Discovery of restless legs syndrome plasmatic biomarkers by proteomic analysis

Abstract

ObjectivesRestless legs syndrome (RLS) can lead to severe clinical consequences, thus negatively impacts on patients’ overall health and quality of life. Nevertheless, the pathophysiology of RLS is still unclear, resulting in underestimate, incorrect, or ignored diagnosis and in limited management and treatment. The aim of this study was to compare the plasma proteome of RLS patients and healthy controls, in the search of diagnostic biomarkers related to the disease severity.Materials and MethodsTwo‐dimensional gel electrophoresis coupled with liquid chromatography‐mass spectrometry was employed to analyze plasma samples of 34 patients with primary RLS, divided into two subgroups according to the disease severity: MMS group (mild‐moderate symptoms) and HS group (severe and very severe symptoms), and 17 age‐ and sex‐matched control subjects. Sleep quality, daytime sleepiness, and the level of depression were also evaluated.ResultsWe identified eight upregulated spots, corresponding to five unique proteins, in both RLS group vs. controls (alpha‐1B‐glycoprotein, alpha‐1‐acid glycoprotein 1, haptoglobin, complement C4‐A, and immunoglobulin kappa constant); five increased spots, consistent with three unique proteins, only in HS‐RLS (kininogen‐1, immunoglobulin heavy constant alpha 1, and immunoglobulin lambda constant 2); one downregulated spot in both patient's groups (complement C3) and another one only in HS‐RLS (alpha‐1‐antitrypsin).ConclusionsThe significantly different plasma proteins detected in RLS were mainly associated with inflammation, immune response, and cardiovascular disorders. Particularly, the gradual increasing in immunoglobulins could be indicative of the disease severity and evolution. Accordingly, these proteins may represent a valid set of useful biomarkers for RLS diagnosis, progression and treatment.

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

“…In line with the results of the proteomic analysis by Bellei et al, 33 in our study, the concentration of A 1 AT was substantial in RLS patients. A 1 AT has pleiotropic effects, having been shown an association with pathways of inflammation, memory disorders, pregnancy, and cardiovascular disease as well as activation of antioxidant enzymes, suppression of oxidation stress, and decrease apoptosis.…”

“… 74 This is prominently denoted in Figure 1A and D . In the study by Bellei et al, 33 Hp was characteristically found to be upregulated; The discrepant results may result from the inclusion in this study of RLS patients on medications, which might have affected the results of the proteomic analysis. In our study, the differential regulation of Hp might be also related to a chronic inflammatory milieu involved in the modulation of RLS.…”

“…Only few proteomic studies were previously conducted, one using cerebrospinal fluid (CSF) 32 and other blood plasma. 33–36 The latter represents a better resource for biomarkers, as they should be not only highly sensitive and specific but also easily attainable. 37 …”

Electric Stimulation of Neurogenesis Improves Behavioral Recovery After Focal Ischemia in Aged Rats

“…Transcripts that were upregulated in the peri-infarcted area both by ES and lesion included genes of immunoglobulin heavy chain involved in B cells development which were knew to stroke and schizophrenia ( Pandey et al, 2018 ) but also genes involved in Ataxia telangiectasia [immunoglobulin J polypeptide (IgJ)] ( Castro and Flajnik, 2014 ; Steinel et al, 2014 ), Fc domain of Ig that binds to a cell surface receptor (Fcris) which is secreted by activated microglia in neurodegenerative diseases like Alzheimer‘ disease ( Bisht et al, 2018 ) as well as Ig kappa chain V–III region MOPC 6-like (LOC50284) involved in the Restless legs syndrome ( Bellei et al, 2018 ) ( Table 1 ).…”

Are Mannan-binding Lectine Serin Protease-2 and Alpha-1-microglobulin and Bukinin Precursor the Potential Biomarkers of Manic Episode? A Study via Urinary Proetomic Analysis

“…Alpha-1B-glycoprotein is a secreted plasma protein and a member of the immunoglobulin superfamily with a reasonable role in the immune system and in cell adhesion. Bellei et al [35] revealed increased alpha-1B-glycoprotein by proteomic analysis of plasma samples of patients with restless leg syndrome. Biswas et al [36] have identified, by an immunoproteomic approach, a higher expression of alpha-1B-glycoprotein in synovial fluid of patients with rheumatoid arthritis, proposing this glycoprotein as a biomarker of diagnostic importance for rheumatoid arthritis.…”