C1q and HBHA-specific IL-13 levels as surrogate plasma biomarkers for monitoring tuberculosis treatment efficacy: a cross-sectional cohort study in Paraguay

IntroductionNew diagnostic tools are needed to rapidly assess the efficacy of pulmonary tuberculosis (PTB) treatment. The aim of this study was to evaluate several immune biomarkers in an observational and cross-sectional cohort study conducted in Paraguay.MethodsThirty-two patients with clinically...

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Main Authors: Graciela Russomando, Diana Sanabria, Chyntia Carolina Díaz Acosta, Leticia Rojas, Laura Franco, Rossana Arenas, Giovanni Delogu, Mame Diarra Bousso Ndiaye, Rim Bayaa, Niaina Rakotosamimanana, Delia Goletti, Jonathan Hoffmann
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-03-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1308015/full
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author Graciela Russomando
Diana Sanabria
Chyntia Carolina Díaz Acosta
Leticia Rojas
Laura Franco
Rossana Arenas
Giovanni Delogu
Mame Diarra Bousso Ndiaye
Rim Bayaa
Niaina Rakotosamimanana
Delia Goletti
Jonathan Hoffmann
author_facet Graciela Russomando
Diana Sanabria
Chyntia Carolina Díaz Acosta
Leticia Rojas
Laura Franco
Rossana Arenas
Giovanni Delogu
Mame Diarra Bousso Ndiaye
Rim Bayaa
Niaina Rakotosamimanana
Delia Goletti
Jonathan Hoffmann
author_sort Graciela Russomando
collection DOAJ
description IntroductionNew diagnostic tools are needed to rapidly assess the efficacy of pulmonary tuberculosis (PTB) treatment. The aim of this study was to evaluate several immune biomarkers in an observational and cross-sectional cohort study conducted in Paraguay.MethodsThirty-two patients with clinically and microbiologically confirmed PTB were evaluated before starting treatment (T0), after 2 months of treatment (T1) and at the end of treatment (T2). At each timepoint plasma levels of IFN-y, 17 pro- and anti-inflammatory cytokines/chemokines and complement factors C1q, C3 and C4 were assessed in unstimulated and Mtb-specific stimulated whole blood samples using QuantiFERON-TB gold plus and recombinant Mycobacterium smegmatis heparin binding hemagglutinin (rmsHBHA) as stimulation antigen. Complete blood counts and liver enzyme assays were also evaluated and correlated with biomarker levels in plasma.ResultsIn unstimulated plasma, C1q (P<0.001), C4 (P<0.001), hemoglobin (P<0.001), lymphocyte proportion (P<0.001) and absolute white blood cell count (P=0.01) were significantly higher in PTB patients at baseline than in cured patients. C1q and C4 levels were found to be related to Mycobacterium tuberculosis load in sputum. Finally, a combinatorial analysis identified a plasma host signature comprising the detection of C1q and IL-13 levels in response to rmsHBHA as a tool differentiating PTB patients from cured TB profiles, with an AUC of 0.92 (sensitivity 94% and specificity 79%).ConclusionThis observational study provides new insights on host immune responses throughout anti-TB treatment and emphasizes the role of host C1q and HBHA-specific IL-13 response as surrogate plasma biomarkers for monitoring TB treatment efficacy.
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spelling doaj.art-6c93c45ab72847128dd39b3f9657c49c2024-03-13T14:09:06ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13080151308015C1q and HBHA-specific IL-13 levels as surrogate plasma biomarkers for monitoring tuberculosis treatment efficacy: a cross-sectional cohort study in ParaguayGraciela Russomando0Diana Sanabria1Chyntia Carolina Díaz Acosta2Leticia Rojas3Laura Franco4Rossana Arenas5Giovanni Delogu6Mame Diarra Bousso Ndiaye7Rim Bayaa8Niaina Rakotosamimanana9Delia Goletti10Jonathan Hoffmann11Instituto de Investigaciones en Ciencias de la Salud, National University of Asunción, Asunción, ParaguayInstituto de Investigaciones en Ciencias de la Salud, National University of Asunción, Asunción, ParaguayInstituto de Investigaciones en Ciencias de la Salud, National University of Asunción, Asunción, ParaguayInstituto de Investigaciones en Ciencias de la Salud, National University of Asunción, Asunción, ParaguayInstituto de Investigaciones en Ciencias de la Salud, National University of Asunción, Asunción, ParaguayHospital General de San Lorenzo, Ministerio de Salud Pública y Bienestar Social (MSPyBS), Asunción, ParaguayDipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie – Sezione di Microbiologia, Università Cattolica del Sacro Cuore, Rome, ItalyUnité des Mycobactéries, Institut Pasteur de Madagascar, Antananarivo, MadagascarMedical and Scientific Department, Fondation Mérieux, Lyon, FranceUnité des Mycobactéries, Institut Pasteur de Madagascar, Antananarivo, MadagascarTranslational Research Unit, Department of Epidemiology and Preclinical Research, “L. Spallanzani” National Institute for Infectious Diseases (INMI), IRCCS, Rome, ItalyMedical and Scientific Department, Fondation Mérieux, Lyon, FranceIntroductionNew diagnostic tools are needed to rapidly assess the efficacy of pulmonary tuberculosis (PTB) treatment. The aim of this study was to evaluate several immune biomarkers in an observational and cross-sectional cohort study conducted in Paraguay.MethodsThirty-two patients with clinically and microbiologically confirmed PTB were evaluated before starting treatment (T0), after 2 months of treatment (T1) and at the end of treatment (T2). At each timepoint plasma levels of IFN-y, 17 pro- and anti-inflammatory cytokines/chemokines and complement factors C1q, C3 and C4 were assessed in unstimulated and Mtb-specific stimulated whole blood samples using QuantiFERON-TB gold plus and recombinant Mycobacterium smegmatis heparin binding hemagglutinin (rmsHBHA) as stimulation antigen. Complete blood counts and liver enzyme assays were also evaluated and correlated with biomarker levels in plasma.ResultsIn unstimulated plasma, C1q (P<0.001), C4 (P<0.001), hemoglobin (P<0.001), lymphocyte proportion (P<0.001) and absolute white blood cell count (P=0.01) were significantly higher in PTB patients at baseline than in cured patients. C1q and C4 levels were found to be related to Mycobacterium tuberculosis load in sputum. Finally, a combinatorial analysis identified a plasma host signature comprising the detection of C1q and IL-13 levels in response to rmsHBHA as a tool differentiating PTB patients from cured TB profiles, with an AUC of 0.92 (sensitivity 94% and specificity 79%).ConclusionThis observational study provides new insights on host immune responses throughout anti-TB treatment and emphasizes the role of host C1q and HBHA-specific IL-13 response as surrogate plasma biomarkers for monitoring TB treatment efficacy.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1308015/fullpulmonary tuberculosishost biomarkerstreatment immunomonitoringplasma protein signatureimmunodiagnostic
spellingShingle Graciela Russomando
Diana Sanabria
Chyntia Carolina Díaz Acosta
Leticia Rojas
Laura Franco
Rossana Arenas
Giovanni Delogu
Mame Diarra Bousso Ndiaye
Rim Bayaa
Niaina Rakotosamimanana
Delia Goletti
Jonathan Hoffmann
C1q and HBHA-specific IL-13 levels as surrogate plasma biomarkers for monitoring tuberculosis treatment efficacy: a cross-sectional cohort study in Paraguay
Frontiers in Immunology
pulmonary tuberculosis
host biomarkers
treatment immunomonitoring
plasma protein signature
immunodiagnostic
title C1q and HBHA-specific IL-13 levels as surrogate plasma biomarkers for monitoring tuberculosis treatment efficacy: a cross-sectional cohort study in Paraguay
title_full C1q and HBHA-specific IL-13 levels as surrogate plasma biomarkers for monitoring tuberculosis treatment efficacy: a cross-sectional cohort study in Paraguay
title_fullStr C1q and HBHA-specific IL-13 levels as surrogate plasma biomarkers for monitoring tuberculosis treatment efficacy: a cross-sectional cohort study in Paraguay
title_full_unstemmed C1q and HBHA-specific IL-13 levels as surrogate plasma biomarkers for monitoring tuberculosis treatment efficacy: a cross-sectional cohort study in Paraguay
title_short C1q and HBHA-specific IL-13 levels as surrogate plasma biomarkers for monitoring tuberculosis treatment efficacy: a cross-sectional cohort study in Paraguay
title_sort c1q and hbha specific il 13 levels as surrogate plasma biomarkers for monitoring tuberculosis treatment efficacy a cross sectional cohort study in paraguay
topic pulmonary tuberculosis
host biomarkers
treatment immunomonitoring
plasma protein signature
immunodiagnostic
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1308015/full
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