RD-1 antigen based in vitro diagnosis of TB infection: IP-10/CXCL10 is a novel potent biomarker with comparable performance to the Quantiferon In Tube test
Abstract number: O306
Ruhwald M., Bodmer T., Maier C., Andersen M., Eugen-Olsen J., Ravn P.
Objectives: A major breakthrough in clinical management of tuberculosis infection has been the development of in vitro diagnostic tests measuring IFN-g in response to stimulation with RD-1 antigens (IGRA tests). The tests perform with excellent specificity, but there is a concern that the sensitivity is not optimal, especially in patients with immune-suppression and in children. We have identified the chemokine IP-10/CXCL10 as a novel potential diagnostic biomarker for TB. The aim of the study was to establish a diagnostic test algorithm based on IP-10, and compare it with the QFT-IT results.
Materials and Methods: We measured IP-10 levels in plasma supernatants from Quantiferon In Tube (QFT-IT) stimulated whole blood from 80 patients with culture and/or PCR proven active TB, 86 unexposed Danish high school students, and 38 unexposed high school teachers. Based on ROC curve analysis we established two IP-10 cut-off points and constructed a diagnostic test algorithm inspired by the QFT-IT test; with positive, negative, and indeterminate test outcome.
Results: TB patients produced significantly higher levels of IP-10 and IFN-g compared with controls: for IFN-g median 215 pg/ml (IQR 22651 pg/ml) vs. 0 pg/ml (IQR 00 pg/ml), for IP-10 median 2158 pg/ml (IQR 5825882 pg/ml) vs. 37 pg/ml (IQR 1399 pg/ml. IP-10 and IFN-g responses were highly correlated (0.81, p < 0.0001). Based on ROC curve analysis we selected a sensitive IP-10 cut-off (237 pg/ml), and a specific cut-off (673 pg/ml). A cut off for indeterminate test was established by comparing the mitogen IP-10/IFN-g ratio. QFT-IT and the specific IP-10 test showed comparable performance with equal sensitivity/specificity and 90% agreement (kappa 0.79), table 1. The sensitive IP-10 test had a higher sensitivity 71/80 (90%), but also a high degree of positive responders among the controls 14/124 (11%), primarily among the older teachers (10/14)
Discussion: IP-10 is expressed in response to the RD1 antigens in consistent and significant higher levels than IFN-g. IP-10 has properties that enable the development of diagnostic test algorithm with positive, negative and indeterminate outcomes, performing with excellent concordance and comparable or even superior discriminatory power compared with the QFT-IT. As IP-10 is expressed in high amounts, it holds promise for the development of a new generation of more sensitive TB tests with simpler and potentially field-friendly read out formats, such as the lateral flow dipstick.
Table 1. Concordance between Quantiferon in Tube test (QFT-IT) and the Specific IP-10 test.
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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