{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:44:30Z","timestamp":1789152270313,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2021\u201002814"],"award-info":[{"award-number":["2021\u201002814"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011898","name":"Marcus och Amalia Wallenbergs minnesfond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011898","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003748","name":"Svenska S\u00e4llskapet f\u00f6r Medicinsk Forskning","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003748","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the utility of cerebrospinal fluid (CSF) biomarkers\u2014matrix metalloproteinase\u20109 (MMP\u20109), tissue inhibitor of metalloproteinases\u20101 (TIMP\u20101), the MMP\u20109\/TIMP\u20101 ratio, and osteopontin (OPN)\u2014as indicators of blood\u2013brain barrier (BBB) integrity and disease activity in people with relapsing\u2013remitting multiple sclerosis (pwMS), and to assess their changes following autologous hematopoietic stem cell transplantation (aHSCT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      CSF samples from pwMS treated with aHSCT (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200943) and healthy controls (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200932) were analyzed for MMP\u20109, TIMP\u20101, and OPN concentrations using ELISA and electrochemiluminescence assays. Lumbar punctures were performed at baseline and at 1, 2, and 3\u20135\u2009years post\u2010aHSCT. Biomarker findings were compared with standard CSF parameters, prior treatments, and MRI data.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MMP\u20109\/TIMP\u20101 ratios and OPN levels were significantly elevated in pwMS compared to controls, particularly in those with gadolinium\u2010enhancing lesions or on first\u2010line therapies. Both biomarkers declined significantly after aHSCT and remained low during follow\u2010up. The MMP\u20109\/TIMP\u20101 ratio showed superior discriminatory capacity and correlated with inflammatory CSF markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>CSF MMP\u20109\/TIMP\u20101 ratio and OPN are elevated in MS and decrease following aHSCT, reflecting reduced inflammation and restored BBB integrity. These biomarkers may support disease monitoring and therapeutic evaluation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70229","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T05:50:17Z","timestamp":1760507417000},"page":"442-452","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The\n                    <scp>MMP<\/scp>\n                    \u20109\/\n                    <scp>TIMP<\/scp>\n                    \u20101 Ratio and Concentrations of Osteopontin Are Elevated in Cerebrospinal Fluid of People With Multiple Sclerosis and Decrease After Autologous Hematopoietic Stem Cell Transplantation"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7832-3083","authenticated-orcid":false,"given":"Ivan","family":"Pavlovic","sequence":"first","affiliation":[{"name":"Translational Neurology, Department of Medical Sciences Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Erngren","sequence":"additional","affiliation":[{"name":"Clinical Chemistry, Department of Medical Sciences Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Kultima","sequence":"additional","affiliation":[{"name":"Clinical Chemistry, Department of Medical Sciences Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Larsson","sequence":"additional","affiliation":[{"name":"Clinical Chemistry, Department of Medical Sciences Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malin","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Translational Neurology, Department of Medical Sciences Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Wiberg","sequence":"additional","affiliation":[{"name":"Translational Neurology, Department of Medical Sciences Uppsala University  Uppsala Sweden"},{"name":"Clinical Immunology, Department of Immunology, Genetics &amp; Pathology Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Burman","sequence":"additional","affiliation":[{"name":"Translational Neurology, Department of Medical Sciences Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(23)00377\u20100"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022\u2010510x(70)90156\u20105"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-195001000-00009"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.10.020"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22168370"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458510370791"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458512466929"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.60.1.52"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1191\/135248506ms1274oa"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1062960"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.105785"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/nxi.0000000000200265"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102023\u2010331864"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.281053"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(17)30470\u20102"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181c47cc2"},{"key":"e_1_2_9_18_1","unstructured":"GraphPad Software accessed August 23 2021 http:\/\/www.graphpad.com."},{"key":"e_1_2_9_19_1","first-page":"2629","volume-title":"Statistics in Medicine","author":"Wechsler S.","year":"1997"},{"key":"e_1_2_9_20_1","unstructured":"Affinity Designer accessed December 10 2022 https:\/\/www.affinity.serif.com."},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13014"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(15)00393\u20102"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1191\/1352458505ms1193oa"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458514560925"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10606"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2004.06.007"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458510382247"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2007.33"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201003173\u20103"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000361"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468\u20101331.2009.02532.x"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.70229","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acn3.70229","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.70229","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T06:44:50Z","timestamp":1773038690000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.70229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,14]]},"references-count":30,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/acn3.70229"],"URL":"https:\/\/doi.org\/10.1002\/acn3.70229","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,14]]},"assertion":[{"value":"2025-04-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}