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LPS-binding protein and IL-6 mark paradoxical tuberculosis immune reconstitution inflammatory syndrome in HIV patients

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dc.contributor.author Goovaerts, O. en_US
dc.contributor.author Jennes, W. en_US
dc.contributor.author Massinga-Loembe, M. en_US
dc.contributor.author Ceulemans, A. en_US
dc.contributor.author Worodria, W. en_US
dc.contributor.author Mayanja-Kizza, H. en_US
dc.contributor.author Colebunders, R. en_US
dc.contributor.author Kestens, L. en_US
dc.date.accessioned 2014-09-25T13:39:16Z
dc.date.available 2014-09-25T13:39:16Z
dc.date.issued 2013 en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0081856 en_US
dc.identifier.other ITG-B1A; ITG-B2B; ITG-B3B; ITG-B4B; ITG-C7A; ITG-BLA; MULTI; DBM; U-IMMUN; DCS; U-HIVCLI; JIF; DOI; FTA; E-only; UPD56 en_US
dc.identifier.uri http://hdl.handle.net/10390/7545
dc.description.abstract 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. en_US
dc.language English en_US
dc.subject Viral diseases en_US
dc.subject HIV en_US
dc.subject AIDS en_US
dc.subject Co-infections en_US
dc.subject Bacterial diseases en_US
dc.subject Tuberculosis en_US
dc.subject Mycobacterium tuberculosis en_US
dc.subject Immune reconstitution inflammatory syndrome (IRIS) en_US
dc.subject IRIS en_US
dc.subject HAART en_US
dc.subject Antiretrovirals en_US
dc.subject Cytokines en_US
dc.subject Biomarkers en_US
dc.subject Polysaccharides en_US
dc.subject Proteins en_US
dc.subject IL-6 en_US
dc.subject GCSF en_US
dc.subject LBP en_US
dc.subject IL-4 en_US
dc.subject IL-7 en_US
dc.subject IL-8 en_US
dc.subject G-CSF en_US
dc.subject I-FABP en_US
dc.subject Uganda en_US
dc.subject Africa, East en_US
dc.title LPS-binding protein and IL-6 mark paradoxical tuberculosis immune reconstitution inflammatory syndrome in HIV patients en_US
dc.type Article-E en_US
dc.citation.issue 11 en_US
dc.citation.jtitle PLoS ONE en_US
dc.citation.volume 8 en_US
dc.citation.pages e81856 en_US
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/24312369 en_US
dc.citation.jabbreviation PLoS ONE en_US


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