Interferon-gamma inducible protein 10 as a biomarker for active tuberculosis and latent tuberculosis infection in children: A case–control study

Abstract

Background: Interferon-gamma (IFN-γ) release assays (IGRAs) are suboptimally sensitive to diagnose tuberculosis (TB) and latent TB infection (LTBI) in young children. In this study we compared Mycobacterium tuberculosis antigen-stimulated IFN-γ inducible protein 10 (IP-10) responses in children with active TB and LTBI to responses from children with non-tuberculous mycobacterial (NTM) lymphadenopathy and respiratory tract infection (RTI). We also assessed test agreement between IP-10 and the QuantiFERON^®-TB Gold In-Tube (QFT-IT) test results, and investigated whether IP-10 release upon mitogen stimulation is associated with age. Methods: We recruited 48 children (median age 54 months) diagnosed in Germany with either active TB (n = 11), LTBI (n = 14), NTM lymphadenopathy (n = 8), or common RTI (n = 15). IFN-γ levels were measured using the QFT-IT. These plasma supernatants were used to determine IP-10 concentrations using an in-house enzyme-linked immunosorbent assay (ELISA). Results: The median antigen-stimulated IP-10 levels in children with active TB, LTBI, NTM lymphadenopathy, and RTI were 12,702 pg/ml, 9109 pg/ml, 97 pg/ml, and 84 pg/ml, respectively. We observed a strong correlation between IP-10 and IFN-γ plasma concentration in children with active TB and LTBI (r² = 0.69). Overall agreement between IP-10 and QFT-IT assays was high (kappa = 0.95). IP-10 levels after mitogen stimulation showed no association with age. Conclusions: IP-10 and IFN-γ were both induced with antigen stimulation in blood from children in the TB and LTBI groups, in contrast to the NTM and RTI groups. Compared to IFN-γ the IP-10 levels were higher and IP-10 was released independently of age. IP-10 therefore may represent an additional biomarker in the paediatric population.

Keywords::

• IP-10
• interferon-gamma
• tuberculosis
• LTBI
• child

Acknowledgements

The authors are grateful to the laboratory staff of HELIOS Klinikum Emil von Behring and Hvidovre Hospital and to all the physicians and patients who took part in this study for their support.

Declaration of interest: Morten Ruhwald is registered as inventor on issued and pending patents owned by Hvidovre Hospital disclosing IP-10 as a marker for Mycobacterium tuberculosis infection and disease. Holger Rüssmann has received research funding from Ludwig-Maximilians University, Munich.