Differential Expression of Host Biomarkers in Saliva and Serum Samples from Individuals with Suspected Pulmonary Tuberculosis

Abstract

The diagnosis of tuberculosis remains challenging in individuals with difficulty in providing good quality sputum samples such as children. Host biosignatures of inflammatory markers may be valuable in such cases, especially if they are based on more easily obtainable samples such as saliva. To explore the potential of saliva as an alternative sample in tuberculosis diagnostic/biomarker investigations, we evaluated the levels of 33 host markers in saliva samples from individuals presenting with pulmonary tuberculosis symptoms and compared them to those obtained in serum. Of the 38 individuals included in the study, tuberculosis disease was confirmed in 11 (28.9%) by sputum culture. In both the tuberculosis cases and noncases, the levels of most markers were above the minimum detectable limit in both sample types, but there was no consistent pattern regarding the ratio of markers in serum/saliva. Fractalkine, IL-17, IL-6, IL-9, MIP-1β, CRP, VEGF, and IL-5 levels in saliva and IL-6, IL-2, SAP, and SAA levels in serum were significantly higher in tuberculosis patients (P < 0.05). These preliminary data indicate that there are significant differences in the levels of host markers expressed in saliva in comparison to those expressed in serum and that inflammatory markers in both sample types are potential diagnostic candidates for tuberculosis disease.

Update on tuberculosis biomarkers: From correlates of risk, to correlates of active disease and of cure from disease

“…It has been reported that saliva levels of interleukin (IL)-1β, IL-23, ECM-1, HCC1 and fibrinogen are significantly associated with active TB. 53,54 One study 55 showed that some host inflammatory BM were expressed at much higher concentrations in saliva than in the blood.…”

T cells and adaptive immunity to Mycobacterium tuberculosis in humans

“…Active TB is characterized by inflammation and the upregulation of acute phase proteins, cytokines, chemokines, and matrix metalloproteinases (MMPs) , which in turn can affect T‐cell function and development in the blood, sputum, and at sites of disease. Cavitation, which is a hallmark of adult pulmonary TB disease, is driven by elevated expression of inflammatory matrix metalloproteinase‐1 (MMP‐1) and MMP‐3, which are found at greater levels in sputum and bronchoalveolar lavage fluid from patients with active TB .…”

Diagnostic performance of a seven-marker serum protein biosignature for the diagnosis of active TB disease in African primary healthcare clinic attendees with signs and symptoms suggestive of TB

“…There is an urgent need for alternative diagnostic tests that are suitable for use in all patient types, especially in resource-poor settings. Tests based on the detection of host inflammatory molecules5 6 may be beneficial, especially when applied to easily available samples such as finger-prick blood or serum.…”