TY - JOUR
T1 - A multiplexed and miniaturized serological tuberculosis assay identifies antigens that discriminate maximally between TB and non-TB sera
AU - Tong, Miao
AU - Jacobi, Catharina E.
AU - Van De Rijke, Frans M.
AU - Kuijper, Sjoukje
AU - Van De Werken, Sjaak
AU - Lowary, Todd L.
AU - Hokke, Cornelis H.
AU - Appelmelk, Ben J.
AU - Nagelkerke, Nico J.D.
AU - Tanke, Hans J.
AU - Van Gijlswijk, Rob P.M.
AU - Veuskens, Jacques
AU - Kolk, Arend H.J.
AU - Raap, Anton K.
N1 - Funding Information:
This work was supported by the European Commission of the European Union program FP5 CRAFT project QLK2-CT-202-70963.
Funding Information:
SW was supported by the Scientific Research for the Tropics (WOTRO) fund of Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO). NIH, NIAID contract N01 AI-75320 and Colorado State University made the lipopolysaccharide fractions available for this study. We wish to acknowledge Dr. Chris Alberts for providing the sera from sarcoidosis patients. [MT]
PY - 2005/6
Y1 - 2005/6
N2 - We have developed a multiplexed and miniaturized TB serological assay with the aim of identifying (combinations of) antigens that maximally discriminate between TB and non-TB patients. It features a microarray accommodating 54 TB antigens, less than 1 μl serum consumption and an indirect immunofluorescence detection protocol. With a panel of 20 TB and 80 non-TB sera we ranked combinations of TB antigens with respect to sensitivity and specificity of TB detection by means of logistic step-forward regression analysis. The highest-ranking TB antigen combination had an area-under-the-curve of the receiver-operator-characteristics (ROC) of 0.95. We also identified an antigen that on its own provided good specificity and sensitivity of TB detection (Ara6-BSA; area-under-the-ROC curve: 0.90). These area-under-the-ROC curve values are exceptionally high for a serological TB assay. We conclude that TB antigen microarrays permit rapid identification of TB antigens that, either alone or in combination, discriminate maximally between TB and non-TB patients and that such identification provides an excellent starting point for developing point-of-care diagnostic assays.
AB - We have developed a multiplexed and miniaturized TB serological assay with the aim of identifying (combinations of) antigens that maximally discriminate between TB and non-TB patients. It features a microarray accommodating 54 TB antigens, less than 1 μl serum consumption and an indirect immunofluorescence detection protocol. With a panel of 20 TB and 80 non-TB sera we ranked combinations of TB antigens with respect to sensitivity and specificity of TB detection by means of logistic step-forward regression analysis. The highest-ranking TB antigen combination had an area-under-the-curve of the receiver-operator-characteristics (ROC) of 0.95. We also identified an antigen that on its own provided good specificity and sensitivity of TB detection (Ara6-BSA; area-under-the-ROC curve: 0.90). These area-under-the-ROC curve values are exceptionally high for a serological TB assay. We conclude that TB antigen microarrays permit rapid identification of TB antigens that, either alone or in combination, discriminate maximally between TB and non-TB patients and that such identification provides an excellent starting point for developing point-of-care diagnostic assays.
KW - Microarray
KW - Multi-variant analysis
KW - Multiplexing
KW - ROC analysis
KW - Serology
KW - Tuberculosis
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U2 - 10.1016/j.jim.2005.04.004
DO - 10.1016/j.jim.2005.04.004
M3 - Article
C2 - 15979638
AN - SCOPUS:21844451364
SN - 0022-1759
VL - 301
SP - 154
EP - 163
JO - Journal of Immunological Methods
JF - Journal of Immunological Methods
IS - 1-2
ER -