An impaired T-cell-mediated mitogen response as a potential biomarker to aid in clinical diagnosis of pulmonary tuberculosis

Abstract Purpose A considerable proportion of suspected pulmonary tuberculosis (pTB) cases are identified and treated on the basis of clinical diagnoses, as it is often not possible to confirm Mycobacterium tuberculosis (Mtb) infection. In the absence of pathogen detection, supplementary indicators, such as immunological biomarkers, would facilitate TB diagnostic decision-making. Methods In this prospective case-control study conducted in Ghana, patients with suspected pTB ( n = 83) were divided into three subgroups: confirmed cases with high (pTB high ) or low (pTB low ) Mtb sputum load, and clinically diagnosed patients without Mtb confirmation (pTB clin ). pTB patient subgroups were then compared with healthy contacts (controls; n = 49) for their immune responses to Mtb antigens (i.e. PPD Mtb , ESAT6/CFP10), the mitogen phytohemagglutinin, and a superantigen. Results About half of the pTB patients were pTB clin ( n = 41; 49.4%), while pTB high accounted for only about one-third ( n = 26; 31.3%) and pTB low for about one-fifth ( n = 16; 19.3%). Antigen-specific CD4 + T-cell responses varied among the pTB subgroups, and only the pTB high group had higher IFNγ + /TNFα + T-cell proportions as compared to controls (PPD Mtb , p = 0.0003; ESAT6/CFP10, p < 0.0001). In contrast, phytohemagglutinin induced significantly lower proportions of CD4 + T cells in all TB subgroups (pTB high , p < 0.0001; pTB low , p = 0.0039; pTB clin , p = 0.0012 for IFNγ + /TNFα + ) and this measurement distinguished patient subgroups effectively from controls (pTB high , p < 0.0001; pTB low , p = 0.0132; pTB clin , p = 0.0006 for TNFα + /CD40L + ). Finally, TNFα + /CD40L + T-cell responses to phytohemagglutinine had the highest efficiency to distinguish pTB clin with severe lung manifestation from controls (AUC = 0.9; p < 0.0001; 95%CI:0.82–0.98). Conclusion This study underscores the importance of clinical pTB diagnosis and identifies a reduced T-cell cytokine response to phytohemagglutinin as a potential biomarker.