@article {Uzorka2102665, author = {Jonathan W. Uzorka and Jaap A. Bakker and Krista E. van Meijgaarden and Eliane M.S. Leyten and Nathalie M. Delfos and David J. Hetem and Jos Kerremans and Mieke Zwarts and Sandra Cozijn and Tom H.M. Ottenhoff and Simone A. Joosten and Sandra M. Arend}, title = {Biomarkers to identify Mycobacterium tuberculosis infection among borderline QuantiFERON results}, volume = {60}, number = {2}, elocation-id = {2102665}, year = {2022}, doi = {10.1183/13993003.02665-2021}, publisher = {European Respiratory Society}, abstract = {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{\textperiodcentered}mL-1), low-negative (\<0.15 IU{\textperiodcentered}mL-1) or positive (>=0.35 IU{\textperiodcentered}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 patientsResults 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{\textendash}1.00) and specificity 0.95 (95\% CI 0.74{\textendash}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.Additional laboratory testing of IP-10/CXCL10 and MIG/CXCL9 in individuals at increased risk of reactivation TB with a borderline QuantiFERON-TB Gold Plus result just below the formal cut-off helps to identify those with M. tuberculosis infection https://bit.ly/3t8zR7r}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/60/2/2102665}, eprint = {https://erj.ersjournals.com/content/60/2/2102665.full.pdf}, journal = {European Respiratory Journal} }