Quantitative analysis of interferon-γ release assay response in children with latent and active tuberculosis

The use of interferon-γ (IFN-γ) release assays (IGRAs) for the diagnosis of tuberculosis (TB) infection in children is still under debate because of concerns about their immature immune response.The aim of this study was to investigate quantitative values of QuantiFERON®-TB Gold In-Tube (QFT-IT), a commercially available IGRA, in a large cohort of children screened for TB infection.A retrospective analysis was conducted on samples from 517 children aged 0-14 years old at the Pediatric Unit of S. Orsola-Malpighi University Hospital of Bologna (Italy); quantitative responses to QFT-IT stimuli were analyzed according to diagnosis and age.Elevated IFN-γ values in the QFT-IT Nil (background) tube were statistically associated to diagnosis of active TB. Quantitative IFN-γ response to MTB specific antigens (TB Ag) was not significantly different between children with active and latent TB infection (LTBI), even though the median values were higher in the first group. When children were grouped by age, those less than 5 years old produced significantly higher levels of IFN-γ in response to TB Ag if they had active TB (median 10 IU/ml) than those with LTBI (median 1.96 IU/ml). IFN-γ response to Mitogen increased with age. The overall rate of indeterminate results was low (3.9%) and no indeterminate QFT-IT were observed in active or latent TB patients.In conclusion, quantitative QFT-IT values could provide further information to clinicians to manage TB in children, and these observations could be transferred to the new version of the test, QuantiFERON®-TB Gold Plus, which to date lacks data from the pediatric population.