LAUSR

Objectives: New tests are urgently needed for the diagnosis of TB disease. Serodiagnostic tests may be useful, as they may be easily adaptable into point-of-care tests. The aim of the current study was to evaluate the usefulness of antibody responses against novel M tuberculosis (Mtb) antigens as tools for the diagnosis of TB disease. Methods: We prospectively collected plasma samples from individuals presenting with symptoms suggestive of TB disease at a primary health care clinic in Cape Town, South Africa. Patients were later classified as having TB or other respiratory diseases. We evaluated IgA and IgM antibody responses against seven Mtb antigens in plasma samples and assessed their diagnostic potentials by receiver operator characteristic (ROC) curve analysis. We also assessed the utility of biosignatures comprising antibodies and cytokines in the diagnosis of TB disease. Results: Out of the 156 study participants, 28 (18%) were HIV infected and 26 were diagnosed with TB disease. IgA and IgM responses against single antigens, including NarL, Rv3019c, and two other proteins, showed potential in the diagnosis of TB disease, with area under the ROC curve (AUC) up to 0.74. A seven-antibody biosignature diagnosed TB disease with an AUC of 0.8, whereas a combination of two antibodies and five host biomarkers diagnosed TB disease with a sensitivity of 95% (CI, 73%-100%) and specificity of 89% (CI, 68.7%-97%). Conclusion: Although antibodies showed potential in the diagnosis of TB disease, the use of host inflammatory biomarkers in combination with antibodies may result in more accurate diagnostic tools for TB disease.