{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:41:55Z","timestamp":1785415315539,"version":"3.56.0"},"reference-count":82,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University Plovdiv"},{"id":[{"id":"https:\/\/ror.org\/02kzxd152","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Restless legs syndrome (RLS) is one of the most prevalent sleep disorders, yet its diagnosis continues to rely almost entirely on subjective symptom descriptions. This persistent dependence on phenomenology reflects the absence of reliable biological markers to aid in the process of diagnosis or monitoring. However, there is accumulating molecular evidence that suggests that RLS is associated with systemic biological alterations. These extend beyond the traditional paradigm of iron deficiency. The present scoping review synthesizes the current research on circulating serum biomarkers investigated in RLS outside classical iron indices. A comprehensive search of PubMed, Scopus, and Web of Science databases identified 1050 records, of which 50 studies met eligibility criteria and were included. In the processing of data, clusters emerged into several recurring biological domains, including dysregulated iron regulatory signaling (hepcidin), low-grade immune activation, oxidative stress, and neuroaxonal injury markers. High-throughput omics studies reveal molecular network perturbations involving inflammatory pathways, complement activation, metabolic signaling, and cellular stress responses. Biomarker associations appear stronger when linked to objective motor burden. These findings suggest that RLS may involve multifarious molecular changes detectable in the serum. Consequently, this can support the transition from symptom-based diagnosis toward biomarker-informed stratification, which may enable more precise disease characterization and improved diagnostic accuracy.<\/jats:p>","DOI":"10.3390\/ijms27083385","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T12:21:32Z","timestamp":1775737292000},"page":"3385","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum Biomarkers in Restless Legs Syndrome: Beyond the Classical Iron Paradigm\u2014A Scoping Review"],"prefix":"10.3390","volume":"27","author":[{"given":"Krasimir","family":"Avramov","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, Medical University\u2013Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todor","family":"Georgiev","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Medical University\u2013Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneliya","family":"Draganova","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Medical University\u2013Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1314-7039","authenticated-orcid":false,"given":"Kiril","family":"Terziyski","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Medical University\u2013Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1212\/CON.0000000000001269","article-title":"Restless Legs Syndrome and Other Common Sleep-Related Movement Disorders","volume":"29","author":"Khan","year":"2023","journal-title":"Continuum"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"04113","DOI":"10.7189\/jogh.14.04113","article-title":"The Global and Regional Prevalence of Restless Legs Syndrome among Adults: A Systematic Review and Modelling Analysis","volume":"14","author":"Song","year":"2024","journal-title":"J. Glob. Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.jsmc.2021.02.005","article-title":"The Long-Term Psychiatric and Cardiovascular Morbidity and Mortality of Restless Legs Syndrome and Periodic Limb Movements of Sleep","volume":"16","author":"Wipper","year":"2021","journal-title":"Sleep Med. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1001\/jama.2025.23247","article-title":"Restless Legs Syndrome: A Review","volume":"335","author":"Winkelman","year":"2026","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.sleep.2024.11.020","article-title":"Unraveling the Pathophysiology of Restless Legs Syndrome from Multimodal MRI Techniques: A Systematic Review","volume":"125","author":"Pani","year":"2025","journal-title":"Sleep Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4041","DOI":"10.2147\/IJGM.S544680","article-title":"Unraveling Restless Legs Syndrome: A Comprehensive Review of Current Research and Future Directions","volume":"18","author":"Xu","year":"2025","journal-title":"Int. J. Gen. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/s41572-021-00311-z","article-title":"Restless Legs Syndrome","volume":"7","author":"Manconi","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e13632","DOI":"10.1111\/jsr.13632","article-title":"Restless Legs Syndrome: Over 50 Years of European Contribution","volume":"31","author":"Khachatryan","year":"2022","journal-title":"J. Sleep Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S431","DOI":"10.1002\/mds.21824","article-title":"Update of the Pathophysiology of the Restless-Legs-Syndrome","volume":"22","author":"Paulus","year":"2007","journal-title":"Mov. Disord."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.sleep.2016.07.018","article-title":"Brain Imaging and Networks in Restless Legs Syndrome","volume":"31","author":"Rizzo","year":"2017","journal-title":"Sleep Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"103024","DOI":"10.1016\/j.nicl.2022.103024","article-title":"Revisiting Brain Iron Deficiency in Restless Legs Syndrome Using Magnetic Resonance Imaging","volume":"34","author":"Beliveau","year":"2022","journal-title":"Neuroimage Clin."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1016\/j.amjmed.2006.11.003","article-title":"Controversies and Challenges in Defining the Etiology and Pathophysiology of Restless Legs Syndrome","volume":"120","author":"Allen","year":"2007","journal-title":"Am. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.sleep.2004.01.006","article-title":"Subjective and Objective Criteria in the Diagnosis of the Restless Legs Syndrome","volume":"5","author":"Hening","year":"2004","journal-title":"Sleep Med."},{"key":"ref_14","unstructured":"American Academy of Sleep Medicine (2023). The AASM International Classification of Sleep Disorders, American Academy of Sleep Medicine. [3rd ed.]. Text Revision (ICSD-3-TR)."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1371\/journal.pmed.0030170","article-title":"Giving Legs to Restless Legs: A Case Study of How the Media Helps Make People Sick","volume":"3","author":"Woloshin","year":"2006","journal-title":"PLoS Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1212\/WNL.46.1.92","article-title":"A Questionnaire Study of 138 Patients with Restless Legs Syndrome: The \u201cNight-Walkers\u201d Survey","volume":"46","author":"Walters","year":"1996","journal-title":"Neurology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"101949","DOI":"10.1016\/j.smrv.2024.101949","article-title":"Sensory Aspects of Restless Legs Syndrome: Clinical, Neurophysiological and Neuroimaging Prospectives","volume":"76","author":"Antelmi","year":"2024","journal-title":"Sleep Med. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1212\/WNL.0000000000002542","article-title":"Restless Legs Syndrome Associated with Major Diseases A Systematic Review and New Concept","volume":"86","author":"Trenkwalder","year":"2016","journal-title":"Neurology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1056\/NEJMe078129","article-title":"Periodic Limb Movements in Sleep\u2014Endophenotype for Restless Legs Syndrome?","volume":"357","author":"Winkelman","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.smrv.2011.05.002","article-title":"Epidemiology of Restless Legs Syndrome: A Synthesis of the Literature","volume":"16","author":"Ohayon","year":"2012","journal-title":"Sleep Med. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.jsmc.2015.05.004","article-title":"Restless Leg Syndrome Across the Globe: Epidemiology of the Restless Legs Syndrome\/Willis-Ekbom Disease","volume":"10","author":"Koo","year":"2015","journal-title":"Sleep Med. Clin."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/j.sleep.2015.05.022","article-title":"Willis-Ekbom Disease or Restless Legs Syndrome?","volume":"16","author":"Carlos","year":"2015","journal-title":"Sleep Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"137","DOI":"10.5664\/jcsm.11390","article-title":"Treatment of Restless Legs Syndrome and Periodic Limb Movement Disorder: An American Academy of Sleep Medicine Clinical Practice Guideline","volume":"21","author":"Winkelman","year":"2025","journal-title":"J. Clin. Sleep Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.sleep.2017.11.1126","article-title":"Evidence-Based and Consensus Clinical Practice Guidelines for the Iron Treatment of Restless Legs Syndrome\/Willis-Ekbom Disease in Adults and Children: An IRLSSG Task Force Report","volume":"41","author":"Allen","year":"2018","journal-title":"Sleep Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1016\/j.mayocp.2020.12.026","article-title":"The Management of Restless Legs Syndrome: An Updated Algorithm","volume":"96","author":"Silber","year":"2021","journal-title":"Mayo Clin. Proc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41580-023-00648-1","article-title":"Mechanisms Controlling Cellular and Systemic Iron Homeostasis","volume":"25","author":"Galy","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_27","unstructured":"Food and Drug Administration (USA), National Institutes of Health (Bethesda, MD, USA), and FDA-NIH Biomarker Working Group (2026, January 17). BEST (Biomarkers, EndpointS, and Other Tools). Available online: https:\/\/health.uconn.edu\/pepper-center\/wp-content\/uploads\/sites\/272\/2023\/12\/BEST-Biomarkers-EndpointS-and-other-Tools-Resource.pdf."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"467","DOI":"10.7326\/M18-0850","article-title":"PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation","volume":"169","author":"Tricco","year":"2018","journal-title":"Ann. Intern. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.11124\/JBIES-20-00167","article-title":"Updated Methodological Guidance for the Conduct of Scoping Reviews","volume":"18","author":"Peters","year":"2020","journal-title":"JBI Evid. Synth."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Im, H.J., Kim, J.H., Yun, C.H., Kim, D.W., and Oh, J. (2020). Changes in Hepcidin Serum Levels Correlate with Clinical Improvement in Idiopathic Restless Legs Syndrome Patients. J. Clin. Med., 9.","DOI":"10.3390\/jcm9124115"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.sleep.2021.10.008","article-title":"No Association between Plasma Hepcidin Levels and Restless Legs Syndrome\u2014Results from the Danish Blood Donor Study","volume":"88","author":"Dowsett","year":"2021","journal-title":"Sleep Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1002\/mds.27287","article-title":"Association between Serum Hepcidin Level and Restless Legs Syndrome","volume":"33","author":"Dauvilliers","year":"2018","journal-title":"Mov. Disord."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11914","DOI":"10.1038\/s41598-020-68851-0","article-title":"Hepcidin and Ferritin Levels in Restless Legs Syndrome: A Case-Control Study","volume":"10","author":"Chenini","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e3259","DOI":"10.1002\/brb3.3259","article-title":"Evaluation of the Relationship between Idiopathic Restless Legs Syndrome and Serum Hepcidin Levels","volume":"13","author":"Acar","year":"2023","journal-title":"Brain Behav."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s11325-020-02209-8","article-title":"Relation of Serum Hepcidin Levels and Restless Legs Syndrome in Chronic Hemodialysis Patients","volume":"25","author":"Tufekci","year":"2021","journal-title":"Sleep Breath."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Guo, Y., Sang, Y., Pu, T., Li, X., Wang, Y., Yu, L., Liang, Y., Wang, L., Liu, P., and Tang, L. (2021). Relation of Serum Hepcidin Levels and Restless Legs Syndrome in Patients Undergoing Peritoneal Dialysis. Front. Med., 8.","DOI":"10.3389\/fmed.2021.685601"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"109568","DOI":"10.1016\/j.isci.2024.109568","article-title":"Unveiling the Pathophysiology of Restless Legs Syndrome through Transcriptome Analysis","volume":"27","author":"Mogavero","year":"2024","journal-title":"iScience"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S161","DOI":"10.1016\/j.sleh.2023.06.008","article-title":"Proteomic Insights into the Pathophysiology of Periodic Limb Movements and Restless Legs Syndrome","volume":"10","author":"Cederberg","year":"2024","journal-title":"Sleep Health"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e01062","DOI":"10.1002\/brb3.1062","article-title":"Discovery of Restless Legs Syndrome Plasmatic Biomarkers by Proteomic Analysis","volume":"8","author":"Bellei","year":"2018","journal-title":"Brain Behav."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.sleep.2020.09.002","article-title":"Bioinformatic Analysis of Proteomic Data for Iron, Inflammation, and Hypoxic Pathways in Restless Legs Syndrome","volume":"75","author":"Shin","year":"2020","journal-title":"Sleep Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"873","DOI":"10.2147\/NSS.S311801","article-title":"Searching for Novel Candidate Biomarkers of Rls in Blood by Proteomic Analysis","volume":"13","author":"Mondello","year":"2021","journal-title":"Nat. Sci. Sleep"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s11306-022-01938-z","article-title":"A Metabolic Biomarker Panel of Restless Legs Syndrome in Peritoneal Dialysis Patients","volume":"18","author":"Yang","year":"2022","journal-title":"Metabolomics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"107477","DOI":"10.1016\/j.clineuro.2022.107477","article-title":"Possible Association between Vitamin B12 Deficiency and Restless Legs Syndrome","volume":"223","author":"Geng","year":"2022","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"112851","DOI":"10.1016\/j.exger.2025.112851","article-title":"Telomere Length in Sleep Disorders","volume":"209","author":"Amraliyev","year":"2025","journal-title":"Exp. Gerontol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"107944","DOI":"10.1016\/j.parkreldis.2025.107944","article-title":"Clinical Feature and Alpha-Synuclein Level of Restless Legs Syndrome with Leucine-Rich Repeat Kinase 2 Encoding Gene Mutation","volume":"138","author":"Guo","year":"2025","journal-title":"Park. Relat. Disord."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.sleep.2011.11.012","article-title":"Assessment of Nitric Oxide, Advanced Oxidation Protein Products, Malondialdehyde, and Thiol Levels in Patients with Restless Legs Syndrome","volume":"13","author":"Baskol","year":"2012","journal-title":"Sleep Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.sleep.2015.03.025","article-title":"Association of Restless Legs Syndrome with Oxidative Stress and Inflammation in Patients Undergoing Hemodialysis","volume":"16","author":"Higuchi","year":"2015","journal-title":"Sleep Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"106694","DOI":"10.1016\/j.sleep.2025.106694","article-title":"Association between Serum GFAP, BDNF and NfL Levels and Clinical Symptoms in Restless Legs Syndrome: A Case-Control Study","volume":"134","author":"Yan","year":"2025","journal-title":"Sleep Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1007\/s00415-020-10312-9","article-title":"Serum Vitamin D, Vitamin D Receptor and Binding Protein Genes Polymorphisms in Restless Legs Syndrome","volume":"268","author":"Amo","year":"2021","journal-title":"J. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1007\/s00702-019-02051-7","article-title":"Evaluation of Potential Cardiovascular Risk Protein Biomarkers in High Severity Restless Legs Syndrome","volume":"126","author":"Bellei","year":"2019","journal-title":"J. Neural Transm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s13760-019-01177-5","article-title":"Assessment of Serum Uric Acid Levels in Patients with Restless Legs Syndrome","volume":"119","author":"Yazar","year":"2019","journal-title":"Acta Neurol. Belg."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2933","DOI":"10.1021\/acs.jproteome.9b00549","article-title":"Serum Glycomics Profiling of Patients with Primary Restless Legs Syndrome Using LC-MS\/MS","volume":"19","author":"Dong","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1159\/000355727","article-title":"Uremic Restless Legs Syndrome (RLS) and Sleep Quality in Patients with End-Stage Renal Disease on Hemodialysis: Potential Role of Homocysteine and Parathyroid Hormone","volume":"37","author":"Gade","year":"2013","journal-title":"Kidney Blood Press. Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Jim\u00e9nez-Jim\u00e9nez, F.J., Ayuso, P., Alonso-Navarro, H., Calleja, M., D\u00edez-Fair\u00e9n, M., \u00c1lvarez, I., Pastor, P., Plaza-Nieto, J.F., Navarro-Mu\u00f1oz, S., and Turp\u00edn-Fenoll, L. (2022). Serum Trace Elements Concentrations in Patients with Restless Legs Syndrome. Antioxidants, 11.","DOI":"10.3390\/antiox11020272"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Mitchell, U.H., Obray, J.D., Hunsaker, E., Garcia, B.T., Clarke, T.J., Hope, S., and Steffensen, S.C. (2018). Peripheral Dopamine in Restless Legs Syndrome. Front. Neurol., 9.","DOI":"10.3389\/fneur.2018.00155"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Huang, Y.X., Zhang, Q.L., Huang, C.L., Wu, W.Q., and Sun, J.W. (2021). Association of Decreased Serum BDNF with Restless Legs Syndrome in Parkinson\u2019s Disease Patients. Front. Neurol., 12.","DOI":"10.3389\/fneur.2021.734570"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1515\/cclm-2020-1659","article-title":"Plasma Thiol\/Disulphide Homeostasis Changes in Patients with Restless Legs Syndrome","volume":"59","author":"Kucuksayan","year":"2021","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1002\/ana.10843","article-title":"Circadian Rhythm of Restless Legs Syndrome: Relationship with Biological Markers","volume":"55","author":"Michaud","year":"2004","journal-title":"Ann. Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1111\/ane.12866","article-title":"Plasma Copeptin Levels in Patients with Restless Legs Syndrome","volume":"137","author":"Ozben","year":"2018","journal-title":"Acta Neurol. Scand."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"zsz079","DOI":"10.1093\/sleep\/zsz079","article-title":"Extracellular Vesicles Reveal Abnormalities in Neuronal Iron Metabolism in Restless Legs Syndrome","volume":"42","author":"Chawla","year":"2019","journal-title":"Sleep"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"101744","DOI":"10.1016\/j.smrv.2022.101744","article-title":"Inflammatory Factors and Restless Legs Syndrome: A Systematic Review and Meta-Analysis","volume":"68","year":"2023","journal-title":"Sleep Med. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Jim\u00e9nez-Jim\u00e9nez, F.J., Ayuso, P., Alonso-Navarro, H., Calleja, M., \u00c1lvarez, I., Pastor, P., Navarro-Mu\u00f1oz, S., Turp\u00edn-Fenoll, L., Mill\u00e1n-Pascual, J., and Garc\u00eda-Albea, E. (2026). Serum Concentrations of Cytokines in Patients With Restless Legs Syndrome. J. Sleep Res., e70293.","DOI":"10.1111\/jsr.70293"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1111\/1744-9987.12313","article-title":"Relationships Between Malnutrition, Inflammation, Sleep Quality, and Restless Legs Syndrome in Hemodialysis Patients","volume":"19","author":"Kaya","year":"2015","journal-title":"Ther. Apher. Dial."},{"key":"ref_64","first-page":"437","article-title":"Serum Iron, Hemoglobin, CRP and Calcium in Hemodialysis Patients with and without Restless Legs Syndrome","volume":"7","author":"Nasiri","year":"2015","journal-title":"Sch. Res. Libr. Der Pharm. Lett."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/j.bbi.2012.06.003","article-title":"Elevated C-Reactive Protein Is Associated with Severe Periodic Leg Movements of Sleep in Patients with Restless Legs Syndrome","volume":"26","author":"Trotti","year":"2012","journal-title":"Brain Behav. Immun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1093\/ndt\/gfq681","article-title":"Restless Legs Syndrome Enhances Cardiovascular Risk and Mortality in Patients with End-Stage Kidney Disease Undergoing Long-Term Haemodialysis Treatment","volume":"26","author":"Pizza","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1007\/s11325-016-1359-3","article-title":"To What Extent and Why Are COPD and Willis-Ekbom Disease Associated?","volume":"20","author":"Mandal","year":"2016","journal-title":"Sleep Breath."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1365-2869.2009.00739.x","article-title":"Prevalence, Comorbidities and Risk Factors of Restless Legs Syndrome in the Korean Elderly Population\u2014Results from the Korean Longitudinal Study on Health and Aging","volume":"19","author":"Kim","year":"2010","journal-title":"J. Sleep Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jpsychores.2018.09.008","article-title":"Elevation of Tumor Necrosis Factor Alpha Levels Is Associated with Restless Legs Symptoms in Clinically Depressed Patients","volume":"115","author":"Auvinen","year":"2018","journal-title":"J. Psychosom. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"259","DOI":"10.4274\/tnd.98474","article-title":"Evaluation of Inflammation with Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Restless Legs Syndrome","volume":"24","author":"Tak","year":"2018","journal-title":"Turk. J. Neurol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.sleep.2019.02.022","article-title":"Serum C-Reactive Protein\/Albumin Ratio and Restless Legs Syndrome","volume":"58","author":"Yazar","year":"2019","journal-title":"Sleep Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1038\/s41598-022-05658-1","article-title":"Chronic Inflammation Markers and Cytokine-Specific Autoantibodies in Danish Blood Donors with Restless Legs Syndrome","volume":"12","author":"Dowsett","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Dowsett, J., Didriksen, M., Larsen, M.H., Dinh, K.M., Kaspersen, K.A., Mikkelsen, S., Th\u00f8rner, L.W., S\u00f8rensen, E., Erikstrup, C., and Pedersen, O.B. (2021). Investigating the Inflammation Marker Neutrophil-to-Lymphocyte Ratio in Danish Blood Donors with Restless Legs Syndrome. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0259681"},{"key":"ref_74","first-page":"e51671","article-title":"Investigation of the Albumin\/Globulin Ratio as a Biomarker in Restless Legs Syndrome","volume":"16","year":"2024","journal-title":"Cureus"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"94","DOI":"10.4103\/jnrp.jnrp_159_18","article-title":"Serum Interleukin-6 Is Not Linked with Sleep-Quality, Restless Legs Syndrome, and Depression, but with 6-Month Survival in Hematological Malignancies","volume":"10","author":"Chandra","year":"2019","journal-title":"J. Neurosci. Rural Pract."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5765","DOI":"10.1007\/s10072-024-07736-w","article-title":"Association between Inflammatory Cytokines and Disease Severity in Restless Legs Syndrome","volume":"45","author":"Geng","year":"2024","journal-title":"Neurol. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"107056","DOI":"10.1016\/j.imlet.2025.107056","article-title":"Immune Cells and Functions in Patients with Restless Legs Syndrome","volume":"276","author":"Kokoglu","year":"2025","journal-title":"Immunol. Lett."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1007\/s11325-020-02218-7","article-title":"Circulating Levels of Cytokines Are Increased in Restless Legs Syndrome","volume":"25","author":"Uslu","year":"2021","journal-title":"Sleep Breath."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.sleep.2010.08.006","article-title":"Prevalence of Restless Legs Syndrome among Adults in Iceland and Sweden: Lung Function, Comorbidity, Ferritin, Biomarkers and Quality of Life","volume":"11","author":"Benediktsdottir","year":"2010","journal-title":"Sleep Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.jns.2006.04.008","article-title":"Is Ferroportin-Hepcidin Signaling Altered in Restless Legs Syndrome?","volume":"247","author":"Clardy","year":"2006","journal-title":"J. Neurol. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/s41419-022-05043-w","article-title":"Astrocyte-Derived Hepcidin Controls Iron Traffic at the Blood-Brain-Barrier via Regulating Ferroportin 1 of Microvascular Endothelial Cells","volume":"13","author":"You","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.smrv.2011.09.003","article-title":"Restless Legs Syndrome\u2014Theoretical Roles of Inflammatory and Immune Mechanisms","volume":"16","author":"Weinstock","year":"2012","journal-title":"Sleep Med. Rev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3385\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T12:25:21Z","timestamp":1775737521000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3385"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,9]]},"references-count":82,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27083385"],"URL":"https:\/\/doi.org\/10.3390\/ijms27083385","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,9]]}}}