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-gamma 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-gamma 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-gamma).


RESULTS
We found all five new biomarkers were expressed in significantly higher concentrations compared to IFN-gamma. IP-10 and MCP-3 levels in the un-stimulated samples were higher in patients compared with controls.


CONCLUSIONS
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.
Ruhwald
Morten
M
Dep. of Infectious Diseases 144, Copenhagen University, Hvidovre Hospital, DK-2650 Hvidovre, Denmark. mruhwald@mail.dk
Bjerregaard-Andersen
Morten
M
Rabna
Paulo
P
Eugen-Olsen
Jesper
J
Ravn
Pernille
P