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

Abstract

The 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 (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=92) taken for routine QFT assay were analyzed with both assays on two different sites: after incubation and centrifugation as instructed by the manufacturer, on one aliquot of the processed plasma sample QFT CLIA was performed on-site (Ghent University Hospital, Belgium) 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 1-91 years). Four samples were from encoded healthcare workers sent by the occupational medicine department.Eighty-seven samples (95%) returned concordant results: 12 positive, 71 negative and four 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, it were all low positive 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 to define borderline results between 0.35-0.7, and recommends to re-test borderline samples. As this range has been defined based on QFT ELISA tests, extrapolation to other systems might not be justifiable.In this study, CLIA returned significantly higher values for TB1/TB2 than ELISA (Figure 1). This quantitative difference is possibly due to pre-analytics: QFT CLIA was performed on-site, while for QFT ELISA transport to site two caused a delay of minimum one day with possible degradation of interferon-gamma. However, in 2/5 discordant samples higher levels (positive results) were measured in QFT ELISA suggesting this explanation might fall short. Another possibility is that the difference is intrinsic to the detection method.Considering that CLIA testing may give higher values, an adapted borderline threshold may need to be defined for QFT CLIA. This needs to be re-evaluated on a bigger prospective cohort with inclusion of the clinical data and follow-up samples.In conclusion, the QFT CLIA on LIAISON® XL shows comparable performance to the detection with QFT ELISA in a low LTBI incidence setting. There is a need to define a borderline range, which possibly needs to be adjusted according to the incidence setting and the detection method, and should be based on clinical diagnostics criteria.