Aberrant plasma MMP and TIMP dynamics in Schistosoma - Immune reconstitution inflammatory syndrome (IRIS)

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...

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Published in:	PLoS neglected tropical diseases 2018-08, Vol.12 (8), p.e0006710-e0006710
Main Authors:	Goovaerts, Odin, Mwinzi, Pauline N M, Muok, Erick M O, Ceulemans, Ann, Colebunders, Robert, Kestens, Luc
Format:	Article
Language:	eng
Subjects:	Adult Animals Antibodies Antigens Antiretroviral drugs Antiretroviral therapy Biological markers Biology and Life Sciences Biomarkers C-reactive protein Care and treatment Case-Control Studies Cohort Studies Cohorts Coinfection Cytokines Development and progression Drug therapy Dynamics Female Genetic aspects Health aspects HIV HIV Infections Human immunodeficiency virus Humans Identification and classification Immune reconstitution Immune Reconstitution Inflammatory Syndrome - diagnosis Immune Reconstitution Inflammatory Syndrome - etiology Immune response Immune system Infections Inflammation Interstitial collagenase Intestine Kenya - epidemiology Levels Male Matrilysin Matrix metalloproteinase Matrix metalloproteinases Matrix Metalloproteinases - blood Matrix Metalloproteinases - metabolism Medical research Medicine and Health Sciences Pathogens Plasma levels Proteases Proteins Schistosoma mansoni Schistosomiasis Schistosomiasis mansoni - complications Schistosomiasis mansoni - epidemiology Schistosomiasis mansoni - immunology Signs and symptoms Stromelysin 2 Symptoms Tissue Tissue inhibitor of metalloproteinase 1 Tissue inhibitor of metalloproteinase 2 Tissue Inhibitor of Metalloproteinases - blood Tissue Inhibitor of Metalloproteinases - metabolism Tropical diseases Tuberculosis
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Summary:	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. 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. 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). 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.
ISSN:	1935-2735 1935-2727 1935-2735