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Article Dans Une Revue Sleep Année : 2022

Proteomic biomarkers of Kleine–Levin syndrome

Katie L Cederberg
Aditya Ambati
Ling Lin
  • Fonction : Auteur
Neal Farber
Yu-Shu Huang
Emmanuel Mignot

Résumé

Study Objectives Kleine–Levin syndrome (KLS) is characterized by relapsing–remitting episodes of hypersomnia, cognitive impairment, and behavioral disturbances. We quantified cerebrospinal fluid (CSF) and serum proteins in KLS cases and controls. Methods 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. Results Univariate analyses found 28 and 141 proteins differentially expressed in CSF and serum, respectively (false discovery rate <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–brain 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 < 6 × 10−5), 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] = 0.78–1.0, p = 0.0006) in CSF and 1.0 (95% CI = 1.0–1.0, 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. Conclusions Our study identifies proteomic KLS biomarkers with diagnostic potential and provides insight into biological mechanisms that will guide future research in KLS.
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hal-04438815 , version 1 (19-02-2024)

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Julien Hédou, Katie L Cederberg, Aditya Ambati, Ling Lin, Neal Farber, et al.. Proteomic biomarkers of Kleine–Levin syndrome. Sleep, 2022, 45 (9), pp.zsac097. ⟨10.1093/sleep/zsac097⟩. ⟨hal-04438815⟩
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