Abstract
There is an urgent need to rapidly diagnose tuberculosis (TB) disease and effectively monitor anti-TB treatment responses. Host-directed therapy (HDT) is a promising platform to mitigate challenges in TB diagnosis and anti-TB treatment response monitoring. Identifying changes in systemic proteins and immune cell distributions during the disease is an integral aspect of developing targeted therapies. Here, samples were collected from healthy individuals (CTRL) [n = 32 plasma, n = 9 bronchoalveolar lavage (BAL)] and newly diagnosed TB patients (TB treatment group) [n = 82 plasma, n = 28 BAL] to analyze full blood count, secreted levels of full-length osteopontin (OPN), and inflammatory markers. Peripheral blood and BAL samples were collected at a single time-point from CTRL, while in TB participants, they were collected at TB diagnosis (TBDx), week 1 (TBW1), month 2 (TBM2), and month 6 (TBM6). We observed a significantly increased monocyte-to-lymphocyte ratio (MLR) and plasma OPN in TB group at TBDx compared to the CTRL group. Inflammatory markers including IL-6, VEGF-A, and sFasL showed significant increase at TBDx when compared to CTRL, but these significantly declined by TBM6. Plasma OPN significantly declined at TBW1 and TBM2 when compared to TBDx but significantly increased at TBM6. BAL OPN showed no significant differences between CTRL and TB patients at TBDx, whereas a significant increase was observed in TB group between TBDx and TBM6. Given the study limitations, these findings should be considered preliminary and exploratory. Our results add to literature and identify MLR and plasma OPN as potential targets for early TB diagnosis and treatment monitoring.
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The authors thank the participants and members of the Immunology Research Group for providing the samples.
Funding
AGL and BM is funded by the Centre for Tuberculosis Research (CTR) of the South African Medical Research Council (SAMRC). AGL is supported by the National Research Foundation (NRF) [CSUR Grant number 60502163639] and by the Trails of Excellence in Southern Africa (TESA) III of the European Development and Clinical Trails Partnership (EDCTP) [Grant number CSA2020NoE-3104].
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Conceptualization, A.G.L.; methodology, B.M., A.H., C.I.S., and I.R.; formal analysis, K.S.; writing—original draft preparation, B.M. and A.H.; writing—review and editing, K.S., I.R., C.I.S; supervision, A.G.L.; funding acquisition, A.G.L. All authors have read and agreed to the published version of the manuscript.
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Motaung, B., Holtzhausen, AR., Stanley, K. et al. The value of the monocyte-to-lymphocyte ratio and osteopontin (SPP1) in tuberculosis treatment response monitoring. Sci Rep (2026). https://doi.org/10.1038/s41598-026-46176-8
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DOI: https://doi.org/10.1038/s41598-026-46176-8


