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. 2014 Oct;11(8):1267-76.
doi: 10.1513/AnnalsATS.201405-188OC.

Reproducibility of interferon gamma (IFN-γ) release Assays. A systematic review

Saloua Tagmouti  1 , Madeline Slater, Andrea Benedetti, Sandra V Kik, Niaz Banaei, Adithya Cattamanchi, John Metcalfe, David Dowdy, Richard van Zyl Smit, Nandini Dendukuri, Madhukar Pai, Claudia Denkinger
Affiliations

Reproducibility of interferon gamma (IFN-γ) release Assays. A systematic review

Saloua Tagmouti et al. Ann Am Thorac Soc. 2014 Oct.

Abstract

Rationale: Interferon gamma (IFN-γ) release assays for latent tuberculosis infection result in a larger-than-expected number of conversions and reversions in occupational screening programs, and reproducibility of test results is a concern.

Objectives: Knowledge of the relative contribution and extent of the individual sources of variability (immunological, preanalytical, or analytical) could help optimize testing protocols.

Methods: We performed a systematic review of studies published by October 2013 on all potential sources of variability of commercial IFN-γ release assays (QuantiFERON-TB Gold In-Tube and T-SPOT.TB). The included studies assessed test variability under identical conditions and under different conditions (the latter both overall and stratified by individual sources of variability). Linear mixed effects models were used to estimate within-subject SD.

Measurements and main results: We identified a total of 26 articles, including 7 studies analyzing variability under the same conditions, 10 studies analyzing variability with repeat testing over time under different conditions, and 19 studies reporting individual sources of variability. Most data were on QuantiFERON (only three studies on T-SPOT.TB). A considerable number of conversions and reversions were seen around the manufacturer-recommended cut-point. The estimated range of variability of IFN-γ response in QuantiFERON under identical conditions was ±0.47 IU/ml (coefficient of variation, 13%) and ±0.26 IU/ml (30%) for individuals with an initial IFN-γ response in the borderline range (0.25-0.80 IU/ml). The estimated range of variability in noncontrolled settings was substantially larger (±1.4 IU/ml; 60%). Blood volume inoculated into QuantiFERON tubes and preanalytic delay were identified as key sources of variability.

Conclusions: This systematic review shows substantial variability with repeat IFN-γ release assays testing even under identical conditions, suggesting that reversions and conversions around the existing cut-point should be interpreted with caution.

Keywords: IFN-γ release assays; diagnostics; reproducibility; tuberculosis.

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Figures

Figure 1.
Figure 1.
Flow chart of the study selection process. The literature search identified a total of 2,559 citations. After contacting experts in the field, three additional abstracts were added. Twenty-six studies fulfilled our inclusion criteria. Quantitative results for individual test results were available from authors for 19 of 26 studies that evaluated QuantiFERON and were partially available from 1 study. IGRA = IFN-γ release assay; TB = tuberculosis.
Figure 2.
Figure 2.
Quality of included studies. The overall quality of the selected studies as assessed by the modified quality appraisal tool for studies of diagnostic reliability (QAREL) tool (16).
See this image and copyright information in PMC

Comment in

References

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