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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| Veröffentlicht in: | PLoS neglected tropical diseases 2018-08, Vol.12 (8), p.e0006710-e0006710 |
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| description | 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. |
| doi_str_mv | 10.1371/journal.pntd.0006710 |
| format | Article |
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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.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0006710</identifier><identifier>PMID: 30089120</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PLoS neglected tropical diseases, 2018-08, Vol.12 (8), p.e0006710-e0006710</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Goovaerts et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Goovaerts et al 2018 Goovaerts et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c624t-3c4cb424dd11b1bf008b4bee845cb2fff8d2e0ed710b66c0bac2612628ef56733</citedby><cites>FETCH-LOGICAL-c624t-3c4cb424dd11b1bf008b4bee845cb2fff8d2e0ed710b66c0bac2612628ef56733</cites><orcidid>0000-0002-4959-4677</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101407/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101407/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2104,2930,23873,27931,27932,53798,53800</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30089120$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Downs, Jennifer A.</contributor><creatorcontrib>Goovaerts, Odin</creatorcontrib><creatorcontrib>Mwinzi, Pauline N M</creatorcontrib><creatorcontrib>Muok, Erick M O</creatorcontrib><creatorcontrib>Ceulemans, Ann</creatorcontrib><creatorcontrib>Colebunders, Robert</creatorcontrib><creatorcontrib>Kestens, Luc</creatorcontrib><title>Aberrant plasma MMP and TIMP dynamics in Schistosoma - Immune reconstitution inflammatory syndrome (IRIS)</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>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.</description><subject>Adult</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Antiretroviral drugs</subject><subject>Antiretroviral therapy</subject><subject>Biological markers</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>C-reactive protein</subject><subject>Care and treatment</subject><subject>Case-Control Studies</subject><subject>Cohort Studies</subject><subject>Cohorts</subject><subject>Coinfection</subject><subject>Cytokines</subject><subject>Development and progression</subject><subject>Drug therapy</subject><subject>Dynamics</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>HIV</subject><subject>HIV Infections</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Identification and classification</subject><subject>Immune reconstitution</subject><subject>Immune Reconstitution Inflammatory Syndrome - diagnosis</subject><subject>Immune Reconstitution Inflammatory Syndrome - etiology</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Interstitial collagenase</subject><subject>Intestine</subject><subject>Kenya - epidemiology</subject><subject>Levels</subject><subject>Male</subject><subject>Matrilysin</subject><subject>Matrix metalloproteinase</subject><subject>Matrix metalloproteinases</subject><subject>Matrix Metalloproteinases - blood</subject><subject>Matrix Metalloproteinases - metabolism</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Pathogens</subject><subject>Plasma levels</subject><subject>Proteases</subject><subject>Proteins</subject><subject>Schistosoma mansoni</subject><subject>Schistosomiasis</subject><subject>Schistosomiasis mansoni - complications</subject><subject>Schistosomiasis mansoni - epidemiology</subject><subject>Schistosomiasis mansoni - immunology</subject><subject>Signs and symptoms</subject><subject>Stromelysin 2</subject><subject>Symptoms</subject><subject>Tissue</subject><subject>Tissue inhibitor of metalloproteinase 1</subject><subject>Tissue inhibitor of metalloproteinase 2</subject><subject>Tissue Inhibitor of Metalloproteinases - blood</subject><subject>Tissue Inhibitor of Metalloproteinases - metabolism</subject><subject>Tropical diseases</subject><subject>Tuberculosis</subject><issn>1935-2735</issn><issn>1935-2727</issn><issn>1935-2735</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNptkltrFDEUxwdRbK1-A9EBQerDrrlNJvsiLMXLQIti63PIbXZTMsk2yQj77c12p2VXSh4STn7nf65V9RaCOcQt_HwbxuiFm2981nMAAG0heFadwgVuZqjFzfOD90n1KqVbAJpFw-DL6gQDwBYQgdPKLqWJUfhcb5xIg6ivrn7Vwuv6pisPvfVisCrV1tfXam1TDikUaFZ3wzB6U0ejgk_Z5jHb4AvWOzEMIoe4rdPW6xgGU593v7vrT6-rF71wybyZ7rPqz7evNxc_Zpc_v3cXy8uZoojkGVZESYKI1hBKKPuSqSTSGEYaJVHf90wjA4wu1UpKFZBCIQoRRcz0DW0xPqve73U3LiQ-dSlxhBqEFoSQHdHtCR3ELd9EO4i45UFYfm8IccVFzFY5w6GipoWQYqRLSkRKzCBjwsC-BY2UtGh9maKNcjBaGZ-jcEeixz_ervkq_OUUAkhAWwTOJ4EY7kaTMh9sUsY54U0YS96AUdSwFu9iffgPfbq6iVqJUkCZSChx1U6UL5umZawFC1Co-RNUOdqUgQdvelvsRw4fDxzWRri8TsHdzz0dg2QPqhhSiqZ_bAYEfLe5D1nz3ebyaXOL27vDRj46Pawq_gcuS-oF</recordid><startdate>20180801</startdate><enddate>20180801</enddate><creator>Goovaerts, Odin</creator><creator>Mwinzi, Pauline N M</creator><creator>Muok, Erick M O</creator><creator>Ceulemans, Ann</creator><creator>Colebunders, Robert</creator><creator>Kestens, Luc</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7SS</scope><scope>7T2</scope><scope>7T7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>H95</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-4959-4677</orcidid></search><sort><creationdate>20180801</creationdate><title>Aberrant plasma MMP and TIMP dynamics in Schistosoma - Immune reconstitution inflammatory syndrome (IRIS)</title><author>Goovaerts, Odin ; Mwinzi, Pauline N M ; Muok, Erick M O ; Ceulemans, Ann ; Colebunders, Robert ; Kestens, Luc</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c624t-3c4cb424dd11b1bf008b4bee845cb2fff8d2e0ed710b66c0bac2612628ef56733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antigens</topic><topic>Antiretroviral drugs</topic><topic>Antiretroviral therapy</topic><topic>Biological markers</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers</topic><topic>C-reactive protein</topic><topic>Care and treatment</topic><topic>Case-Control Studies</topic><topic>Cohort Studies</topic><topic>Cohorts</topic><topic>Coinfection</topic><topic>Cytokines</topic><topic>Development and progression</topic><topic>Drug therapy</topic><topic>Dynamics</topic><topic>Female</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>HIV</topic><topic>HIV Infections</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Identification and classification</topic><topic>Immune reconstitution</topic><topic>Immune Reconstitution Inflammatory Syndrome - diagnosis</topic><topic>Immune Reconstitution Inflammatory Syndrome - etiology</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Infections</topic><topic>Inflammation</topic><topic>Interstitial collagenase</topic><topic>Intestine</topic><topic>Kenya - epidemiology</topic><topic>Levels</topic><topic>Male</topic><topic>Matrilysin</topic><topic>Matrix metalloproteinase</topic><topic>Matrix metalloproteinases</topic><topic>Matrix Metalloproteinases - blood</topic><topic>Matrix Metalloproteinases - metabolism</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Pathogens</topic><topic>Plasma levels</topic><topic>Proteases</topic><topic>Proteins</topic><topic>Schistosoma mansoni</topic><topic>Schistosomiasis</topic><topic>Schistosomiasis mansoni - complications</topic><topic>Schistosomiasis mansoni - epidemiology</topic><topic>Schistosomiasis mansoni - immunology</topic><topic>Signs and symptoms</topic><topic>Stromelysin 2</topic><topic>Symptoms</topic><topic>Tissue</topic><topic>Tissue inhibitor of metalloproteinase 1</topic><topic>Tissue inhibitor of metalloproteinase 2</topic><topic>Tissue Inhibitor of Metalloproteinases - blood</topic><topic>Tissue Inhibitor of Metalloproteinases - metabolism</topic><topic>Tropical diseases</topic><topic>Tuberculosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Goovaerts, Odin</creatorcontrib><creatorcontrib>Mwinzi, Pauline N M</creatorcontrib><creatorcontrib>Muok, Erick M O</creatorcontrib><creatorcontrib>Ceulemans, Ann</creatorcontrib><creatorcontrib>Colebunders, Robert</creatorcontrib><creatorcontrib>Kestens, Luc</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS neglected tropical diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Goovaerts, Odin</au><au>Mwinzi, Pauline N M</au><au>Muok, Erick M O</au><au>Ceulemans, Ann</au><au>Colebunders, Robert</au><au>Kestens, Luc</au><au>Downs, Jennifer A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aberrant plasma MMP and TIMP dynamics in Schistosoma - Immune reconstitution inflammatory syndrome (IRIS)</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2018-08-01</date><risdate>2018</risdate><volume>12</volume><issue>8</issue><spage>e0006710</spage><epage>e0006710</epage><pages>e0006710-e0006710</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30089120</pmid><doi>10.1371/journal.pntd.0006710</doi><orcidid>https://orcid.org/0000-0002-4959-4677</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1935-2735 |
| ispartof | PLoS neglected tropical diseases, 2018-08, Vol.12 (8), p.e0006710-e0006710 |
| issn | 1935-2735 1935-2727 1935-2735 |
| language | eng |
| recordid | cdi_plos_journals_2252294443 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; PubMed Central Open Access; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| 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 |
| title | Aberrant plasma MMP and TIMP dynamics in Schistosoma - Immune reconstitution inflammatory syndrome (IRIS) |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-03T21%3A24%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Aberrant%20plasma%20MMP%20and%20TIMP%20dynamics%20in%20Schistosoma%20-%20Immune%20reconstitution%20inflammatory%20syndrome%20(IRIS)&rft.jtitle=PLoS%20neglected%20tropical%20diseases&rft.au=Goovaerts,%20Odin&rft.date=2018-08-01&rft.volume=12&rft.issue=8&rft.spage=e0006710&rft.epage=e0006710&rft.pages=e0006710-e0006710&rft.issn=1935-2735&rft.eissn=1935-2735&rft_id=info:doi/10.1371/journal.pntd.0006710&rft_dat=%3Cgale_plos_%3EA557887090%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2252294443&rft_id=info:pmid/30089120&rft_galeid=A557887090&rft_doaj_id=oai_doaj_org_article_1c6e711632d24d4bb38188ae1f705bb6&rfr_iscdi=true |