Abstract

BackgroundThe blood based interferon-gamma release assays (IGRA) for the diagnosis of tuberculosis do not discriminate between active TB disease and latent TB infection (LTBI). The search for distinguishing biomarkers therefore continues, as the accurate diagnosis of tuberculosis is particularly challenging in children. IFN-γ-inducible protein 10 (IP-10/CXCL10) has recently been evaluated as a marker for active TB in adults with promising results.AimTo investigate this new biomarker for active TB and LTBI in paediatrics.MethodWe measured IP-10 levels using ELISA in supernatants of whole blood samples stimulated with TB-specific-antigens and negative control antigen.ResultsIP-10 is produced in high levels following mycobacterial antigen stimulation in active TB (n = 17) and LTBI (n = 16) compared to controls (n = 16) and to IFN-γ. The baseline levels of IP-10 are increased in active TB and in LTBI, but there is no significant difference of stimulated levels of IP-10 between active TB and LTBI.ConclusionsIP-10 is a biomarker for tuberculosis in children. However like IFNγ, IP-10 also does not distinguish between active TB and LTBI.

Highlights

  • The diagnosis of tuberculosis (TB) in the paediatric population remains a challenge, as TB can present to many common childhood infections and shares many symptoms with HIV

  • The baseline levels of inducible protein 10 (IP-10) are increased in active TB and in latent TB infection (LTBI), but there is no significant difference of stimulated levels of IP-10 between active TB and LTBI

  • IP-10 is a biomarker for tuberculosis in children

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Summary

Introduction

The diagnosis of tuberculosis (TB) in the paediatric population remains a challenge, as TB can present to many common childhood infections and shares many symptoms with HIV. In recent years new immunodiagnostic tests for tuberculosis have been developed: the commercially available Quantiferon TB Gold In Tube (Cellestis, Carnegie, Australia) and T-SPOT TB (Oxford Immunotec, Abingdon, UK) ELISPOT assays both measure interferon gamma (IFN-c) release by sensitized T cells after stimulation with peptides of M. tuberculosis specific antigens - Early Secretory Antigenic Target (ESAT)-6, Culture Filtrate Protein (CFP)-10 plus TB7.7 in the Quantiferon system.[3] These interferon gamma release assays (IGRA) are less influenced than the TST by factors frequently associated with childhood tuberculosis in developing countries, such as malnutrition and HIV co-infection [4]. The IGRA poorly distinguish between active TB and latent TB infection (LTBI) and more recent studies question the sensitivity of these assays, in some groups including younger children and immunocompromised patients. IFN-c-inducible protein 10 (IP-10/CXCL10) has recently been evaluated as a marker for active TB in adults with promising results

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