Tagmouti Saloua, Slater Madeline, Benedetti Andrea, Kik Sandra V, Banaei Niaz, Cattamanchi Adithya, Metcalfe John, Dowdy David, van Zyl Smit Richard, Dendukuri Nandini, Pai Madhukar, Denkinger Claudia
1 Division of Respirology.
Ann Am Thorac Soc. 2014 Oct;11(8):1267-76. doi: 10.1513/AnnalsATS.201405-188OC.
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.
Knowledge of the relative contribution and extent of the individual sources of variability (immunological, preanalytical, or analytical) could help optimize testing protocols.
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.
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.
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.
在职业筛查项目中，用于潜伏性结核感染的干扰素γ（IFN-γ）释放检测出现转换和逆转的数量超出预期，检测结果的可重复性令人担忧。
了解个体变异来源（免疫、分析前或分析）的相对贡献和程度有助于优化检测方案。
我们对截至2013年10月发表的关于商用IFN-γ释放检测（QuantiFERON-TB Gold In-Tube和T-SPOT.TB）所有潜在变异来源的研究进行了系统评价。纳入的研究评估了相同条件下和不同条件下（后者包括总体以及按个体变异来源分层）的检测变异性。采用线性混合效应模型估计受试者内标准差。
我们共识别出26篇文章，包括7项在相同条件下分析变异性的研究、10项在不同条件下随时间重复检测分析变异性的研究以及19项报告个体变异来源的研究。大多数数据来自QuantiFERON（仅有三项关于T-SPOT.TB的研究）。在制造商推荐的切点附近可见相当数量的转换和逆转。在相同条件下，QuantiFERON中IFN-γ反应变异性的估计范围为±0.47 IU/ml（变异系数为13%），对于初始IFN-γ反应处于临界范围（0.25 - 0.80 IU/ml）的个体为±0.26 IU/ml（30%）。在非受控环境中变异性的估计范围显著更大（±1.4 IU/ml；60%）。注入QuantiFERON管中的血量和分析前延迟被确定为变异的关键来源。
这项系统评价表明，即使在相同条件下重复进行IFN-γ释放检测也存在显著变异性，这表明对现有切点附近的逆转和转换应谨慎解释。
