Identification of novel tuberculosis diagnostic biomarkers in plasma and saliva

Abstract

There is an urgent need for new tools for the rapid diagnosis of tuberculosis (TB) disease, and monitoring of the response to TB treatment, especially in resource-poor settings. Immunodiagnostic approaches might be beneficial, especially if based on the detection of host biomarkers in easily available samples such as serum, plasma or saliva, as they may be easily adaptable into point-of-care tests. The aim of the current study was to identify such candidate biomarkers. We recruited 22 TB patients and 33 individuals with suspected TB, but in whom TB disease was ruled out, at a health centre in Cape Town, South Africa. Using a multiplex platform, we evaluated the levels of 74 host markers in plasma and saliva samples from these individuals, as candidates for the diagnosis of TB disease or monitoring of TB treatment response. The concentrations of 23 host markers detected in plasma and 5 detected in saliva diagnosed TB disease AUC ≥ 0.80. However, the optimal diagnostic biosignature was a combination of neural cell adhesion molecule (NCAM),IL-17A, thrombopoietin(TPO),complement C4 and transthyretin, which diagnosed TB disease with a sensitivity of 100% and specificity of 86% after leave-one-out cross validation. When compared to baseline levels, multiple host markers detected in plasma and saliva were significantly different between diagnosis and end of TB treatment, thereby indicating that they may be potentially useful in monitoring of TB treatment response. In conclusion, we have identified candidate host biomarkers in plasma and saliva samples, which may be useful in the diagnosis of TB disease and monitoring of the response to TB treatment. Our findings require further validation in larger studies.