{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T08:14:28Z","timestamp":1767946468107,"version":"3.49.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To evaluate the diagnostic value of a combined strategy using the urine lipoarabinomannan (LAM) antigen assay and interferon-gamma release assay (IGRA) for active tuberculosis (TB), and to explore its potential as a non-invasive, sputum-independent diagnostic method for clinical application.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>A cross-sectional study design was adopted. Initially, 313 valid cases were selected for LAM performance evaluation, subsequently, 142 cases with both valid LAM and IGRA results were further selected from this group for combined test performance analysis. Using comprehensive clinical diagnosis as the reference standard, the diagnostic performance of LAM, IGRA, and two combination strategies (parallel: positive if either LAM or IGRA is positive; serial: positive only if both are positive) was evaluated, and their distribution characteristics in differentiating between tuberculosis and nontuberculous mycobacterial (NTM) infection were preliminarily explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The urine LAM assay demonstrated a sensitivity of 72% and a specificity of 79% for active TB. Its sensitivity was higher than that of smear microscopy (33%) and culture (56%), and slightly superior to Xpert MTB\/RIF (69%) and TB-DNA (65%), although its specificity was lower. IGRA showed high sensitivity (92%) but moderate specificity (59%). The combination of LAM and IGRA significantly improved diagnostic performance: parallel testing achieved a sensitivity of 98%, making it suitable for TB screening and rule-out purposes, while serial testing increased specificity to 91%, supporting the confirmatory diagnosis of active TB. Among patients with NTM infection, the LAM\n                      <jats:sup>+<\/jats:sup>\n                      \/IGRA\n                      <jats:sup>\u2212<\/jats:sup>\n                      pattern accounted for 50% of cases, suggesting its potential utility in discriminating between TB and NTM infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The combination of urine LAM antigen testing and blood-based IGRA optimizes TB diagnosis by simultaneously targeting two distinct dimensions: pathogen-derived antigens and host immune response. The parallel testing improves sensitivity for screening, while the serial testing enhances specificity for confirmatory diagnosis. This strategy offers a non-invasive approach with ease of sample collection, demonstrating particular value in diagnosing challenging cases such as sputum smear-negative pulmonary TB, extrapulmonary TB, and TB in immunocompromised patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1726930","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T06:36:52Z","timestamp":1767940612000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A novel non-invasive diagnostic approach based on urine and blood: a cross-sectional study combining lipoarabinomannan antigen and interferon-gamma release assay for active tuberculosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Long","family":"Cai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingzhi","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianqian","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingshan","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"YanQin","family":"Shao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Libin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"B1","unstructured":"Global TB report 2024[EB\/OL]\n          \n          2024"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01582-19","article-title":"Advances in molecular diagnosis of TB","volume":"58","author":"MacLean","year":"2020","journal-title":"J Clin Microbiol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"41","DOI":"10.2174\/1874285801812010041","article-title":"Mycobacteriosis and TB: laboratory diagnosis","volume":"12","author":"Azadi","year":"2018","journal-title":"Open Microbiol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD009593","article-title":"Xpert MTB\/RIF and Xpert MTB\/RIF Ultra for pulmonary TB and rifampicin resistance in adults","volume":"6","author":"Horne","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"key":"B5","unstructured":"The end TB strategy [EB\/OL]. [2015-08 -16]"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm","article-title":"Rapid detection of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells","volume":"163","author":"Lalvani","year":"2001","journal-title":"Am J Respir Crit Care Med"},{"key":"B7","first-page":"1","article-title":"Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection - United States, 2010","volume":"59","author":"Mazurek","year":"2010","journal-title":"MMWR Recomm Rep"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202007-2686OC","article-title":"Antigen-specific T-cell activation distinguishes between recent and remote TB infection","volume":"203","author":"Mpande","year":"2021","journal-title":"Am J Respir Crit Care Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00115-2018","article-title":"Biomarkers for TB: the case for LAM","volume":"5","author":"Correia-Neves","year":"2019","journal-title":"ERJ Open Res"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9010111","article-title":"Point-of-care urine LAM tests for TB diagnosis: a status update","volume":"9","author":"Bulterys","year":"2019","journal-title":"J Clin Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.638047","article-title":"LAM as a point-of-care assay for diagnosis of TB: how far are we to use it","volume":"12","author":"Flores","year":"2021","journal-title":"Front Microbiol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1172\/JCI140461","article-title":"Diagnostic accuracy of 3 urine LAM TB assays in HIV-negative outpatients","volume":"130","author":"Broger","year":"2020","journal-title":"J Clin Invest"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2025.1498651","article-title":"A new strategy improving TB diagnosis: stratified urine LAM test based on lymphocyte counts","volume":"15","author":"Li","year":"2025","journal-title":"Front Cell Infect Microbiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.19871\/j.cnki.xfcrbzz.2018.03.018","article-title":"TB classification (WS196-2017)","volume":"3","year":"2018","journal-title":"Electron J Emerg Infect Dis"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/ice.2024.214","article-title":"TB or not TB? Development and validation of a clinical decision support system to inform airborne isolation requirements in the evaluation of suspected TB","volume":"46","author":"Dugdale","year":"2025","journal-title":"Infect Control Hosp Epidemiol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e14088","DOI":"10.15252\/emmm.202114088","article-title":"Diagnostic biomarkers for active TB: progress and challenges","volume":"14","author":"Nogueira","year":"2022","journal-title":"EMBO Mol Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaf110","article-title":"Improved detection of extrapulmonary and paucibacillary pulmonary TB by xpert MTB host response in a TB low-endemic, high-resource setting","volume":"232","author":"Folkesson","year":"2025","journal-title":"J Infect Dis"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1291974","article-title":"Diagnostic value of chemiluminescence for urinary LAM antigen assay in active TB: insights from a retrospective study","volume":"13","author":"Huang","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.tube.2019.02.008","article-title":"A paucity of knowledge regarding nontuberculous mycobacterial lipids compared to the tubercle bacillus","volume":"115","author":"Tran","year":"2019","journal-title":"TB (Edinb)"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e0003891","DOI":"10.1371\/journal","article-title":"Urine LAM concentrations among HIV-negative adults with pulmonary or EPTB disease in Vietnam","volume":"4","author":"Hoa","year":"2024","journal-title":"PloS Glob Public Health"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00115-2018","article-title":"Biomarkers for TB: the case for LAM","volume":"5","author":"Correia-Neves","year":"2019","journal-title":"ERJ Open Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1172\/JCI140461","article-title":"Diagnostic accuracy of 3 urine LAM TB assays in HIV-negative outpatients","volume":"130","author":"Broger","year":"2020","journal-title":"J Clin Invest"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1726930\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T06:36:55Z","timestamp":1767940615000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1726930\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,9]]},"references-count":22,"alternative-id":["10.3389\/fimmu.2025.1726930"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1726930","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,9]]},"article-number":"1726930"}}