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
10 affiliations
- 1Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway
- 2Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- 3Experimental TB Unit, Germans Trias i Pujol Research Institute & Hospital (HUGTIP-IGTP), Badalona, Catalonia, Spain
- 4Laboratory of Structural Bioinformatics (GRIB), Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain
- 5Universitat Autònoma de Barcelona, Bellaterra, Catalonia, Spain
- 6Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
- 7Perinatal HIV Research Unit (PHRU), University of the Witwatersrand, Johannesburg, South Africa
- 8School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- 9Centre for TB Research, Johns Hopkins University, Baltimore, MD, United States
- 10Microbiology Department, Northern Metropolitan Clinical Laboratory, Hospital Universitari Germans Trias I Pujol, Badalona, Catalonia, Spain
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.
Methods: 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.
Results: 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).
Conclusion: 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.
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BibTeX
@article{edlund2026dried,
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}},
author = {Iselin Høgbakk Edlund and Noelia Alonso-Rodriguez and Chiara Sopegno and Judith Farrés and Nino Gogichadze and Lilibeth Arias and Kaori L Fonseca and Kennedy Otwombe and Ziyaad Waja and Tumelo Moloantoa and Natasha Pillay and Thabiso Seiphetlo and Neil Martinson and Cristina Vilaplana and Anne Ma Dyrhol-Riise},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1924239},
url = {https://doi.org/10.3389/fimmu.2026.1924239},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Iselin Høgbakk Edlund
AU - Noelia Alonso-Rodriguez
AU - Chiara Sopegno
AU - Judith Farrés
AU - Nino Gogichadze
AU - Lilibeth Arias
AU - Kaori L Fonseca
AU - Kennedy Otwombe
AU - Ziyaad Waja
AU - Tumelo Moloantoa
AU - Natasha Pillay
AU - Thabiso Seiphetlo
AU - Neil Martinson
AU - Cristina Vilaplana
AU - Anne Ma Dyrhol-Riise
PY - 2026
DA - 2026/10/12
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1924239
UR - https://doi.org/10.3389/fimmu.2026.1924239
AB - 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. Methods: 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. Results: 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). Conclusion: 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.
SN - 1664-3224
ER -