4.5 Article

Searching for Novel Candidate Biomarkers of RLS in Blood by Proteomic Analysis

期刊

NATURE AND SCIENCE OF SLEEP
卷 13, 期 -, 页码 873-883

出版社

DOVE MEDICAL PRESS LTD
DOI: 10.2147/NSS.S311801

关键词

idiopathic restless legs syndrome; biomarkers; LC-MS/MS; proteome; interactome

资金

  1. Italian Ministry of Health Ricerca Corrente [2634472]

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Comparative proteomic analysis of blood samples from patients with RLS and healthy individuals identified multiple proteins associated with RLS, highlighting the multifactorial nature of the disease. The study also revealed a set of circulating proteins that may have clinical importance as biomarkers and therapeutic targets for RLS.
Purpose: We performed comparative proteomic analyses of blood of patients with RLS and healthy individuals aiming to identify potential biomarker and therapeutic target candidate for RLS. Patients and Methods: Blood serum samples from 12 patients with a clinical diagnosis of RLS (8 females and 4 males, with a mean age of 68.52 years) and 10 healthy controls (5 females and 5 males, with a mean age of 67.61 years) underwent proteomic profiling by liquid chromatography coupled with tandem mass spectrometry. Pathway analysis incorporating protein-protein interaction networks was carried out to identify pathological processes linked to the differentially expressed proteins. Results: We quantified 272 proteins in patients with RLS and healthy controls, of which 243 were shared. Five proteins - apolipoprotein C-II, leucine-rich alpha-2-glycoprotein 1, FLJ92374, extracellular matrix protein 1, and F1193143 - were substantially increased in RLS patients, whereas nine proteins - vitamin D-binding protein, FLJ78071, alpha-1-antitrypsin, CD5 antigen-like, haptoglobin, fibrinogen alpha chain, complement factor H-related protein 1, platelet factor 4, and plasma protease Cl inhibitor - were decreased. Bioinformatics analyses revealed that these proteins were linked to 1) inflammatory and immune response, and complement activation, 2) brain-related development, cell aging, and memory disorders, 3) pregnancy and associated complications, 4) myocardial infarction, and 5) reactive oxygen species generation and subsequent diabetes mellitus. Conclusion: Our findings shed light on the multifactorial nature of RLS and identified a set of circulating proteins that may have clinical importance as biomarkers and therapeutic targets.

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