{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:19:11Z","timestamp":1791357551438,"version":"4.3.1"},"reference-count":81,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T00:00:00Z","timestamp":1658361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100003919","name":"Kleine Levin Syndrome foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100003919","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01MH080957"],"award-info":[{"award-number":["R01MH080957"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["1S10OD023452-01"],"award-info":[{"award-number":["1S10OD023452-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Study Objectives<\/jats:title><jats:p>Kleine\u2013Levin syndrome (KLS) is characterized by relapsing\u2013remitting episodes of hypersomnia, cognitive impairment, and behavioral disturbances. We quantified cerebrospinal fluid (CSF) and serum proteins in KLS cases and controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>SomaScan was used to profile 1133 CSF proteins in 30 KLS cases and 134 controls, while 1109 serum proteins were profiled in serum from 26 cases and 65 controls. CSF and serum proteins were both measured in seven cases. Univariate and multivariate analyses were used to find differentially expressed proteins (DEPs). Pathway and tissue enrichment analyses (TEAs) were performed on DEPs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Univariate analyses found 28 and 141 proteins differentially expressed in CSF and serum, respectively (false discovery rate &amp;lt;0.1%). Upregulated CSF proteins included IL-34, IL-27, TGF-b, IGF-1, and osteonectin, while DKK4 and vWF were downregulated. Pathway analyses revealed microglial alterations and disrupted blood\u2013brain barrier permeability. Serum profiles show upregulation of Src-family kinases (SFKs), proteins implicated in cellular growth, motility, and activation. TEA analysis of up- and downregulated proteins revealed changes in brain proteins (p &amp;lt; 6 \u00d7 10\u22125), notably from the pons, medulla, and midbrain. A multivariate machine-learning classifier performed robustly, achieving a receiver operating curve area under the curve of 0.90 (95% confidence interval [CI] = 0.78\u20131.0, p = 0.0006) in CSF and 1.0 (95% CI = 1.0\u20131.0, p = 0.0002) in serum in validation cohorts, with some commonality across tissues, as the model trained on serum sample also discriminated CSF samples of controls versus KLS cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study identifies proteomic KLS biomarkers with diagnostic potential and provides insight into biological mechanisms that will guide future research in KLS.<\/jats:p><\/jats:sec>","DOI":"10.1093\/sleep\/zsac097","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T05:08:26Z","timestamp":1658380106000},"source":"Crossref","is-referenced-by-count":11,"title":["Proteomic biomarkers of Kleine\u2013Levin syndrome"],"prefix":"10.1093","volume":"45","author":[{"given":"Julien","family":"H\u00e9dou","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Center for Sleep Sciences and Medicine, Stanford University , Palo Alto, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5693-9293","authenticated-orcid":false,"given":"Katie L","family":"Cederberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Center for Sleep Sciences and Medicine, Stanford University , Palo Alto, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8462-3552","authenticated-orcid":false,"given":"Aditya","family":"Ambati","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Center for Sleep Sciences and Medicine, Stanford University , Palo Alto, CA , 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