Multicytokine Detection Improves Latent Tuberculosis Diagnosis in Health Care Workers

Beyond the IFN-γ horizon: biomarkers for immunodiagnosis of infection withMycobacterium tuberculosis

“…Two studies in adult household contacts compared with cases with active tuberculosis concluded that IP-10 detects a similar number of exposed individuals as IGRAs [117,118] and have comparable increases in test positivity with increasing age in the population [118]. A French study in healthcare workers, found IP-10 positive in all eight QFT positive, and in 32% of 41 healthcare workers with negative QFT and positive TST [69]. Similar discordance was observed in a Chinese study of 73 healthy household contacts.…”

“…Case-control studies comparing adult patients with active tuberculosis to healthy controls, suggest that IL-2 has comparable sensitivity for active TB and specificity in unexposed controls as IFN-c and IP-10 [60,82,102,103]. A similar ability has also been shown for presumed latent infection defined by both IGRA/TST response [69,94] and exposure gradient [102,103]. In contrast, other studies suggest that IL-2 expression is lower in patients with tuberculosis compared to latently infected individuals and controls [98,104], this will be discussed in detail later.…”

“…In this study, IP-10 classified 56% CXCL: chemokine (C-X-C motif) ligand; IL: interleukin; MIG: monokine induced by interferon-c; IP-10: interferon-c-induced protein 10; MCP: monocyte chemotactic protein; MIP: macrophage inflammatory protein; IFN: interferon; TNF: tumour necrosis factor; EGF: epidermal growth factor; TGF: transforming growth factor; VEGF: vascular endothelial growth factor; sCD40L: soluble CD40 ligand; IL-1RA: IL-1 receptor antagonist. Several markers showed no or only little diagnostic potential including GRO (CXCL1) [60], stromal cell-derived factor 1 (CXCL12) [97], Fractalkine (CXC3CL1) [65,89], I-309 (chemokine (C-C motif) ligand (CCL) 1) [97], regulated on activation, normal T-cell expressed and secreted (CCL5) [62,69,86], eotaxin (CCL11) [62,65,69] [70] explored the diagnostic potential using ESAT-6/CFP10 stimulated PBMCs, and found it less sensitive for active tuberculosis compared to IFN-c; similar results were recently shown in a whole blood model [62]. Other studies demonstrated comparable performance to IP-10 and IFN-c in patients with active tuberculosis compared to controls [67] and in healthcare workers with presumed LTBI [69].…”

IP-10 and MIG Are Compartmentalized at the Site of Disease during Pleural and Meningeal Tuberculosis and Are Decreased after Antituberculosis Treatment

“…Cutoffs for antigen-specific IP-10, MIG, IL-6, and SDF-1 were estimated at various sensitivities and specificities. To avoid false-positive results, a cutoff value corresponding to the maximum Youden index, defined as sensitivity ϩ specificity Ϫ 1, was retained (23). Optimal cutoff levels for differentiating individual groups were determined by ROC curve analysis, based on the highest likelihood ratio.…”

IFN-γ release assay versus tuberculin skin test for monitoring TB infection in healthcare workers

“…Studies that try to identify additional biomarkers for LTBI are currently being performed [95]. Whether these potential new biomarkers will be able to distinguish recent from remote LTBI remains to be seen.…”