Novel plasma biomarkers for the diagnosis of pulmonary tuberculosis

The World Health Organization (WHO) has highlighted the need for new diagnostic tests for pulmonary tuberculosis (TB) that use easily obtainable samples, such as blood, to provide rapid and affordable results suitable for primary healthcare settings. To address this, we evaluated the diagnostic potential of 34 markers quantified by Luminex in supernatants of whole-blood cultures, either stimulated or not with an apolar lipid extract from Mycobacterium tuberculosis (Mtb). The study included 20 patients with pulmonary TB and 20 symptomatic respiratory (SR) non-TB individuals. In unstimulated cultures, eight biomarkers (IL-18, IL-1RA, IL-1β, IL-8, IP-10, MIP-1β, SDF-1α, and TNF-α) differentiated TB patients from SR - non-TB patients, with areas under the ROC curve (AUC) ranging from 0.71 to 0.82. Combinatorial analyses with four-marker panels, namely, IL-18 + IL-1β, IL-1RA + IL-18, IL-18 + IL-1β + IL-1RA and IL-18 + IL-1β + IL-1RA + MIP-1β, revealed AUCs of 0.84-0.90, specificities above 90 % and sensitivities between 70 % and 75 %. The addition of the lipid extract to the whole-blood culture did not improve the discriminatory power of the panels. Validation of the IL-1RA + IL-18 combination by ELISA in an independent group (21 TB patients and 33 SR patients) yielded an AUC of 0.76, a sensitivity of 62 %, a specificity of 88 %, and an accuracy of 78 %. The collective elevation of these cytokines suggests an interplay between pro- and anti-inflammatory pathways in the host response. Although the selected biomarker panels showed moderate diagnostic performance in the ELISA test, other combinations may be useful in helping to predict TB progression or monitor treatment outcomes.