Identification of candidate host serum and saliva biomarkers for a better diagnosis of active and latent tuberculosis infection

Abstract

In our work, we aim to identify new candidate host biomarkers to discriminate between active TB patients (n = 28), latent infection (LTBI; n = 27) and uninfected (NoTBI; n = 42) individuals. For that, active TB patients and their contacts were recruited that donated serum and saliva samples. A multiplex assay was performed to study the concentration of different cytokines, chemokines and growth factors. Proteins with significant differences between groups were selected and logistic regression and the area under the ROC curve (AUC) was used to assess the diagnostic accuracy. The best marker combinations that discriminate active TB from NoTBI contacts were [IP-10 + IL-7] in serum and [Fractalkine + IP-10 + IL-1α + VEGF] in saliva. Best discrimination between active TB and LTBI was achieved using [IP-10 + BCA-1] in serum (AUC = 0.83) and IP-10 in saliva (p = 0.0007; AUC = 0.78). The levels of TNFα (p = 0.003; AUC = 0.73) in serum and the combination of [Fractalkine +IL-12p40] (AUC = 0.83) in saliva, were able to differentiate between NoTBI and LTBI contacts. In conclusion, different individual and combined protein markers could help to discriminate between active TB and both uninfected and latently-infected contacts. The most promising ones include [IP-10 + IL-7], [IP-10 + BCA-1] and TNFα in serum and [Fractalkine + IP-10 + IL-1α + VEGF], IP-10 and [Fractalkine+IL-12p40] in saliva.

Human Saliva as a Diagnostic Specimen for Early Detection of Inflammatory Biomarkers by Real-Time RT-PCR

“…The advent of an effective and reliable salivary biomarker would undoubtedly meet the urgent need for a noninvasive means of detecting and monitoring HD disease progression [9]. Another recent report states that the best marker combination which includes inflammatory cytokines that differentiated active TB (tuberculosis) from healthy controls were fractalkine + IP-10 + IL-1α + VEGF in saliva [12]. The higher salivary concentrations of IL-17A, IL-17F, and TNF-α were significantly associated with disease advancement in patients with oral and oropharyngeal cancer.…”

Host-Based Biomarkers in Saliva for the Diagnosis of Pulmonary Tuberculosis in Children: A Mini-Review

“…Crucially, six biomarkers showed opposing trends between studies. For example, IP-10 was higher in TB patients in one study ( 46 ) whereas it was higher in healthy controls in another ( 45 ). Only salivary CRP and fraktaline showed a similar pattern across studies and were raised in TB cases in more than one study.…”

“…We found nine studies on host salivary diagnostic biomarkers, published between 1973 and 2021. Since only one study involved children (41), we also reviewed the evidence from eight adult studies (30,(42)(43)(44)(45)(46)(47)(48). Supplementary Figure 1 outlines the search procedure and Supplementary Table 1 summarizes the included studies.…”

“…Five studies measured salivary levels of selected cytokines, growth factors, enzymes and acute phase proteins in adults with confirmed TB or symptoms of TB using Luminex multiplex assays (30,(43)(44)(45)(46). Of the 54 biomarkers analyzed in more than one study, eight showed statistically significant differences (p < 0.05) between TB patients and negative controls, albeit only one study reported correction for multiple comparisons (46).…”

“…Five studies measured salivary levels of selected cytokines, growth factors, enzymes and acute phase proteins in adults with confirmed TB or symptoms of TB using Luminex multiplex assays (30,(43)(44)(45)(46). Of the 54 biomarkers analyzed in more than one study, eight showed statistically significant differences (p < 0.05) between TB patients and negative controls, albeit only one study reported correction for multiple comparisons (46). These eight biomarkers included alpha 2 macroglobulin (A2M), serum amyloid P (SAP), interferon gamma-induced protein (IP-10), vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), fraktaline, and c-reactive protein (CRP).…”