Research Papers: Immunology:

Identification of novel host biomarkers in plasma as candidates for the immunodiagnosis of tuberculosis disease and monitoring of tuberculosis treatment response

Ruschca Jacobs, Stephanus Malherbe, Andre G. Loxton, Kim Stanley, Gian van der Spuy, Gerhard Walzl and Novel N. Chegou _

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Oncotarget. 2016; 7:57581-57592. https://doi.org/10.18632/oncotarget.11420

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Ruschca Jacobs1, Stephanus Malherbe1, Andre G. Loxton1, Kim Stanley1, Gian van der Spuy1, Gerhard Walzl1 and Novel N. Chegou1

1 Department of Biomedical Sciences, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research and SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

Correspondence to:

Novel N. Chegou, email:

Keywords: tuberculosis, diagnosis, biomarker, neural cell adhesion molecule (NCAM), acute phase proteins, Immunology and Microbiology Section, Immune response, Immunity

Received: April 15, 2016 Accepted: August 13, 2016 Published: August 19, 2016


There is an urgent need for new tools for the rapid diagnosis of tuberculosis disease. We evaluated the potentials of 74 host markers as biomarkers for the immunological diagnosis of tuberculosis and monitoring of treatment response. Fifty-five individuals that presented with signs and symptoms requiring investigation for tuberculosis disease were prospectively recruited prior to clinical diagnosis, at a health centre in Cape Town, South Africa. Patients were later classified as having tuberculosis disease or other respiratory diseases (ORD) using a combination of clinical, radiological and laboratory findings. Out of 74 host markers that were evaluated in plasma samples from study participants using a multiplex platform, 18 showed potential as tuberculosis diagnostic candidates with the most promising being NCAM, CRP, SAP, IP-10, ferritin, TPA, I-309, and MIG, which diagnosed tuberculosis disease individually, with area under the ROC curve ≥0.80. Six-marker biosignatures containing NCAM diagnosed tuberculosis disease with a sensitivity of 100% (95%CI, 86.3-100%) and specificity of 89.3% (95%CI, 67.6-97.3%) irrespective of HIV status, and 100% accuracy in the absence of HIV infection. Furthermore, the concentrations of 11 of these proteins changed with treatment, thereby indicating that they may be useful in monitoring of the response to tuberculosis treatment. Our findings have potential to be translated into a point-of-care screening test for tuberculosis, after future validation studies.

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