Infection · 2026
An impaired T-cell-mediated mitogen response as a potential biomarker to aid in clinical diagnosis of pulmonary tuberculosis.
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Minadzi Difery, Yeboah Augustine, Lamptey Millicent, Vivekanandan Monika M, Arthur Joseph F, Ahor Hubert S, Aniagyei Wilfred, Sakyi Samuel A, Awuah Anthony A A, Arthur Rejoice A, Ofori Victoria A, Kegya Albert D, Amoakoa Linda A, Adankwah Ernest, Owusu Dorcas O, Anyitey-Kokor Ijeoma C, Abass Mohammed K, Apraku Fredrick G, Ayisi-Boateng Nana K, Adane Seth, Zakaria Salisu, Mayatepek Ertan, Seyfarth Julia, Phillips Richard O, Jacobsen Marc
Аннотация
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 (pTBhigh) or low (pTBlow) Mtb sputum load, and clinically diagnosed patients without Mtb confirmation (pTBclin). pTB patient subgroups were then compared with healthy contacts (controls; n = 49) for their immune responses to Mtb antigens (i.e. PPDMtb, ESAT6/CFP10), the mitogen phytohemagglutinin, and a superantigen.
RESULTS: About half of the pTB patients were pTBclin (n = 41; 49.4%), while pTBhigh accounted for only about one-third (n = 26; 31.3%) and pTBlow for about one-fifth (n = 16; 19.3%). Antigen-specific CD4+ T-cell responses varied among the pTB subgroups, and only the pTBhigh group had higher IFNγ+/TNFα+ T-cell proportions as compared to controls (PPDMtb, p = 0.0003; ESAT6/CFP10, p < 0.0001). In contrast, phytohemagglutinin induced significantly lower proportions of CD4+ T cells in all TB subgroups (pTBhigh, p < 0.0001; pTBlow, p = 0.0039; pTBclin, p = 0.0012 for IFNγ+/TNFα+) and this measurement distinguished patient subgroups effectively from controls (pTBhigh, p < 0.0001; pTBlow, p = 0.0132; pTBclin, p = 0.0006 for TNFα+/CD40L+). Finally, TNFα+/CD40L+ T-cell responses to phytohemagglutinine had the highest efficiency to distinguish pTBclin 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.
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 (pTBhigh) or low (pTBlow) Mtb sputum load, and clinically diagnosed patients without Mtb confirmation (pTBclin). pTB patient subgroups were then compared with healthy contacts (controls; n = 49) for their immune responses to Mtb antigens (i.e. PPDMtb, ESAT6/CFP10), the mitogen phytohemagglutinin, and a superantigen.
RESULTS: About half of the pTB patients were pTBclin (n = 41; 49.4%), while pTBhigh accounted for only about one-third (n = 26; 31.3%) and pTBlow for about one-fifth (n = 16; 19.3%). Antigen-specific CD4+ T-cell responses varied among the pTB subgroups, and only the pTBhigh group had higher IFNγ+/TNFα+ T-cell proportions as compared to controls (PPDMtb, p = 0.0003; ESAT6/CFP10, p < 0.0001). In contrast, phytohemagglutinin induced significantly lower proportions of CD4+ T cells in all TB subgroups (pTBhigh, p < 0.0001; pTBlow, p = 0.0039; pTBclin, p = 0.0012 for IFNγ+/TNFα+) and this measurement distinguished patient subgroups effectively from controls (pTBhigh, p < 0.0001; pTBlow, p = 0.0132; pTBclin, p = 0.0006 for TNFα+/CD40L+). Finally, TNFα+/CD40L+ T-cell responses to phytohemagglutinine had the highest efficiency to distinguish pTBclin 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.