title: Identification of novel host biomarkers in plasma as candidates for the immunodiagnosis of tuberculosis disease and monitoring of tuberculosis treatment response.
abstract: 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.
authors.affiliation: 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.
authors.forename: Ruschca
authors.initials: R
authors.lastname: Jacobs
authors.affiliation: 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.
authors.forename: Stephanus
authors.initials: S
authors.lastname: Malherbe
authors.affiliation: 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.
authors.forename: Andre G
authors.initials: AG
authors.lastname: Loxton
authors.affiliation: 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.
authors.forename: Kim
authors.initials: K
authors.lastname: Stanley
authors.affiliation: 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.
authors.forename: Gian
authors.initials: G
authors.lastname: van der Spuy
authors.affiliation: 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.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
authors.affiliation: 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.
authors.forename: Novel N
authors.initials: NN
authors.lastname: Chegou
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000150:complications; D006801:Humans; D007159:Immunologic Tests / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019095:Point-of-Care Systems; D012372:ROC Curve; D015203:Reproducibility of Results; D013019:South Africa; D014376:Tuberculosis / Q000175:diagnosis / Q000628:therapy*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000628:therapy*
chemical_list: D015415:Biomarkers; D007371:Interferon-gamma
keywords: Immune response; Immunity; Immunology and Microbiology Section; acute phase proteins; biomarker; diagnosis; neural cell adhesion molecule (NCAM); tuberculosis