{ "abstract": "Background: Host-directed therapies may improve tuberculosis (TB) outcomes by modulating immune responses and attenuating hyperinflammation, yet accessible biomarkers remain limited. We hypothesized that interferon-γ–inducible protein 10 (IP-10/CXCL10) measured in dried blood spot (DBS), a low-threshold and field-adapted sampling method, has potential as a biomarker for treatment response in pulmonary TB. Accordingly, we assessed IP-10 levels in patients receiving adjunctive acetylsalicylic acid (ASA) or ibuprofen (IBU) alongside TB standard therapy.\n\nMethods: IP-10 levels were quantified longitudinally in DBS from 120 pulmonary TB patients enrolled in the SMA-TB clinical trial (NCT04575519) at two sites in South Africa. Samples collected at baseline, week 2, week 8, and week 24 were analyzed by the enzyme-linked immunosorbent assay (ELISA). Associations with disease severity and treatment response were assessed, and the predictive value of IP-10 for microbiological, clinical, and radiological outcomes was evaluated.\n\nResults: IP-10 levels correlated with TB disease severity, with higher concentrations observed in patients with elevated clinical and radiological scores and positive sputum acid-fast-bacilli staining. This association was reflected in treatment response, as patients with good clinical outcomes exhibited an earlier decline in IP-10 (week 8, p=0.0005), whereas those with poor outcomes showed a delayed decline (week 24, p<0.0001). Overall, IP-10 levels decreased during treatment irrespective of intervention or HIV status, with no significant differences between treatment arms at week 24. Notably, IP-10 levels at week 2 predicted rapid sputum culture conversion in the IBU arm, as well as in HIV-negative patients in the ASA arm (AUC: ASA 0.79; IBU 0.76).\n\nConclusion: IP-10 levels measured in DBS are associated with disease severity and treatment response and may serve as a biomarker for therapy monitoring and early prediction of microbiological outcomes in TB, irrespective of adjunctive host-directed therapies. These findings require validation in larger patient cohorts before the method can be implemented in clinical practice.", "abstract_shown": true, "affiliations": [ "Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway", "Institute of Clinical Medicine, University of Oslo, Oslo, Norway", "Experimental TB Unit, Germans Trias i Pujol Research Institute & Hospital (HUGTIP-IGTP), Badalona, Catalonia, Spain", "Laboratory of Structural Bioinformatics (GRIB), Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain", "Universitat Autònoma de Barcelona, Bellaterra, Catalonia, Spain", "Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain", "Perinatal HIV Research Unit (PHRU), University of the Witwatersrand, Johannesburg, South Africa", "School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa", "Centre for TB Research, Johns Hopkins University, Baltimore, MD, United States", "Microbiology Department, Northern Metropolitan Clinical Laboratory, Hospital Universitari Germans Trias I Pujol, Badalona, Catalonia, Spain" ], "article_type": "research article", "arxiv": null, "author_total": 15, "authors": [ { "affs": [ 0, 1 ], "name": "Iselin Høgbakk Edlund" }, { "affs": [ 0 ], "name": "Noelia Alonso-Rodriguez" }, { "affs": [ 2, 3 ], "name": "Chiara Sopegno" }, { "affs": [ 2 ], "name": "Judith Farrés" }, { "affs": [ 2, 4 ], "name": "Nino Gogichadze" }, { "affs": [ 2, 5 ], "name": "Lilibeth Arias" }, { "affs": [ 2, 5 ], "name": "Kaori L Fonseca" }, { "affs": [ 6, 7 ], "name": "Kennedy Otwombe" }, { "affs": [ 6 ], "name": "Ziyaad Waja" }, { "affs": [ 6 ], "name": "Tumelo Moloantoa" }, { "affs": [ 6 ], "name": "Natasha Pillay" }, { "affs": [ 6 ], "name": "Thabiso Seiphetlo" }, { "affs": [ 6, 8 ], "name": "Neil Martinson" }, { "affs": [ 2, 4, 5, 9 ], "name": "Cristina Vilaplana" }, { "affs": [ 0, 1 ], "name": "Anne Ma Dyrhol-Riise" } ], "bibtex": "https://research.draconitic.com/paper/e5gghzgrx2v1y.bib", "cited_by": 0, "doi": "10.3389/fimmu.2026.1924239", "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696322/", "id": "e5gghzgrx2v1y", "issns": [ "1664-3224" ], "landing_url": "https://doi.org/10.3389/fimmu.2026.1924239", "language": "en", "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Original Research" ], [ "openalex", "2725|Tuberculosis Research and Epidemiology" ] ], "openalex": "W7221441397", "pdf_url": "https://europepmc.org/articles/PMC13696322?pdf=render", "pmcid": "PMC13696322", "pmid": "42935866", "published": "2026-10-12", "publisher": "Frontiers Media SA", "ris": "https://research.draconitic.com/paper/e5gghzgrx2v1y.ris", "sources": [ { "first_seen": "2026-10-30T12:17:42Z", "native_id": "PMC13696322", "source": "pmc", "url": "https://doi.org/10.3389/fimmu.2026.1924239" }, { "first_seen": "2026-10-30T12:19:15Z", "native_id": "10.3389/fimmu.2026.1924239", "source": "crossref", "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1924239/full" }, { "first_seen": "2026-10-30T12:22:24Z", "native_id": "MED:42935866", "source": "europepmc", "url": "https://europepmc.org/article/MED/42935866" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2725|Tuberculosis Research and Epidemiology", "subfield": "infectious-disease" } ], "title": "Dried blood spot IP-10 as a biomarker of tuberculosis severity and treatment responses: results from a phase IIb trial of adjunctive acetylsalicylic acid and ibuprofen", "title_text": "Dried blood spot IP-10 as a biomarker of tuberculosis severity and treatment responses: results from a phase IIb trial of adjunctive acetylsalicylic acid and ibuprofen", "type": "peer-reviewed", "updated_at": "2026-10-30T12:33:41Z", "url": "https://research.draconitic.com/paper/e5gghzgrx2v1y", "venue": "Frontiers in Immunology", "versions": [] }