Diagnostic Accuracy of Monocyte Chemotactic Protein (MCP)-2 as Biomarker in Response to PE35/PPE68 Proteins: A Promising Diagnostic Method for the Discrimination of Active and Latent Tuberculosis

Several studies have been conducted to find new biomarkers for the discrimination of Latent Tuberculosis Infection (LTBI) from active TB (ATB); however, their findings are inconsistent. The aim of the current study was to evaluate the potential of in vitro antigenspecific expression of Monocyte Chemotactic Protein (MCP)-2 for discrimination of ATB and LTBI after stimulation of whole blood with PE35 and PPE68 recombinant proteins.The recombinant PE35 and PPE68 proteins were evaluated at a final concentration of 5 µg/ml by a 3-day whole blood assay. Secreted MCP-2 from the culture supernatants were measured by commercially available Human MCP2 ELISA Kit. The diagnostic performance of MCP-2 was ascertained by Receiver Operator Characteristic (ROC) curve and measuring the Area Under the Curve (AUC) and their 95% Confidence Intervals (CI). Cut-offs was estimated at various sensitivities and specificities and at the maximum Youden's index (YI), i.e. sensitivity specificity-1.The median MCP-2 response to both PE35 and PPE68 in those with LTBI was significantly higher than patients with ATB. The discrimination performance of MCP-2 response following stimulation of PE35 (assessed by AUC) between LTBI and patients with ATB was 0.98 (95%CI: 0.94-1.00). Maximum discrimination was reached at a cut-off of 86pg/mL with 100% sensitivity and 97% specificity. The highest sensitivity and specificity was obtained using cut off 58 pg/mL following stimulation with PPE68 (100% and 90%, respectively; AUC: 0.94, 95%CI: 0.85- 1.00).MCP-2 induced by PE35 and PPE68 shows good discriminatory power for discrimination of ATB and LTBI. Additional studies with a larger sample size are needed to confirm the advantage of this marker, alone or combined with other markers; however, these findings present a promising method, which can discriminate between ATB and LTBI.