02359nas a2200397   4500000000100000008004100001653001200042653001700054653001700071653001700088653001400105100001400119700001500133700001800148700002000166700001100186700001300197700001300210700001500223700001200238700001500250700001500265700001100280700001800291700001200309700001600321700002200337700001300359700001200372700002300384245010200407300001100509490000700520520142000527022001401947       2016                            d10aAntigen10aBiosignature10aHost markers10aTuberculosis10adiagnosis1 aAwoniyi D1 aTeuchert A1 aSutherland JS1 aMayanja-Kizza H1 aHowe R1 aMihret A1 aLoxton A1 aSheehama J1 aKassa D1 aCrampin AC1 aDockrell H1 aKidd M1 aRosenkrands I1 aGeluk A1 aOttenhoff T1 aCorstjens P L A M1 aChegou N1 aWalzl G1 aAE-TBC consortium 00aEvaluation of cytokine responses against novel Mtb antigens as diagnostic markers for TB disease.  a219-300 v733 a<p><strong>OBJECTIVE: </strong>We investigated the accuracy of host markers detected in Mtb antigen-stimulated whole blood culture supernatant in the diagnosis of TB.</p>

<p><strong>METHODS: </strong>Prospectively, blood from 322 individuals with presumed TB disease from six African sites was stimulated with four different Mtb antigens (Rv0081, Rv1284, ESAT-6/CFP-10, and Rv2034) in a 24&nbsp;h whole blood stimulation assay (WBA). The concentrations of 42 host markers in the supernatants were measured using the Luminex multiplex platform. Diagnostic biosignatures were investigated through the use of multivariate analysis techniques.</p>

<p><strong>RESULTS: </strong>17% of the participants were HIV infected, 106 had active TB disease and in 216 TB was excluded. Unstimulated concentrations of CRP, SAA, ferritin and IP-10 had better discriminating ability than markers from stimulated samples. Accuracy of marker combinations by general discriminant analysis (GDA) identified a six analyte model with 77% accuracy for TB cases and 84% for non TB cases, with a better performance in HIV uninfected patients.</p>

<p><strong>CONCLUSIONS: </strong>A biosignature of 6 cytokines obtained after stimulation with four Mtb antigens has moderate potential as a diagnostic tool for pulmonary TB disease individuals and stimulated marker expression had no added value to unstimulated marker performance.</p>
  a1532-2742