Fourth-generation chemiluminescence QuantiFERON-TB Plus assay versus T-SPOT.TB semi-automated assay: a case for the use of both assays in immunosuppressed patients.

BACKGROUND

The World Health Organization recommends screening and providing preventive treatment of tuberculosis in high-risk groups. We compared the performance of the latest versions of two widely used interferon (IFN)-γ release assays (IGRAs), the QuantiFERON-TB Gold Plus chemiluminescent assay (QFT-Plus CLIA) and the semi-automated T-SPOT.TB assay, and assessed the potential benefit of a dual-testing strategy in immunosuppressed patients and/or candidates for biological therapy.

METHODS

From September 2022 to December 2023, we included 3748 immunosuppressed patients. IGRAs were performed according to manufacturers' instructions. Agreement was evaluated using Cohen's kappa (κ), and subgroup analyses were stratified by age and underlying disease.

RESULTS

At least one IGRA was positive in 13.4% of patients (12.0% QFT-Plus CLIA; 9.9% T-SPOT.TB). Indeterminate results were infrequent (1.8% QFT-Plus CLIA; 2.6% T-SPOT.TB). Overall agreement was high (93.0%; κ=0.67), but lower among IGRA-positive cases (63.9%; κ=0.62). Discrepancies occurred in 7.0% of patients, most frequently in children (0-14 years: 15.4%), older adults (≥75 years: 13.8%), individuals living with HIV (38%), rheumatoid arthritis/Sjögren's syndrome (12.4%) and other chronic inflammatory diseases, transplant recipients or immunodeficiencies (11.9%). Among IGRA-positive cases (n=502), most discordant results corresponded to QFT-Plus CLIA-positive/T-SPOT.TB-negative patterns (131 of 181; 72.4%).

CONCLUSION

In immunosuppressed patients, dual IGRA testing enhances diagnostic sensitivity and can strengthen clinical decision-making. Concordant results increase diagnostic certainty, whereas discordant findings gain interpretative value when contextualised by disease group and assay-specific behaviour IGRA.