Evaluation of QuantiFERON-TB Gold Plus on Liaison XL in a Low-Tuberculosis-Incidence Setting

Abstract

T he QuantiFERON-TB Gold Plus assay (QFT; Qiagen, Hilden, Germany) is a frequently used interferon gamma releasing assay (IGRA) for the diagnosis of latent tuberculosis infections (LTBI) (1, 2). Recently, it became available on Liaison XL (DiaSorin S.p.A., Saluggia, Italy), a fully automated analyzer using chemiluminescense detection within a chemiluminescent immunoassay (CLIA). In this study, we compared this novel method to the commonly used enzyme-linked immunosorbent assay (ELISA) in a low-incidence LTBI setting. Heparin blood samples (n ϭ 92) taken for routine QFT assays were analyzed with both assays on two different sites as follows: after incubation and centrifugation as instructed by the manufacturer, QFT CLIA was performed on-site (Ghent University Hospital, Belgium) on one aliquot of the processed plasma sample, while another aliquot was transported at room temperature to site two (University Hospital of Leuven, Belgium) for QFT ELISA on the BEP III platform (Siemens Healthcare Diagnostics, Eschborn, Germany). Results were interpreted according to the manufacturer's criteria (positivity threshold 0.35). Of the 92 samples, 46 were from males and 42 from females, median age of 45 years (range 1 to 91 years). Four samples were from encoded health care workers sent by the occupational medicine department. Eighty-seven samples (95%) returned concordant results: 12 positive, 71 negative, and 4 indeterminate results. Five samples (5%) were discordant (Table 1), of which four samples resulted in a major discrepancy, i.e., positive versus negative. Clinical information on these samples did not bring clarity and follow-up samples were not included within the scope of this comparison. However, the discordant samples were all lowpositive results which, when applying a suitable additional range, could be classified as borderline. The use of a borderline range remains subjective but is justified, particularly in a low LTBI setting and among patients with low individual risk for tuberculosis (3). The Belgian Lung and Tuberculosis Association (4) recently suggested defining borderline results as between 0.35 and 0.7, and recommended retesting of borderline samples. As this range has been defined based on QFT ELISAs, extrapolation to other systems might not be justifiable. In this study, CLIA returned significantly higher values for TB1/TB2 tubes than ELISA (Fig. 1). This quantitative difference is possibly due to preanalytics, where QFT CLIA was performed on-site while QFT ELISA required transport to site two, causing a delay of at least one day and leading to possible degradation of interferon gamma. However, in 2 of 5 discordant samples, higher levels (positive results) were measured in the QFT ELISA, suggesting this explanation might fall short. Another possibility is that the difference is intrinsic to the detection method.

QuantiFERON-TB Gold Plus with Chemiluminescence Immunoassay: Do We Need a Higher Cutoff?

“…Linear regression analysis indicated substantial correlation between ELISA and CLIA despite the two different methods of measurement; however, CLIA produced significantly higher values both for TB1 and TB2 than ELISA. This is in agreement with previous data on CLIA performance in a smaller study population (11). In our opinion, this difference is not due to preanalytical factors but rather to the intrinsic chemistry of the assay based on chemiluminescence technology with paramagnetic microparticle solid phase, allowing the detection of very low levels of IFN-␥ (13,19).…”

“…CLIA repeatability and reproducibility on this platform were studied by Brantestig et al, who found that the imprecision of the method is within an acceptable range and analysis of linearity showed acceptable recovery (12). Furthermore, a recent study by De Maertelaere et al conducted on 92 samples showed that CLIA gave significantly higher values for TB1 and TB2 than ELISA (11).…”

“…Recently, new chemiluminescence immunoassays (CLIA) have been developed to detect IFN-␥ in human plasma samples. However, to date, only a few studies have been published comparing QFT-Plus and the previous version QFT-TB Gold In-Tube by ELISA to CLIA (11)(12)(13). Among these, the study with the most relevant sample size (341 samples) reports a high degree of agreement (99.1%) between the two methods, using the AdvanSure I3 platform for CLIA (13).…”

Differential Diagnosis of Latent Tuberculosis Infection and Active Tuberculosis: A Key to a Successful Tuberculosis Control Strategy

“…To overcome the deficiencies of the TST, IGRAs have been developed as an alternative immunodiagnostic approach. Thus far, there are five commercialized IGRA kits, including the T-cell spot of the TB assay (T-SPOT.TB, Oxford Immunotec, Abingdon, UK), QuantiFERON-TB Gold In-Tube (QFT-GIT, Qiagen GmbH, Hilden, Germany), QuantiFERON-TB Gold-Plus (QFT-Plus, Qiagen, MD, United States), LIAISON QuantiFERON-TB Gold Plus (LIAISON QFT-Plus, DiaSorin S.p.A., Italy), and LIOFeron TB/LTBI (LIONEX GmbH, Braunschweig, Germany) (De Maertelaere et al, 2020;Della Bella et al, 2020;Altawallbeh et al, 2021;Hamada et al, 2021). In addition, there are five products in development-T-Track (R) TB (Lophius Biosciences GmbH), VIDAS TB-IGRA (bioMérieux), Access QuantiFERON-TB (Boditech Med Inc.), ichroma TM IGRATB (Boditech Med Inc.), and IP-10 IGRA elisa/lateral flow (rBioPharm) (WHO, 2020).…”

QuantiFERON-TB Gold Plus and QuantiFERON-TB Gold In-tube assays for detecting latent tuberculosis infection in Thai healthcare workers

“…However, the QFT-Plus performance within endemic settings has been documented less. Nonetheless, comparative data on the performance of QFT-GIT and QFT-Plus in LTBI detection are largely based on middle or low TB-incidence settings 7 , 16 – 18 . Therefore, we aim to compare the two tests in Thailand, where the TB burden is high.…”