Borderline QuantiFERON results and the distinction between specific responses and test variability. (July 2018)

• Record Type: Journal Article
• Authors: Uzorka, Jonathan W.; Bossink, Ailko W.J.; Franken, Willeke P.J.; Thijsen, Steven F.T.; Leyten, Eliane M.S.; van Haeften, Alida C.; Doornenbal, Gert; Boonstra, Peter; Ottenhoff, Tom H.M.; Arend, Sandra M.
• Is Part Of: Tuberculosis. Volume 111(2018)
• Page Start: 102
• Page End: 108
• Publication Date: 2018-07
• Subjects: Elispot -- Interferon-gamma release tests -- Cut-off -- QuantiFERON -- Tuberculosis; 616.995
• DOI: 10.1016/j.tube.2018.06.002
• Languages: English
• ISSNs: 1472-9792

Abstract

Abstract: Background: QuantiFERON (QFT) results near the cut-off are subject to debate. We aimed to investigate which borderline QFT results were due to Mycobacterium tuberculosis ( Mtb )-specific responses or to test variability. Methods: In a contact investigation, tuberculin skin test (TST), QFT and T-SPOT. TB (T-SPOT) were performed in 785 BCG-unvaccinated contacts. Contacts with a low-negative (<0.15), borderline (0.15–0.35), low-positive (0.35–0.70) or high-positive QFT (≥0.70 IU/mL) were compared with respect to exposure, TST and T-SPOT results. Development of active tuberculosis was assessed. Results: Borderline QFT results occurred in threefold excess over test variability (p = 0.0027). In contacts with low-negative, borderline or positive QFT results, a positive TST occurred in 24.9%, 62.1% and 91.4% (p < 0.0001) and a positive T-SPOT result in 6.3%, 41.3% and 86.4%, respectively (p < 0.0001). Two-third (20/29) of contacts with a borderline and 14/16 (88%) with a low-positive QFT had a positive TST and/or T-SPOT, indicating probable Mtb -infection. During 12 years of follow-up, seven patients were diagnosed with active tuberculosis, two of whom after a low-positive QFT. Conclusions: In this study, most borderline and low-positive QFT results were Mtb -specific, showing the biological significance of a borderline QFT. The clinical relevance, however, will be most distinct in patients who are or will be immunocompromised.