Table 3.
Summary of diagnosticc biosignatures identified in this study.
| Biosignature(i) obtained when all host markers (n = 12) were considered; implying limited numbers of study participants (N = 251), from 4 sites only, regardless of HIV status | ||||||
|---|---|---|---|---|---|---|
| Training set (N = 176, n = 75 TB, n = 101 ORD) | Test set (n = 75, n = 32TB; n = 43ORD) | |||||
| Biosignature (i) a | Sensitivity | Specificity | Sensitivity | Specificity | PPV | NPV |
| IFN-γN, TGF-αN, IL-1RaAg-N, MIP-1βAg-N | 70.7% (58.9–80.3) | 81.2% (71.9–88.0) | 68.8%(50.0–83.3) | 76.7%(61.0–87.7) | 68.8%(50.0–83.3) | 76.7%(61.0–87.7) |
| Biosignature (ii) obtained when all study participants (n = 445*, all sites) were considered, implying limited numbers of markers (n = 9) | ||||||
| Biosignature (ii) | Training set (n = 311; n = 122 TB, n = 189 ORD) | Test set (N = 134; n = 53 TB; n = 81 ORD) | ||||
| IFN-γN, MIP-1βN, TGF-αN, TGF-αAg-N, VEGFAg-N | 68.9%(59.7–76.5) | 83.1%(76.8–88.0) | c64.2%(49.7–76.5) | d82.7%(72.4–89.9) | 70.8%(55.7–82.6) | 77.9%(67.4–85.9) |
| Biosignature (iii) obtained when all host markers (n = 12) were considered in HIV negative study participants only; implying limited numbers of study participants (N = 189), from 4 study sites | ||||||
| Biosignature (iii) | Training set: N = 133; n = 48 TB, n = 85 ORD | Test set: N = 56; n = 20 TB, n = 36 ORD | ||||
| IFN-γN, IFN-αN, sCD40LN, IL-1αN, MMP-2N, MMP-9N, IFN-α2Ag-N | 81.2%(66.9–90.6) | 81.2%(70.9–88.5) | 50.0%(27.9–72.1) | 83.3%(66.5–93.0) | 62.5%(35.9–83.7) | 75.0(58.8–86.8) |
| Biosignature (iv) obtained when all HIV negative participants (n = 352*, all sites) were considered, implying limited numbers of markers (n = 9) | ||||||
| Biosignature (iv) | Training set (N = 247; n = 92 TB, n = 155 ORD) | Test set (n = 105; n = 39 TB, n = 66 ORD) | ||||
| IFN-γN, TGF-αN, IL-1αN, MMP-2N, EGFAg-N, VEGFAg-N, TGF-α Ag-N | 73.9%(63.5–82.3) | 84.5%(77.6–89.6) | 51.3%(35.0–67.3) | 77.3%(65.0–86.3) | 57.1%(39.5–73.2) | 72.9%(60.7–82.4) |
All host markers were not evaluated at all study sites: IL-1ra and IFN-α2 were not evaluated on KPS, MRCG, and UCRC samples, whereas TNF-α was additionally not evaluated on MRCG samples for technical reasons. The GDA modelling procedure was therefore performed twice.
*Individuals with questionable TB status (see Table 1) were excluded.
aThe sensitivity of biosignature (i) increased to 81.3% and specificity decreased to 56.0% when the biosignature was optimized for high sensitivity. bThe sensitivity of biosignature (ii) increased to77.4% and specificity decreased to 60.5% when the biosignature was optimized for high sensitivity. N = Unstimulated (nil) value, Ag-N = antigen-specific response obtained after subtraction of nil from antigen-stimulated value.