Table 3 Summary of diagnosticc biosignatures identified in this study.

From: Africa-wide evaluation of host biomarkers in QuantiFERON supernatants for the diagnosis of pulmonary tuberculosis

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)

  1. 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.
  2. *Individuals with questionable TB status (see Table 1) were excluded.
  3. 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.
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