Difery Minadzi, Augustine Yeboah, Millicent Lamptey, Monika M Vivekanandan, Joseph F Arthur, Hubert S Ahor, Wilfred Aniagyei, Samuel A Sakyi, Anthony A A Awuah, Rejoice A Arthur, Victoria A Ofori, Albert D Kegya, Linda A Amoakoa, Ernest Adankwah, Dorcas O Owusu, Ijeoma C Anyitey-Kokor, Mohammed K Abass, Fredrick G Apraku, Nana K Ayisi-Boateng, Seth Adane, Salisu Zakaria, Ertan Mayatepek, Julia Seyfarth, Richard O Phillips, Marc Jacobsen
{"title":"An impaired T-cell-mediated mitogen response as a potential biomarker to aid in clinical diagnosis of pulmonary tuberculosis.","authors":"Difery Minadzi, Augustine Yeboah, Millicent Lamptey, Monika M Vivekanandan, Joseph F Arthur, Hubert S Ahor, Wilfred Aniagyei, Samuel A Sakyi, Anthony A A Awuah, Rejoice A Arthur, Victoria A Ofori, Albert D Kegya, Linda A Amoakoa, Ernest Adankwah, Dorcas O Owusu, Ijeoma C Anyitey-Kokor, Mohammed K Abass, Fredrick G Apraku, Nana K Ayisi-Boateng, Seth Adane, Salisu Zakaria, Ertan Mayatepek, Julia Seyfarth, Richard O Phillips, Marc Jacobsen","doi":"10.1007/s15010-026-03021-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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<sub>high</sub>) or low (pTB<sub>low</sub>) Mtb sputum load, and clinically diagnosed patients without Mtb confirmation (pTB<sub>clin</sub>). pTB patient subgroups were then compared with healthy contacts (controls; n = 49) for their immune responses to Mtb antigens (i.e. PPD<sub>Mtb</sub>, ESAT6/CFP10), the mitogen phytohemagglutinin, and a superantigen.</p><p><strong>Results: </strong>About half of the pTB patients were pTB<sub>clin</sub> (n = 41; 49.4%), while pTB<sub>high</sub> accounted for only about one-third (n = 26; 31.3%) and pTB<sub>low</sub> for about one-fifth (n = 16; 19.3%). Antigen-specific CD4<sup>+</sup> T-cell responses varied among the pTB subgroups, and only the pTB<sub>high</sub> group had higher IFNγ<sup>+</sup>/TNFα<sup>+</sup> T-cell proportions as compared to controls (PPD<sub>Mtb</sub>, p = 0.0003; ESAT6/CFP10, p < 0.0001). In contrast, phytohemagglutinin induced significantly lower proportions of CD4<sup>+</sup> T cells in all TB subgroups (pTB<sub>high</sub>, p < 0.0001; pTB<sub>low</sub>, p = 0.0039; pTB<sub>clin</sub>, p = 0.0012 for IFNγ<sup>+</sup>/TNFα<sup>+</sup>) and this measurement distinguished patient subgroups effectively from controls (pTB<sub>high</sub>, p < 0.0001; pTB<sub>low</sub>, p = 0.0132; pTB<sub>clin</sub>, p = 0.0006 for TNFα<sup>+</sup>/CD40L<sup>+</sup>). Finally, TNFα<sup>+</sup>/CD40L<sup>+</sup> T-cell responses to phytohemagglutinine had the highest efficiency to distinguish pTB<sub>clin</sub> with severe lung manifestation from controls (AUC = 0.9; p < 0.0001; 95%CI:0.82-0.98).</p><p><strong>Conclusion: </strong>This study underscores the importance of clinical pTB diagnosis and identifies a reduced T-cell cytokine response to phytohemagglutinin as a potential biomarker.</p>","PeriodicalId":13600,"journal":{"name":"Infection","volume":" ","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Infection","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s15010-026-03021-4","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
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 (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.
期刊介绍：
Infection is a journal dedicated to serving as a global forum for the presentation and discussion of clinically relevant information on infectious diseases. Its primary goal is to engage readers and contributors from various regions around the world in the exchange of knowledge about the etiology, pathogenesis, diagnosis, and treatment of infectious diseases, both in outpatient and inpatient settings.
The journal covers a wide range of topics, including:
Etiology: The study of the causes of infectious diseases.
Pathogenesis: The process by which an infectious agent causes disease.
Diagnosis: The methods and techniques used to identify infectious diseases.
Treatment: The medical interventions and strategies employed to treat infectious diseases.
Public Health: Issues of local, regional, or international significance related to infectious diseases, including prevention, control, and management strategies.
Hospital Epidemiology: The study of the spread of infectious diseases within healthcare settings and the measures to prevent nosocomial infections.
In addition to these, Infection also includes a specialized "Images" section, which focuses on high-quality visual content, such as images, photographs, and microscopic slides, accompanied by brief abstracts. This section is designed to highlight the clinical and diagnostic value of visual aids in the field of infectious diseases, as many conditions present with characteristic clinical signs that can be diagnosed through inspection, and imaging and microscopy are crucial for accurate diagnosis. The journal's comprehensive approach ensures that it remains a valuable resource for healthcare professionals and researchers in the field of infectious diseases.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
