Toward a rapid and accurate point-of-care test for active pulmonary tuberculosis: Multiplexed proteomic assay (SOMAscan™) of human serum for microbial and host markers

M.A. De Groote, L. Green, D. Sterling, R. Ostroff, N. Janjic, U. Ochsner
2014 International Journal of Infectious Diseases  
A rapid, accurate, and inexpensive tuberculosis (TB) diagnostic test would allow earlier treatment and reduce transmission. Methods & Materials: We used slow off-rate modified aptamers (SOMAmers) in a highly multiplexed proteomic assay (SOMAscan) to measure 1129 human proteins and 16 Mtb proteins in serum samples provided by the Foundation for Innovative New Diagnostics (FIND). Results: Among the top host serum biomarkers distinguishing TB from non-TB regardless of the HIV status were
more » ... n, TSP4, gelsolin, and CDON, which were lower in TB compared to non-TB, and LBP, ITI heavy chain H4, NPS-PLA2, and IP-10, which were higher in TB. A 9-marker model performed well in a training set of 173 TB vs. 160 non-TB samples (sens 89% / spec 88%, AUC = 0.94), which was confirmed in a blinded verification set of 132 TB vs. 118 non-TB (sens 80% / spec 84%, AUC = 0.88). Mtb pathogen-specific SOMAmers showed non-specific background in serum and are pending analytical optimization to improve performance. Additional work to improve sensitivity of the host markers is ongoing. Conclusion: The discovery of robust, quantitative, non-culture based diagnostic biomarkers of active pulmonary TB has great potential to facilitate the rapid and accurate diagnosis of TB disease. Our goal is that a combined host and microbial point-of-care diagnostic test could ultimately be tested and applied in peripheral microscopy centers or in primary care clinics. http://dx.
doi:10.1016/j.ijid.2014.03.1172 fatcat:mzqbzc3bnjbwzeeavhgsq4axjy