Plasma host protein signatures correlating with Mycobacterium tuberculosis activity prior to and during antituberculosis treatment

Abstract

There is a need for rapid non-sputum-based tests to identify and treat patients infected with Mycobacterium tuberculosis (Mtb). The overall objective of this study was to measure and compare the expression of a selected panel of human plasma proteins in patients with active pulmonary tuberculosis (ATB) throughout anti-TB treatment (from baseline to the end of treatment), in Mtb-infected individuals (TBI) and healthy donors (HD) to identify a putative host-protein signature useful for both TB diagnosis and treatment monitoring. A panel of seven human host proteins CLEC3B, SELL, IGFBP3, IP10, CD14, ECM1 and C1Q were measured in the plasma isolated from an HIV-negative prospective cohort of 37 ATB, 24 TBI and 23 HD. The protein signatures were assessed using a Luminex xMAP® to quantify the plasmatic levels in unstimulated blood of the different clinical group as well as the protein levels at baseline and at three timepoints during the 6-months ATB treatment, to compare the plasma protein levels between culture slow and fast converters that may contribute to monitor the TB treatment outcome. Protein signatures were defined using the CombiROC algorithm and multivariate models. The studied plasma host proteins showed different levels between the clinical groups and during the TB treatment. Six of the plasma proteins (CLEC3B, SELL, IGFBP3, IP10, CD14 and C1Q) showed significant differences in normalised median fluorescence intensities when comparing ATB vs HD or TBI groups while ECM1 revealed a significant difference between fast and slow sputum culture converters after 2 months following treatment (p = 0.006). The expression of a four-host protein markers (CLEC3B-ECM1-IP10-SELL) was significantly different between ATB from HD or TBI groups (respectively, p < 0.05). The expression of the same signature was significantly different between the slow vs the fast sputum culture converters after 2 months of treatment (p < 0.05). The results suggest a promising 4 host-plasma marker signature that would be associated with both TB diagnostic and treatment monitoring.