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Biomarkers to identify Mycobacterium tuberculosis infection among borderline QuantiFERON results
Background Screening for tuberculosis (TB) infection often includes QuantiFERON-TB Gold Plus (QFT) testing. Previous studies showed that two-thirds of patients with negative QFT results just below the cut-off, so-called borderline test results, nevertheless had other evidence of TB infection. This study aimed to identify a biomarker profile by which borderline QFT results due to TB infection can be distinguished from random test variation.
Methods QFT supernatants of patients with a borderline (≥0.15 and <0.35 IU·mL−1), low-negative (<0.15 IU·mL−1) or positive (≥0.35 IU·mL−1) QFT result were collected in three hospitals. Bead-based multiplex assays were used to analyse 48 different cytokines, chemokines and growth factors. A prediction model was derived using LASSO regression and applied further to discriminate QFT-positive Mycobacterium tuberculosis-infected patients from borderline...
Show moreBackground Screening for tuberculosis (TB) infection often includes QuantiFERON-TB Gold Plus (QFT) testing. Previous studies showed that two-thirds of patients with negative QFT results just below the cut-off, so-called borderline test results, nevertheless had other evidence of TB infection. This study aimed to identify a biomarker profile by which borderline QFT results due to TB infection can be distinguished from random test variation.
Methods QFT supernatants of patients with a borderline (≥0.15 and <0.35 IU·mL−1), low-negative (<0.15 IU·mL−1) or positive (≥0.35 IU·mL−1) QFT result were collected in three hospitals. Bead-based multiplex assays were used to analyse 48 different cytokines, chemokines and growth factors. A prediction model was derived using LASSO regression and applied further to discriminate QFT-positive Mycobacterium tuberculosis-infected patients from borderline QFT patients and QFT-negative patients
Results QFT samples of 195 patients were collected and analysed. Global testing revealed that the levels of 10 kDa interferon (IFN)-γ-induced protein (IP-10/CXCL10), monokine induced by IFN-γ (MIG/CXCL9) and interleukin-1 receptor antagonist in the antigen-stimulated tubes were each significantly higher in patients with a positive QFT result compared with low-negative QFT individuals (p<0.001). A prediction model based on IP-10 and MIG proved highly accurate in discriminating patients with a positive QFT (TB infection) from uninfected individuals with a low-negative QFT (sensitivity 1.00 (95% CI 0.79–1.00) and specificity 0.95 (95% CI 0.74–1.00)). This same model predicted TB infection in 68% of 87 patients with a borderline QFT result.
Conclusions This study was able to classify borderline QFT results as likely infection-related or random. These findings support additional laboratory testing for either IP-10 or MIG following a borderline QFT result for individuals at increased risk of reactivation TB.
Show less- All authors
- Uzorka, J.W.; Bakker, J.A.; Meijgaarden, K.E. van; Leyten, E.M.S.; Delfos, N.M.; Hetem, D.J.; Kerremans, J.; Zwarts, M.; Cozijn, S.; Ottenhoff, T.H.M.; Joosten, S.A.; Arend, S.M.
- Date
- 2022-08-01
- Journal
- European Respiratory Journal
- Volume
- 60
- Issue
- 2