Test Variability of the QuantiFERON-TB Gold In-Tube Assay in Clinical Practice John Z. Metcalfe, Adithya Cattamanchi1, Charles E. McCulloch, Justin D. Lew, Ngan P. Ha, and Edward A. Graviss Am J Respir Crit Care Med Vol 187 : 206-211, Jan, 2013 R3 이태인

Backgrounds QuantiFERON-TB Gold In-Tube (QFT-GIT) is a commercially available IGRA that has been recommended as an alternative to the TST Limited data on the precision of IGRA results Repeatability & reproductibility Multiple independent studies support a greater amount of test variability than that reported by the manufacturer

To improve the clinical interpretation of GFT-GIT results, particularly results the cut-point for a positive test, repeatability was analyzed in a low TB incidence setting

Methods – study population From August 1, 2010 to July 31, 2011 Internal quality control algorithm Low incidence of TB infection QFT-GIT testing was repeated using leftover stimulated plasma Excluded individuals with low TB response(<0.25 IU/ml) and low nil control(<0.10 IU/ml)

Methods – data collection According to the manufacturer’s instructions using identical instrument settings Repeated using leftover stimulated plasma A second round of retesting in duplicate(test 3,4) if the first two tests were discordant

Results

Disscussion There is a substantial and clinically important variability in GFT-GIT results on retesting Higher than that initially reported by the manufacturer Important implications for interpretation of borderline test results and conversion-reversion thresholds for screening

Variability inherent to the test rather than host or pathogen factors “Low positive zone”

Previous literatures documenting variable amounts of GFT-GIT imprecision and calls for borderline zones of various ranges Traditionally been determined by dividing the pooled SD by the overall mean TB response Acount for the low variability reported by the manufacturer

Limitations Because most negative test results with TB response less than 0.25 IU/ml were not analyzed, the inherent variability of this group was not assessed Some potential sources of variability were not considered (e.g., operator-dependent variability)

Conclusion QFT-GIT has a normal expected range of within-subject test variability of ±0.60 IU/ml overall, and ±0.24 IU/ml among subjects with borderline TB response near the manufacturer-recommended cut-point (0.25~0.80 IU/ml) Low-risk individuals with a positive QFT-GIT results less than 0.59 IU/ml should be interpreted cautiously