{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T13:31:00Z","timestamp":1786627860469,"version":"build-2736575974"},"reference-count":15,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"abstract":"ABSTRACT<\/jats:title>\n \n Objective<\/jats:title>\n \n Susac syndrome (SS) is a rare CD8\n +<\/jats:sup>\n T cell\u2013mediated microangiopathy affecting the brain, retina, and auditory labyrinth. Endothelial injury is thought to be a central mechanism; however, no circulating disease biomarkers are known. We performed targeted proteomic profiling to identify circulating endothelial\u2010associated proteins as biomarkers in SS.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Serum from four cases with definite or probable SS and eight healthy controls was analyzed using data\u2010independent acquisition mass spectrometry. Analyses were restricted to proteins with established endothelial cell surface or membrane association, and differential abundance was assessed using detection\u2010based (Fisher's exact) and quantitative (probabilistic dropout analysis) modeling.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Six endothelial\u2010associated proteins demonstrated differential abundance in SS (\n p<\/jats:italic>\n \u2009<\u20090.05 on unadjusted analysis). Low\u2010density lipoprotein receptor\u2010related protein 1 was increased (log\n 2<\/jats:sub>\n fold change\u2009=\u2009+2.19,\n p<\/jats:italic>\n \u2009=\u20090.0059), whereas Nectin\u20102, Melanoma cell adhesion molecule, Fatty acid transport protein 4, P\u2010selectin, and Interleukin\u20106 signal transducer were decreased (log\n 2<\/jats:sub>\n fold change \u22121.38 to \u22121.89; all\n p<\/jats:italic>\n \u2009<\u20090.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Our findings suggest circulating proteins on the endothelial cell surface or membrane as potential biomarkers for SS and support endothelial dysfunction as a central disease mechanism. This pilot study provides a rationale for validation in larger, longitudinal cohorts.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n ClinicalTrials.gov, NCT00001248 and NCT02435810<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/acn3.70508","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T12:41:16Z","timestamp":1786624876000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Endothelial Cell Proteins as Biomarkers in Susac Syndrome"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1124-8119","authenticated-orcid":false,"given":"Rohit","family":"Benjamin","sequence":"first","affiliation":[{"name":"Section of Infections of the Nervous System National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue Andy","family":"Qi","sequence":"additional","affiliation":[{"name":"Center for Alzheimer's and Related Dementias (CARD) National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Hao","sequence":"additional","affiliation":[{"name":"Center for Alzheimer's and Related Dementias (CARD) National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"DeMarino","sequence":"additional","affiliation":[{"name":"Section of Infections of the Nervous System National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Darko","sequence":"additional","affiliation":[{"name":"Section of Infections of the Nervous System National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Cortese","sequence":"additional","affiliation":[{"name":"Experimental Immunotherapeutics Unit National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S.","family":"Reich","sequence":"additional","affiliation":[{"name":"Translational Neuroradiology Section National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda I.","family":"Gait\u00e1n","sequence":"additional","affiliation":[{"name":"Translational Neuroradiology Section National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Viral Immunology Section National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridgett J.","family":"Billioux","sequence":"additional","affiliation":[{"name":"Program in International Neuroinfectious Diseases National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Neurology DC Veterans Affairs Medical Center Washington, DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0927-5855","authenticated-orcid":false,"given":"Avindra","family":"Nath","sequence":"additional","affiliation":[{"name":"Section of Infections of the Nervous System National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.29.3.313"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201013593\u20105"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2010.08.043"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.a6103"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742\u20102094\u201011\u201046"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPERI7LC4VNFYK"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102016\u2010314295"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crmeth.2023.100593"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/gpbjnl\/qzae083"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00033.2007"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12987\u2010021\u201000260\u20105"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines8120592"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.312653"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2457"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.70"}],"container-title":["Annals 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