IP-10, MCP-1, MCP-2, MCP-3, and IL-1RA hold promise as biomarkers for infection with M. tuberculosis in a whole blood based T-cell assay

BACKGROUND: IFN-γ responses to M. tuberculosis antigens are used as in-vitro diagnostic tests for tuberculosis infection. The tests are highly specific but sensitivity may be impaired due to immuno-suppression. The objective of this small exploratory study was to compare three novel biomarkers for in-vitro diagnosis of tuberculosis – MCP-1, MCP-3 and IL-1RA – with the current established biomarker IFN-γ and the newly described IP-10 and MCP-2. METHODS: Whole blood from 8 patents with active tuberculosis and from 7 healthy controls was stimulated with M. tuberculosis specific antigens and mitogen in the Quantiferon In Tube test tubes. Levels of biomarkers were measured using Luminex and ELISA (IFN-γ). RESULTS: We found all five new biomarkers were expressed in significantly higher concentrations compared to IFN-γ. IP-10 and MCP-3 levels in the un-stimulated samples were higher in patients compared with controls. CONCLUSION: All biomarkers had diagnostic potential as they could differentiate between the patients and the controls. IP-10 and MCP-2 seemed most promising as they were expressed in high levels with antigen stimulation and were low in the un-stimulated samples. Further studies are needed to explore the potential of these highly expressed novel biomarkers individually and in combination.