveira, Salvador, Brazil (GRID:grid.10328.38)
6 University of California, Division of Infectious Diseases and Vaccinology, School of Public Health, Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878)
7 Gonçalo Moniz Institute (IGM) / Fiocruz, Advanced Laboratory of Public Health (LASP), Salvador, Brazil (GRID:grid.47840.3f)