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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
LPS-binding protein and IL-6 Mark paradoxical tuberculosis immune reconstitution inflammatory syndrome in HIV patients
PLoS ONE, Volume 8, No. 11, Article e81856, Year 2013
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Description
Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB co-infected patients initiating antiretroviral therapy (ART). The role of the innate immune system in TB-IRIS is becoming increasingly apparent, however the potential involvement in TB-IRIS of a leaky gut and proteins that interfere with TLR stimulation by binding PAMPs has not been investigated before. Here we aimed to investigate the innate nature of the cytokine response in TB-IRIS and to identify novel potential biomarkers. Methods: From a large prospective cohort of HIV-TB co-infected patients receiving TB treatment, we compared 40 patients who developed TB-IRIS during the first month of ART with 40 patients matched for age, sex and baseline CD4 count who did not. We analyzed plasma levels of lipopolysaccharide (LPS)-binding protein (LBP), LPS, sCD14, endotoxin-core antibody, intestinal fatty acid-binding protein (I-FABP) and 18 pro-and anti-inflammatory cytokines before and during ART. Results: We observed lower baseline levels of IL-6 (p = 0.041), GCSF (p = 0.036) and LBP (p = 0.016) in TB-IRIS patients. At IRIS event, we detected higher levels of LBP, IL-1RA, IL-4, IL-6, IL-7, IL-8, G-CSF (p ≤ 0.032) and lower I-FABP levels (p = 0.013) compared to HIV-TB co-infected controls. Only IL-6 showed an independent effect in multivariate models containing significant cytokines from pre-ART (p = 0.039) and during TB-IRIS (p = 0.034). Conclusion: We report pre-ART IL-6 and LBP levels as well as IL-6, LBP and I-FABP levels during IRIS-event as potential biomarkers in TB-IRIS. Our results show no evidence of the possible contribution of a leaky gut to TB-IRIS and indicate that IL-6 holds a distinct role in the disturbed innate cytokine profile before and during TB-IRIS. Future clinical studies should investigate the importance and clinical relevance of these markers for the diagnosis and treatment of TB-IRIS. Copyright: © 2013 Goovaerts et al.
Authors & Co-Authors
Goovaerts, Odin
Belgium, Antwerpen
Prins Leopold Instituut Voor Tropische Geneeskunde
Belgium, Antwerpen
Universiteit Antwerpen
Jennes, Wim
Belgium, Antwerpen
Prins Leopold Instituut Voor Tropische Geneeskunde
Massinga-Loembé, Marguérite
Belgium, Antwerpen
Prins Leopold Instituut Voor Tropische Geneeskunde
Gabon, Lambarene
Unité de Recherche Médicale, Albert Schweitzer Hospital
Germany, Tubingen
Eberhard Karls Universität Tübingen
Ceulemans, Ann
Belgium, Antwerpen
Prins Leopold Instituut Voor Tropische Geneeskunde
Worodria, William O.
Uganda, Kampala
Mulago Hospital
Uganda, Kampala
Makerere University College of Health Sciences
Uganda, Kampala
Infectious Diseases Network for Treatment and Research in Africa Interact
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Mayanja-Kizza, Harriet
Uganda, Kampala
Mulago Hospital
Uganda, Kampala
Makerere University College of Health Sciences
Uganda, Centre
Joint Clinical Research
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Colebunders, Robert Leon
Belgium, Antwerpen
Prins Leopold Instituut Voor Tropische Geneeskunde
Belgium, Antwerpen
Universiteit Antwerpen
Kestens, Luc L.
Belgium, Antwerpen
Prins Leopold Instituut Voor Tropische Geneeskunde
Belgium, Antwerpen
Universiteit Antwerpen
Mascart, Françoise
Belgium, Brussels
Université Libre de Bruxelles
Van den Bergh, Rafael
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Belgium, Brussels
Vrije Universiteit Brussel
Locht, Camille
France, Lille
Institut Pasteur de Lille
Reiss, Peter
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Cobelens, Frank G.J.
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Ondoa, Pascale
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Pakker, Nadine G.
Uganda, Kampala
Infectious Diseases Network for Treatment and Research in Africa Interact
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Mugerwa, Roy D.
Uganda, Kampala
Infectious Diseases Network for Treatment and Research in Africa Interact
Statistics
Citations: 46
Authors: 16
Affiliations: 13
Identifiers
Doi:
10.1371/journal.pone.0081856
e-ISSN:
19326203
Research Areas
Infectious Diseases
Study Design
Cohort Study