{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T07:19:22Z","timestamp":1784791162556,"version":"3.55.0"},"posted":{"date-parts":[[2026,5,14]]},"group-title":"Immunology","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Tuberculosis (TB) continues to pose a significant global public health challenge with substantial patient morbidity and mortality. Current TB patient biomarkers lack sufficient resolution to inform treatment response and patient stratification. This necessitates the development of sensitive and reliable host biomarkers. We previously demonstrated the efficacy of TruCulture whole blood stimulation for differentiating asymptomatic TB from active pulmonary TB disease patients in endemic regions. Our systems immunology study expands upon this previous work by evaluating the potential of TruCulture to monitor longitudinal responses to TB treatment in patients from the Predict-TB trial before, during, and after 6 months of antibiotic therapy. We stimulated whole blood from TB patients (n=40) using TruCulture under four conditions (Null,\n                  <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                  -antigen, LPS, and IL-1\u03b2) at baseline (week 0), during treatment (weeks 16 and 24), and one-year follow-up post- treatment (week 72). 20\/25 measured cytokines exhibited significant changes throughout treatment, with several continuing to evolve during post-therapy follow-up. Machine learning based analysis identified\n                  <jats:italic>Mtb<\/jats:italic>\n                  -Ag-induced IL-1RA (AUC = 0.90, 0.92, 0.95 at weeks 16, 24, 72) and LPS-induced\n                  <jats:italic>NLRP3<\/jats:italic>\n                  (AUC = 0.94 at week 16) as the best protein and transcriptional biomarkers for distinguishing treated from untreated patients, strongly implicating the inflammasome response. Combining these results with the extent of lung disease assessed by FDG PET\/CT scans, we showed direct disease relevance for these blood-based biomarkers. The identified biomarker profiles hold promise for improving TB patient care through early prediction of treatment responses, real-time therapy monitoring, and informed development of host-directed therapeutic strategies for clinical decision-making.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Graphical abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" fig-type=\"figure\" orientation=\"portrait\">\n                    <jats:label>Graphical abstract<\/jats:label>\n                    <jats:caption>\n                      <jats:title>Predict-TB clinical study overview and summary of TB-specific biomarkers identified from TruCulture whole blood stimulation system.<\/jats:title>\n                    <\/jats:caption>\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"723467v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.07.723467","type":"posted-content","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T14:39:44Z","timestamp":1778769584000},"source":"Crossref","is-referenced-by-count":0,"title":["Integration of functional immunomonitoring assays with PET\/CT scans in TB patients identifies on-treatment biomarkers"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5713-9722","authenticated-orcid":false,"given":"Jingwen","family":"Fan","sequence":"first","affiliation":[{"name":"Translational Immunology Unit, Institut Pasteur ; 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Universit\u00e9 Paris Cit\u00e9, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Bondet","sequence":"additional","affiliation":[{"name":"Translational Immunology Unit, Institut Pasteur ; Universit\u00e9 Paris Cit\u00e9, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Jasper","sequence":"additional","affiliation":[{"name":"Translational Immunology Unit, Institut Pasteur ; Universit\u00e9 Paris Cit\u00e9, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Yu","sequence":"additional","affiliation":[{"name":"Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanus","family":"Malherbe","sequence":"additional","affiliation":[{"name":"DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Immunology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9906-0024","authenticated-orcid":false,"given":"Rapha\u00ebl","family":"Borie","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM, PHERE, H\u00f4pital Bichat, AP-HP, Service de Pneumologie A, Centre Constitutif du Centre de R\u00e9f\u00e9rence des Maladies Pulmonaires Rares, FHU APOLLO, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Peiffer-Smadja","sequence":"additional","affiliation":[{"name":"Service des Maladies Infectieuses et Tropicales, AP-HP, H\u00f4pital Bichat-Claude Bernard, Paris, France ; 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