Evaluation of cytokines in peripheral blood mononuclear cell supernatants for the diagnosis of tuberculosis
Received 13 August 2018
Accepted for publication 16 October 2018
Published 24 December 2018 Volume 2019:12 Pages 15—22
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 3
Editor who approved publication: Dr Ning Quan
Margaretha Sariko,1–3 Athanasia Maro,1,3 Jean Gratz,1,4 Eric Houpt,4 Riziki Kisonga,1,5 Stellah Mpagama,1,5 Scott Heysell,4 Blandina T Mmbaga,1–3,* Tania A Thomas4,*
1Kilimanjaro Clinical Research Institute, Moshi, Tanzania; 2Kilimanjaro Christian Medical University College, Moshi, Tanzania; 3Kilimanjaro Christian Medical Centre, Moshi, Tanzania; 4Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, VA, USA; 5Kibong’oto Infectious Diseases Hospital, Kilimanjaro, Tanzania
*These authors contributed equally to this work
Introduction: There is active interest in leveraging host immune responses as biomarkers of tuberculosis (TB) disease activity. We had previously evaluated an immunodiagnostic test called the antibody in lymphocyte supernatant (ALS) assay. Here, we aimed to evaluate a panel of inflammatory mediators and associate the responses with the ALS results to identify a biosignature to distinguish TB cases from controls.
Methodology: In this case–control study, adults with TB were compared to controls who were hospitalized for non-infectious conditions. Blood was collected at baseline and after 4 weeks of TB treatment (from TB cases only). Peripheral blood mononuclear cells were isolated and cultured without antigenic stimulation for 72 hours. Inflammatory mediators were measured using the Multiplex cytokine kit and compared between TB cases and controls; among TB cases, responses were compared over time. ALS and inflammatory mediator results were evaluated using generalized discriminant analysis to identify the optimal biosignature to predict TB.
Results: When comparing inflammatory mediators between groups, IL-1ra, IL-1β, and granulocyte macrophage-colony stimulating factor (GM-CSF) were lower in TB cases (P<0.002). Fibroblast growth factor-basic significantly increased from baseline to week-4 (P=0.002). Generalized discriminant analysis yielded a model with IL-2, tumor necrosis factor-alpha, vascular endothelial growth factor, and ALS, providing a sensitivity of 82.2% and specificity of 76.2%.
Conclusion: Our results suggest that IL-1ra, IL-1β, and GM-CSF might be used as diagnostic biomarkers to distinguish between TB cases and non-TB cases. We could not identify a group of mediators that outperformed the diagnostic accuracy of the ALS alone.
Keywords: cytokines, chemokines, biomarkers, TB, diagnostics
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