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Title
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Aberrant plasma MMP and TIMP dynamics in Schistosoma : immune reconstitution inflammatory syndrome (IRIS)
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Author
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Abstract
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| Background Among the different faces of immune reconstitution inflammatory syndrome (IRIS) developing in HIV-patients, no clinical definition has been reported for Schistosomiasis-IRIS (Schisto-IRIS). Although Schisto-IRIS remains largely uninvestigated, matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) have previously been associated with S. mansoni infection and tuberculosis-IRIS. Here, we aimed to investigate the relevance of these markers in Schisto-IRIS. Methodology Patients were diagnosed with IRIS related to S. mansoni within a cohort of patients with Schistosomiasis-HIV co-infection, using a clinical working definition of Schisto-IRIS. We compared 9 patients who developed Schisto-IRIS to 9 Schisto(+)HIV(+) controls who did not, and 9 Schisto(-)HIV(+) controls. Plasma levels of MMP-1, MMP-7, MMP-10, TIMP-1, TIMP-2, sCD14, intestinal fatty-acid binding protein, C-reactive protein, and 8 anti-nuclear antibodies (ANA) were analyzed prior to and during 3 months of ART. Principal findings Although no differences were observed for MMP-1 and -7, MMP-10 levels decreased significantly in Schisto(+)HIV(+) controls during 3 months of ART (p = 0.005) while persisting in Schisto-IRIS patients at significantly higher levels compared to Schisto(-)HIV(+) controls (p <= 0.030). In contrast TIMP-1 levels only decreased significantly in Schisto-IRIS patients (p = 0.012), while TIMP-2 levels were lower compared to Schisto(+)HIV(+) controls at 2 weeks (p = 0.007), 1 month (p = 0.005) and 3 months (p = 0.031) of ART. Five out of 8 ANAs studied decreased significantly in Schisto-IRIS patients after 1 month of ART(p <= 0.039), whereas only 1 ANA decreased for Schisto(+)HIV(+) controls (p = 0.027). Conclusions/Significance In this study, we propose a working definition for the diagnosis of Schisto-IRIS in resource limited settings. We report persistent plasma levels of MMP-10, along with a more pronounced decrease in TIMP-1 and ANA-levels, and low levels of TIMP-2 during 3 months of ART. Corresponding to the clinical symptoms, these data suggest that Schisto-IRIS is marked by unbalanced MMP/TIMP dynamics which favor inflammation. |
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Language
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English
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Source (journal)
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PLoS neglected tropical diseases
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Publication
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2018
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ISSN
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1935-2727
1935-2735
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DOI
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10.1371/JOURNAL.PNTD.0006710
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Volume/pages
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12
:8
(2018)
, 23 p.
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Article Reference
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e0006710
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ISI
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000443381000045
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Pubmed ID
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30089120
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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