{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:36:03Z","timestamp":1789029363567,"version":"build-2803163510"},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"vor","delay-in-days":118,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/L006529"],"award-info":[{"award-number":["MR\/L006529"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000761","name":"Imperial College London","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000761","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp;amp; Trans Imm"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Cerebral malaria (CM) is a complication of <jats:italic>Plasmodium falciparum<\/jats:italic> malaria, in which progressive brain swelling is associated with sequestration of parasites and impaired barrier function of the cerebral microvascular endothelium. To test the hypothesis that localised release of matrix metallopeptidase 8 (MMP8) within the retina is implicated in microvascular leak in CM, we examined its expression and association with extravascular fibrinogen leak in a case\u2013control study of post\u2010mortem retinal samples from 13 Malawian children who met the clinical case definition of CM during life. Cases were seven children who were found on post\u2010mortem examination to have \u2018true\u2010CM\u2019 (parasite sequestration in brain blood vessels), whilst controls were six children who had alternative causes of death (\u2018faux\u2010CM\u2019, no parasite sequestration in blood vessels).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used immunofluorescence microscopy and independent scoring, by two assessors blinded to the CM status, to assess MMP8 expression, extravascular fibrinogen as an indicator of vascular leak and their co\u2010localisation in the retinal microvasculature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In \u2018true\u2010CM\u2019 subjects, MMP8 staining was invariably associated with sequestered parasites and a median of 88% (IQR\u00a0=\u00a074\u201391%) of capillaries showed MMP8 staining, compared with 14% (IQR\u00a0=\u00a03.8\u201324%) in \u2018faux\u2010CM\u2019 (<jats:italic>P<\/jats:italic>\u2010value\u00a0=\u00a00.001). 41% (IQR\u00a0=\u00a028\u201349%) of capillaries in \u2018true\u2010CM\u2019 subjects showed co\u2010localisation of extravascular fibrinogen leak and MMP8 staining, compared with 1.8% of capillaries in \u2018faux\u2010CM\u2019 (IQR\u00a0=\u00a00\u20133.9%, <jats:italic>P<\/jats:italic>\u2010value\u00a0=\u00a00.01). Vascular leak was rare in the absence of MMP8 staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Matrix metallopeptidase 8 was extensively expressed in retinal capillaries of Malawian children with malarial retinopathy and strongly associated with vascular leak. Our findings implicate MMP8 as a cause of the vascular endothelial barrier disruption in CM, which may precipitate fatal brain swelling.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1263","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T12:27:25Z","timestamp":1619699245000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Localised release of matrix metallopeptidase 8 in fatal cerebral malaria"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0440-9335","authenticated-orcid":false,"given":"Athina","family":"Georgiadou","sequence":"first","affiliation":[{"name":"Department of Infectious Disease Section of Paediatric Infectious Disease Imperial College London  London UK"},{"name":"Centre for Paediatrics and Child Health Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveena","family":"Naidu","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Section of Paediatric Infectious Disease Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Walsh","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Section of Paediatric Infectious Disease Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Kamiza","sequence":"additional","affiliation":[{"name":"Department of Pathology College of Medicine University of Malawi  Blantyre Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Barrera","sequence":"additional","affiliation":[{"name":"Department of Eye and Vision Science Institute of Life Course and Medical Sciences Liverpool University Hospitals Foundation Trust Members of Liverpool Health Partners University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon P","family":"Harding","sequence":"additional","affiliation":[{"name":"Department of Eye and Vision Science Institute of Life Course and Medical Sciences Liverpool University Hospitals Foundation Trust Members of Liverpool Health Partners University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6087-9393","authenticated-orcid":false,"given":"Christopher A","family":"Moxon","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Integrative Parasitology Institute of Infection, Immunity and Inflammation University of Glasgow  Glasgow UK"},{"name":"Department of Paediatrics College of Medicine University of Malawi  Blantyre Malawi"},{"name":"Malawi\u2010Liverpool Wellcome Clinical Research Programme College of Medicine University of Malawi  Blantyre Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1305-3529","authenticated-orcid":false,"given":"Aubrey J","family":"Cunnington","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Section of Paediatric Infectious Disease Imperial College London  London UK"},{"name":"Centre for Paediatrics and Child Health Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-012419-032640"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.01.016"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.7861\/clinmed.20-2-s96"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa541"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/587943"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01300-15"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aar3619"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/2045-8118-11-1"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2019.05.003"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0967-12.2012"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz043"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trstmh.2008.11.003"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu592"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2020.03.003"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aaw0336"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1086\/595735"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm986"}],"container-title":["Clinical &amp; Translational Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1263","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cti2.1263","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1263","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T10:47:44Z","timestamp":1693565264000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cti2.1263"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":17,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1002\/cti2.1263"],"URL":"https:\/\/doi.org\/10.1002\/cti2.1263","archive":["Portico"],"relation":{},"ISSN":["2050-0068","2050-0068"],"issn-type":[{"value":"2050-0068","type":"print"},{"value":"2050-0068","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"2020-11-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1263"}}