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In the absence of pathogen detection, supplementary indicators, such as immunological biomarkers, would facilitate TB diagnostic decision-making.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In this prospective case-control study conducted in Ghana, patients with suspected pTB (\n n<\/jats:italic>\n \u2009=\u200983) were divided into three subgroups: confirmed cases with high (pTB\n high<\/jats:sub>\n ) or low (pTB\n low<\/jats:sub>\n )\n Mtb<\/jats:italic>\n sputum load, and clinically diagnosed patients without\n Mtb<\/jats:italic>\n confirmation (pTB\n clin<\/jats:sub>\n ). pTB patient subgroups were then compared with healthy contacts (controls;\n n<\/jats:italic>\n \u2009=\u200949) for their immune responses to\n Mtb<\/jats:italic>\n antigens (i.e. PPD\n \n Mtb<\/jats:italic>\n <\/jats:sub>\n , ESAT6\/CFP10), the mitogen phytohemagglutinin, and a superantigen.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n About half of the pTB patients were pTB\n clin<\/jats:sub>\n (\n n<\/jats:italic>\n \u2009=\u200941; 49.4%), while pTB\n high<\/jats:sub>\n accounted for only about one-third (\n n<\/jats:italic>\n \u2009=\u200926; 31.3%) and pTB\n low<\/jats:sub>\n for about one-fifth (\n n<\/jats:italic>\n \u2009=\u200916; 19.3%). Antigen-specific CD4\n +<\/jats:sup>\n T-cell responses varied among the pTB subgroups, and only the pTB\n high<\/jats:sub>\n group had higher IFN\u03b3\n +<\/jats:sup>\n \/TNF\u03b1\n +<\/jats:sup>\n T-cell proportions as compared to controls (PPD\n Mtb<\/jats:sub>\n ,\n p<\/jats:italic>\n \u2009=\u20090.0003; ESAT6\/CFP10,\n p<\/jats:italic>\n \u2009<\u20090.0001). In contrast, phytohemagglutinin induced significantly lower proportions of CD4\n +<\/jats:sup>\n T cells in all TB subgroups (pTB\n high<\/jats:sub>\n ,\n p<\/jats:italic>\n \u2009<\u20090.0001; pTB\n low<\/jats:sub>\n ,\n p<\/jats:italic>\n \u2009=\u20090.0039; pTB\n clin<\/jats:sub>\n ,\n p<\/jats:italic>\n \u2009=\u20090.0012 for IFN\u03b3\n +<\/jats:sup>\n \/TNF\u03b1\n +<\/jats:sup>\n ) and this measurement distinguished patient subgroups effectively from controls (pTB\n high<\/jats:sub>\n ,\n p<\/jats:italic>\n \u2009<\u20090.0001; pTB\n low<\/jats:sub>\n ,\n p<\/jats:italic>\n \u2009=\u20090.0132; pTB\n clin<\/jats:sub>\n ,\n p<\/jats:italic>\n \u2009=\u20090.0006 for TNF\u03b1\n +<\/jats:sup>\n \/CD40L\n +<\/jats:sup>\n ). Finally, TNF\u03b1\n +<\/jats:sup>\n \/CD40L\n +<\/jats:sup>\n T-cell responses to phytohemagglutinine had the highest efficiency to distinguish pTB\n clin<\/jats:sub>\n with severe lung manifestation from controls (AUC\u2009=\u20090.9;\n p<\/jats:italic>\n \u2009<\u20090.0001; 95%CI:0.82\u20130.98).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n This study underscores the importance of clinical pTB diagnosis and identifies a reduced T-cell cytokine response to phytohemagglutinin as a potential biomarker.<\/jats:p>\n <\/jats:sec>","DOI":"10.1007\/s15010-026-03021-4","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T10:26:52Z","timestamp":1792405612000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An impaired T-cell-mediated mitogen response as a potential biomarker to aid in clinical diagnosis of pulmonary tuberculosis"],"prefix":"10.1007","author":[{"given":"Difery","family":"Minadzi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augustine","family":"Yeboah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Millicent","family":"Lamptey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika M.","family":"Vivekanandan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph F.","family":"Arthur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert S.","family":"Ahor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfred","family":"Aniagyei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel A.","family":"Sakyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony A. 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