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 cutoff, 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)) 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)-gamma-induced protein (IP-10/CXCL10), monokine induced by IFN-gamma (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