Mogavero Maria P, Peng Gang, Marchese Giovanna, Lanza Giuseppe, Ferini-Strambi Luigi, Ferri Raffaele, Koo Brian B
Vita-Salute San Raffaele University, 20132 Milan, Italy.
San Raffaele Scientific Institute, Division of Neuroscience, Sleep Disorders Center, 20127 Milan, Italy.
Sleep. 2025 Apr 26. doi: 10.1093/sleep/zsaf112.
The pathobiology of restless legs syndrome (RLS) remains poorly understood, complicating effective treatment. This observational cross-sectional study aimed to identify a cerebrospinal fluid proteomic signature of RLS and to explore sex-specific differences in cerebrospinal fluid proteomics.
Cerebrospinal fluid samples were collected from 22 untreated RLS patients and 18 controls, matched for age, body mass index, and sex. Proteomic analysis was conducted using the SOMAscan® platform, assessing over 7,000 peptides.
Eight proteins were differentially abundant between patients and controls, with CRP and JAML increased, and TAPBPL and IL1RL1 decreased. Pathway analysis highlighted significant involvement in immune response, coagulation, and cytoskeletal regulation. Analyses were then carried out with sex stratification, comparing separately men and women. Sex-specific analyses revealed more pronounced proteomic alterations in males (68 differentially abundant proteins vs. control males) than females (17 proteins). Gene enrichment analysis revealed that men with RLS had more involvement of gene regulation and epigenetic factors than control males and women with restless legs syndrome had greater involvement of systemic inflammatory and vascular processes than control females.
This study identified a cerebrospinal fluid proteomic signature in RLS, implicating immune and inflammatory pathways in the disease's pathophysiology. Significant sex differences in protein level suggest potential sex-specific mechanisms in RLS, warranting further investigation. These findings contribute to the current understanding of RLS and could inform future therapeutic strategies.
不宁腿综合征（RLS）的病理生物学仍未得到充分了解，这使得有效治疗变得复杂。这项观察性横断面研究旨在确定RLS的脑脊液蛋白质组学特征，并探索脑脊液蛋白质组学中的性别差异。
从22名未经治疗的RLS患者和18名对照者中收集脑脊液样本，这些对照者在年龄、体重指数和性别方面进行了匹配。使用SOMAscan®平台进行蛋白质组学分析，评估超过7000种肽。
患者和对照者之间有8种蛋白质丰度存在差异，CRP和JAML增加，TAPBPL和IL1RL1减少。通路分析突出显示在免疫反应、凝血和细胞骨架调节中存在显著参与。然后进行性别分层分析，分别比较男性和女性。性别特异性分析显示，男性（与对照男性相比有68种丰度差异的蛋白质）的蛋白质组学改变比女性（17种蛋白质）更明显。基因富集分析显示，患有RLS的男性比对照男性更多地参与基因调控和表观遗传因素，而患有不宁腿综合征的女性比对照女性更多地参与全身炎症和血管过程。
本研究确定了RLS的脑脊液蛋白质组学特征，表明免疫和炎症通路参与了该疾病的病理生理学。蛋白质水平上的显著性别差异表明RLS中可能存在性别特异性机制，值得进一步研究。这些发现有助于当前对RLS的理解，并可为未来的治疗策略提供参考。
