Cytokine responses to QuantiFERON® peptides, purified protein derivative and recombinant ESAT-6 in children with tuberculosis.

Abstract

SETTING: Recent data suggest that interferon-gamma release assays may have reduced sensitivity in children. OBJECTIVE: To explore the cellular responses in children infected with tuberculosis (TB) to different mycobacterial antigens, including the peptides used in the QuantiFERON®-TB Gold In-Tube (QFT) assay. DESIGN: Cytokines were measured by multiplex analyte detection in supernatants after stimulation with peptides in QFT, purified protein derivative (PPD) and recombinant whole protein ESAT-6. Samples from 11 children with active TB, 46 healthy children with latent tuberculosis infection (LTBI), and 35 healthy non-infected children were analyzed. RESULTS: None of the cytokines examined in the QFT peptide stimulation assay distinguished between non-infected children and those aged <5 years with LTBI. Cytokines interleukin-2 and transforming growth factor-beta 1 (TGF-β1) were shown to distinguish between stages of Mycobacterium tuberculosis infection after blood was stimulated with the QFT peptides. All children had significantly higher Th 1 and 2 cytokine production against PPD than against the other antigens tested. CONCLUSION: Measuring specific cytokine patterns after stimulation with the QFT peptides may not increase sensitivity in diagnosing LTBI in children, but there may be future diagnostic value in determining the stage of infection. PPD-stimulated blood produced a robust and diverse cytokine response in young children, making it an interesting antigen for in vitro diagnostic studies.