Diagnostic accuracy of IP-10 mRNA release assay for tuberculosis

Interferon-gamma (IFN-γ) release assays (IGRAs) are increasingly used to test for latent TB infection. Although highly specific, IGRAs have a relatively high false-negative rate in active TB patients. A more sensitive assay is needed. IP-10 is an alternative biomarker with a 100 fold high expression level compared to IFN-γ, allowing for different analysis platforms including molecular detection. The PCR technique is already an integrated tool in most TB laboratories and thus an obvious platform to turn to. In this case-control study, we investigated the diagnostic sensitivity and specificity of a molecular assay detecting IP-10 mRNA expression following antigen stimulation of a blood sample. We included 89 TB patients and 99 healthy controls. Blood was drawn in QuantiFERON-TB Gold In-Tube (QFT) tubes. Eight hours post-stimulation IP-10 mRNA expression was analyzed and 20 hours post-stimulation IP-10 and IFN-γ protein plasma levels were analyzed using an in-house IP-10 ELISA and the official QFT ELISA, respectively. The IP-10 mRNA assay provided a high specificity (98%) and sensitivity (80%) and AUC=0.97, however, the QFT assay provided a higher overall diagnostic potential with specificity (100%) and sensitivity (90%) and AUC=0.99. The IP-10 protein assay performed on par with the QFT assay with specificity (98%) and sensitivity (87%) and AUC=0.98. We have provided proof of high technical performance of a molecular assay detecting IP-10 mRNA expression. As a diagnostic tool, this assay would gain from further optimization especially on the kinetics of IP-10 mRNA expression.