Fourth-generation chemiluminescence QuantiFERON-TB Plus assay (CLIA) <i>versus</i> T-SPOT.TB semiautomated 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-gamma 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 3,748 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-CLIA; 9.9% T-SPOT.TB). Indeterminate results were infrequent (1.8% QFT-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 y: 15.4%), older adults (≥75 y: 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-CLIA-positive/T-SPOT.TB-negative patterns (131/181; 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 interpretetative value when contextualized by disease group and assay specific behaviour IGRA.