A set of plasmatic microRNA related to innate immune response highly predicts the onset of immune reconstitution inflammatory syndrome in tuberculosis co-infected HIV individuals (ANRS-12358 study)

BackgroundAfter initiation of combination antiretroviral treatment (cART), HIV-1/tuberculosis coinfected patients are at high risk of developing tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS). MicroRNAs, small molecules of approximately 22 nucleotides, which regulate p...

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Main Authors: Polidy Pean, Ratana Meng, Eliott Benichou, Pichsivannary Srey, Bunnet Dim, Laurence Borand, Olivier Marcy, Didier Laureillard, François-Xavier Blanc, Tineke Cantaert, Yoann Madec, Laurence Weiss, Daniel Scott-Algara
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Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1603338/full
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author Polidy Pean
Ratana Meng
Eliott Benichou
Eliott Benichou
Pichsivannary Srey
Bunnet Dim
Laurence Borand
Laurence Borand
Olivier Marcy
Didier Laureillard
François-Xavier Blanc
Tineke Cantaert
Yoann Madec
Laurence Weiss
Daniel Scott-Algara
author_facet Polidy Pean
Ratana Meng
Eliott Benichou
Eliott Benichou
Pichsivannary Srey
Bunnet Dim
Laurence Borand
Laurence Borand
Olivier Marcy
Didier Laureillard
François-Xavier Blanc
Tineke Cantaert
Yoann Madec
Laurence Weiss
Daniel Scott-Algara
author_sort Polidy Pean
collection DOAJ
description BackgroundAfter initiation of combination antiretroviral treatment (cART), HIV-1/tuberculosis coinfected patients are at high risk of developing tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS). MicroRNAs, small molecules of approximately 22 nucleotides, which regulate post-transcriptional gene expression and their profile has been proposed as a biomarker for many diseases. We tested whether the microRNA profile could be a predictive biomarker for TB-IRIS.MethodsTwenty-six selected microRNAs involved in the regulation of the innate immune response were investigated. Free plasmatic and microRNA-derived exosomes were measured by flow cytometry. The plasma from 74 HIV-1+TB+ individuals (35 IRIS and 39 non-IRIS) at the time of the diagnosis and before any treatment (baseline) of CAMELIA trial (ANRS1295-CIPRA KH001-DAIDS-ES ID10425); 15 HIV+TB− and 23 HIV−TB+, both naïve of any treatment; and 20 HIV−TB− individuals as controls were analysed.ResultsAt baseline, both IRIS and non-IRIS HIV+/TB+ individuals had similar demographic and clinical characteristics, including sex, age, body mass index, very low CD4+ cell counts (27 cells/mm3), and plasma HIV RNA load levels (5.76 log copies/ml). Twenty out of 26 plasmatic-microRNAs tested were no different between IRIS and controls. Twelve of the 26 tested microRNAs showed statistically significant differences between IRIS and non-IRIS patients (p-values ranging from p <0.05 to p <0.0001). Among these, five could discriminate between IRIS and non-IRIS individuals using ROC curve analysis (AUC scores ranging from 0.74 to 0.92). The combination of two (hsa-mir-29c-3p and hsa-mir-146a-5p) or three microRNAs (hsa-mir-29c-3p, hsa-mir-29a-3p, and hsa-mir-146a-5p) identified IRIS with 100% sensitivity and high specificity (95% and 97%, respectively).ConclusionThe combination of at least two or three plasmatic microRNAs known to regulate inflammation and/or cytokine responses could be used as biomarkers to discriminate IRIS from non-IRIS in HIV-TB co-infected individuals at the time of diagnosis and prior to any treatment.
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spelling doaj-art-838e31673f2c44d9986f02de9fa81fb02025-08-20T03:22:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.16033381603338A set of plasmatic microRNA related to innate immune response highly predicts the onset of immune reconstitution inflammatory syndrome in tuberculosis co-infected HIV individuals (ANRS-12358 study)Polidy Pean0Ratana Meng1Eliott Benichou2Eliott Benichou3Pichsivannary Srey4Bunnet Dim5Laurence Borand6Laurence Borand7Olivier Marcy8Didier Laureillard9François-Xavier Blanc10Tineke Cantaert11Yoann Madec12Laurence Weiss13Daniel Scott-Algara14Unité d’immunologie, Institut Pasteur du Cambodge, Phnom Penh, CambodiaUnité d’immunologie, Institut Pasteur du Cambodge, Phnom Penh, CambodiaUnité d’immunologie, Institut Pasteur du Cambodge, Phnom Penh, CambodiaUniversité Paris-Saclay, Gif-sur-Yvette, FranceInfectious Diseases Department, Sihanouk Hospital Center of HOPE, Phnom Penh, CambodiaClinical Research Group, Epidemiology and Public Health Unit, Institut Pasteur du Cambodge, Phom Penh, CambodiaClinical Research Group, Epidemiology and Public Health Unit, Institut Pasteur du Cambodge, Phom Penh, CambodiaCenter for Tuberculosis Research, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesResearch Institute for Sustainable Development (IRD) EMR 271, National Institute for Health and Medical Research (INSERM) UMR 1219, University of Bordeaux, Bordeaux, FranceInfectious and Tropical Diseases Department, University Hospital, Nimes, FranceNantes Université, CHU Nantes, Service de Pneumologie, l’institut du thorax, Nantes, FranceUnité d’immunologie, Institut Pasteur du Cambodge, Phnom Penh, CambodiaEpidemiology of Emerging Diseases, Institut Pasteur, Université de Paris, Paris, France0Université Paris Cité, Immunology, Paris, France1International Affairs Departement, Institut Pasteur, Paris, FranceBackgroundAfter initiation of combination antiretroviral treatment (cART), HIV-1/tuberculosis coinfected patients are at high risk of developing tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS). MicroRNAs, small molecules of approximately 22 nucleotides, which regulate post-transcriptional gene expression and their profile has been proposed as a biomarker for many diseases. We tested whether the microRNA profile could be a predictive biomarker for TB-IRIS.MethodsTwenty-six selected microRNAs involved in the regulation of the innate immune response were investigated. Free plasmatic and microRNA-derived exosomes were measured by flow cytometry. The plasma from 74 HIV-1+TB+ individuals (35 IRIS and 39 non-IRIS) at the time of the diagnosis and before any treatment (baseline) of CAMELIA trial (ANRS1295-CIPRA KH001-DAIDS-ES ID10425); 15 HIV+TB− and 23 HIV−TB+, both naïve of any treatment; and 20 HIV−TB− individuals as controls were analysed.ResultsAt baseline, both IRIS and non-IRIS HIV+/TB+ individuals had similar demographic and clinical characteristics, including sex, age, body mass index, very low CD4+ cell counts (27 cells/mm3), and plasma HIV RNA load levels (5.76 log copies/ml). Twenty out of 26 plasmatic-microRNAs tested were no different between IRIS and controls. Twelve of the 26 tested microRNAs showed statistically significant differences between IRIS and non-IRIS patients (p-values ranging from p <0.05 to p <0.0001). Among these, five could discriminate between IRIS and non-IRIS individuals using ROC curve analysis (AUC scores ranging from 0.74 to 0.92). The combination of two (hsa-mir-29c-3p and hsa-mir-146a-5p) or three microRNAs (hsa-mir-29c-3p, hsa-mir-29a-3p, and hsa-mir-146a-5p) identified IRIS with 100% sensitivity and high specificity (95% and 97%, respectively).ConclusionThe combination of at least two or three plasmatic microRNAs known to regulate inflammation and/or cytokine responses could be used as biomarkers to discriminate IRIS from non-IRIS in HIV-TB co-infected individuals at the time of diagnosis and prior to any treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1603338/fullmicroRNAexosomesHIVtuberculosisIRISbiomarkers
spellingShingle Polidy Pean
Ratana Meng
Eliott Benichou
Eliott Benichou
Pichsivannary Srey
Bunnet Dim
Laurence Borand
Laurence Borand
Olivier Marcy
Didier Laureillard
François-Xavier Blanc
Tineke Cantaert
Yoann Madec
Laurence Weiss
Daniel Scott-Algara
A set of plasmatic microRNA related to innate immune response highly predicts the onset of immune reconstitution inflammatory syndrome in tuberculosis co-infected HIV individuals (ANRS-12358 study)
Frontiers in Immunology
microRNA
exosomes
HIV
tuberculosis
IRIS
biomarkers
title A set of plasmatic microRNA related to innate immune response highly predicts the onset of immune reconstitution inflammatory syndrome in tuberculosis co-infected HIV individuals (ANRS-12358 study)
title_full A set of plasmatic microRNA related to innate immune response highly predicts the onset of immune reconstitution inflammatory syndrome in tuberculosis co-infected HIV individuals (ANRS-12358 study)
title_fullStr A set of plasmatic microRNA related to innate immune response highly predicts the onset of immune reconstitution inflammatory syndrome in tuberculosis co-infected HIV individuals (ANRS-12358 study)
title_full_unstemmed A set of plasmatic microRNA related to innate immune response highly predicts the onset of immune reconstitution inflammatory syndrome in tuberculosis co-infected HIV individuals (ANRS-12358 study)
title_short A set of plasmatic microRNA related to innate immune response highly predicts the onset of immune reconstitution inflammatory syndrome in tuberculosis co-infected HIV individuals (ANRS-12358 study)
title_sort set of plasmatic microrna related to innate immune response highly predicts the onset of immune reconstitution inflammatory syndrome in tuberculosis co infected hiv individuals anrs 12358 study
topic microRNA
exosomes
HIV
tuberculosis
IRIS
biomarkers
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1603338/full
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