{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:59:48Z","timestamp":1790315988494,"version":"4.1.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"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. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The neutrophil CD64 (nCD64) index has emerged as a promising biomarker for infection detection, but its evaluation within the mycobacterial infection spectrum remains limited. Here, we evaluated the diagnostic and treatment response performance of the nCD64 index in the active tuberculosis (ATB)\u2014including pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (ePTB), and non-tuberculous mycobacterial (NTM) disease, and determined whether it adds value beyond standard inflammatory indicators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We measured the nCD64 index in a cross-sectional cohort comprising 248 participants across five groups: ATB, latent tuberculosis infection (LTBI), NTM, bacterial pulmonary infection (PI) and healthy donors (HD). Patients with ATB and NTM had not received anti-mycobacterial treatment at the time of enrollment. Diagnostic performance was assessed by receiver operating characteristic (ROC) curve analysis, and incremental value beyond white blood cell (WBC) count and C-reactive protein (CRP) was evaluated by comparing an area under the curve (AUC) with and without nCD64 index. In a separate longitudinal cohort of 244 participants, nCD64 index was measured at baseline and months 1\u20133 of anti-mycobacterial therapy, and longitudinal trajectories were compared between treatment-naive and retreatment patients using a linear mixed-effects (LME) model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      nCD64 index was markedly elevated in ATB compared to all other groups (all\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). It discriminated ATB from LTBI with an AUC of 0.739 and PTB from NTM with an AUC of 0.744. Addition of nCD64 index to WBC count significantly improved AUC in four diagnostic comparisons with gains of 0.12 to 0.34, most markedly for PTB versus PI. nCD64 index was significantly higher in PTB than NTM (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001) with limited stratification by clinical features. In the longitudinal cohort, nCD64 index declined progressively from month 1 in both PTB and NTM patients and remained lower through month 3. Treatment-naive patients exhibited significantly steeper decline trajectories than retreatment patients (PTB\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001, NTM\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.004).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The nCD64 index discriminates ATB from LTBI and NTM, adds diagnostic value beyond routine inflammatory markers, and tracks serial changes during treatment in both ATB and NTM. Treatment-naive patients showed more pronounced decline trajectories, supporting particular utility of the nCD64 index for tracking initial treatment response. It warrants further evaluation as a complementary biomarker in the clinical management of mycobacterial infections.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1980277","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:31:45Z","timestamp":1790314305000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neutrophil CD64 index for diagnosing and tracking treatment response across the mycobacterial infection spectrum: a retrospective two-cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuxi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yankun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyou","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaocui","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"4065","DOI":"10.1007\/s11033-020-05413-7","article-title":"Advances in diagnosis of tuberculosis: an update into molecular diagnosis of Mycobacterium tuberculosis","volume":"47","author":"Acharya","year":"2020","journal-title":"Mol. Biol. Rep."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1086\/431680","article-title":"In tuberculous pleural effusions, activated neutrophils undergo apoptosis and acquire a dendritic cell\u2013like phenotype","volume":"192","author":"Alem\u00e1n","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s12941-023-00562-6","article-title":"The roles of neutrophils in non-tuberculous mycobacterial pulmonary disease","volume":"22","author":"Alkarni","year":"2023","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1038\/nature09247","article-title":"An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis","volume":"466","author":"Berry","year":"2010","journal-title":"Nature"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1002\/iid3.289","article-title":"Role of the interferons in CD64 and CD169 expressions in whole blood: relevance in the balance between viral- or bacterial-oriented immune responses","volume":"8","author":"Bourgoin","year":"2020","journal-title":"Immun. Inflamm. Dis."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1186\/s12887-022-03738-9","article-title":"Neutrophil CD64 index for diagnosis of infectious disease in the pediatric ICU: a single-center prospective study","volume":"22","author":"Cao","year":"2022","journal-title":"BMC Pediatr."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e180579","DOI":"10.1590\/0074-02760180579","article-title":"Neutrophil CD64 expression levels in IGRA-positive individuals distinguish latent tuberculosis from active disease","volume":"114","author":"Corr\u00eaa","year":"2019","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.21037\/tp-21-63","article-title":"Assessment of continuous neutrophil CD64 index measurement for diagnosing sepsis and predicting outcome in a Chinese pediatric intensive care unit: a prospective study","volume":"10","author":"Cui","year":"2021","journal-title":"Transl. Pediatr."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1093\/cid\/ciaa241","article-title":"Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS\/ERS\/ESCMID\/IDSA clinical practice guideline","volume":"71","author":"Daley","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1093\/cid\/cit936","article-title":"Serial determinations of neutrophil CD64 expression for the diagnosis and monitoring of Sepsis in critically ill patients","volume":"58","author":"Dimoula","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s13690-020-0393-6","article-title":"Tuberculosis treatment outcome among patients treated in public primary healthcare facility, Addis Ababa, Ethiopia: a retrospective study","volume":"78","author":"Fentie","year":"2020","journal-title":"Arch. Public Health"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"2580695","DOI":"10.1080\/19420862.2025.2580695","article-title":"Extracellular domain 1 of human Fc\u03b3RI (CD64) identified as the binding site for anti-Fc\u03b3RI antibodies","volume":"17","author":"Holtrop","year":"2025","journal-title":"MAbs"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1186\/s12967-024-04901-9","article-title":"Neutrophil CD64 index as a new early predictive biomarker for infected pancreatic necrosis in acute pancreatitis","volume":"22","author":"Huang","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"3914","DOI":"10.1128\/JCM.00628-09","article-title":"CD64 index provides simple and predictive testing for detection and monitoring of sepsis and bacterial infection in hospital patients","volume":"47","author":"Icardi","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"e1005490","DOI":"10.1371\/journal.ppat.1005490","article-title":"TIM3 mediates T cell exhaustion during Mycobacterium tuberculosis infection","volume":"12","author":"Jayaraman","year":"2016","journal-title":"PLoS Pathog."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"770","DOI":"10.3109\/14397595.2013.871108","article-title":"Neutrophil CD64 for monitoring the activity of nontuberculous mycobacteria infection in patients with rheumatoid arthritis","volume":"24","author":"Komiya","year":"2014","journal-title":"Mod. Rheumatol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"R6","DOI":"10.1186\/ar2590","article-title":"Increased expression of Fc\u03b3RI\/CD64 on circulating monocytes parallels ongoing inflammation and nephritis in lupus","volume":"11","author":"Li","year":"2009","journal-title":"Arthritis Res. Ther."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1706786","DOI":"10.3389\/fmicb.2026.1706786","article-title":"Neutrophil CD64 index for rapid diagnosis of Pneumocystis jirovecii pneumonia in malignancy patients requiring mechanical ventilation: a retrospective analysis","volume":"17","author":"Li","year":"2026","journal-title":"Front. Microbiol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"13961","DOI":"10.1111\/jcmm.16004","article-title":"Differential expression of CD64 in patients with Mycobacterium tuberculosis infection: a potential biomarker for clinical diagnosis and prognosis","volume":"24","author":"Liu","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"905060","DOI":"10.3389\/fimmu.2022.905060","article-title":"nCD64 index as a novel inflammatory indicator for the early prediction of prognosis in infectious and non-infectious inflammatory diseases: an observational study of febrile patients","volume":"13","author":"Liu","year":"2022","journal-title":"Front. Immunol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"2460","DOI":"10.3390\/microorganisms9122460","article-title":"T-cell exhaustion in Mycobacterium tuberculosis and nontuberculous mycobacteria infection: pathophysiology and therapeutic perspectives","volume":"9","author":"Lombardi","year":"2021","journal-title":"Microorganisms"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"6843","DOI":"10.4103\/jfmpc.jfmpc_2296_21","article-title":"Analysis of CD4, CD8, CD19, CD56-16, CD64, QuantiFERON biomarkers in exudative lymphocyte-dominant pleural effusion","volume":"11","author":"Mehraban","year":"2022","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"26884","DOI":"10.1038\/s41598-024-77164-5","article-title":"Specific human gene expression in response to infection is an effective marker for diagnosis of latent and active tuberculosis","volume":"14","author":"Nakiboneka","year":"2024","journal-title":"Sci. Rep."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"e00258","DOI":"10.1128\/cmr.00258-25","article-title":"From T-cell sensitization to molecular\u2013intelligent stratification: a roadmap for precision diagnosis of latent tuberculosis infection","volume":"39","author":"Ni","year":"2026","journal-title":"Clin. Microbiol. Rev."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1183\/13993003.01012-2016","article-title":"Correlates of tuberculosis risk: predictive biomarkers for progression to active tuberculosis","volume":"48","author":"Petruccioli","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"303","DOI":"10.3389\/fimmu.2020.00303","article-title":"The rise of non-tuberculosis mycobacterial lung disease","volume":"11","author":"Ratnatunga","year":"2020","journal-title":"Front. Immunol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"729","DOI":"10.3238\/arztebl.2019.0729","article-title":"The diagnosis and treatment of tuberculosis","volume":"116","author":"Su\u00e1rez","year":"2019","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref28","volume-title":"Global Tuberculosis Report 2025","year":"2025"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1186\/s13075-025-03611-x","article-title":"nCD64 index as a new early predictive biomarker for macrophage activation syndrome in adult-onset still\u2019s disease","volume":"27","author":"Wu","year":"2025","journal-title":"Arthritis Res. Ther."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"115178","DOI":"10.1016\/j.isci.2026.115178","article-title":"Multidimensional cfRNA response modeling identifies a 5-gene pair signature for high-robust pulmonary tuberculosis diagnosis","volume":"29","author":"Wu","year":"","journal-title":"iScience"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"2261561","DOI":"10.1080\/22221751.2023.2261561","article-title":"Assessment of the cepheid 3-gene host response fingerstick blood test (MTB-HR) on rapid diagnosis of tuberculosis","volume":"12","author":"Wu","year":"2023","journal-title":"Emerg. Microbes Infect."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1186\/s12915-026-02585-9","article-title":"PTBD: a machine learning-based non-invasive diagnostic model for pulmonary tuberculosis using large-scale blood transcriptomes","volume":"24","author":"Wu","year":"","journal-title":"BMC Biol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"2312","DOI":"10.1016\/S0140-6736(15)01316-1","article-title":"A prospective blood RNA signature for tuberculosis disease risk","volume":"387","author":"Zak","year":"2016","journal-title":"Lancet"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1980277\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:31:46Z","timestamp":1790314306000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1980277\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,25]]},"references-count":33,"alternative-id":["10.3389\/fmicb.2026.1980277"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1980277","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,25]]},"article-number":"1980277"}}