title: Decreased level of sRAGE in the cerebrospinal fluid of multiple sclerosis patients at clinical onset.
abstract: OBJECTIVE
  Receptor for advanced glycation end products (RAGE) ligands/RAGE interactions have been proposed to have a pathogenic role in neuroinflammatory disorders. Our study aimed to assess changes in high-mobility group box (HMGB)1 and its receptor RAGE in peripheral blood (PBL) and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) at the disease onset compared with control subjects.
  
  
  METHODS
  PBL and CSF were collected from control subjects (n = 30) and MS patients (n = 27) at clinical onset. Soluble RAGE (sRAGE), HMGB1, S100 calcium-binding protein A12 (S100A12), interleukin (IL)-1β and tumor necrosis factor (TNF)-α were measured in the CSF and plasma by enzyme-linked immunosorbent assay. Gene expression in PBL mononuclear cells (PBMCs) was detected by quantitative PCR for RAGE, HMGB1, S100A12 and several proinflammatory/immunoregulatory cytokines.
  
  
  RESULTS
  We found a significantly lower expression of IL-10 (p = 0.031) in the PBMCs of MS patients. The level of sRAGE in the CSF of MS patients was lower (p = 0.021), with the ability to discriminate between MS patients and control subjects. Moreover, PBMC gene expression for HMGB1 and S100A12 positively correlated with IL-6.
  
  
  CONCLUSIONS
  Our study confirmed that the cytokine network is disturbed in PBL and CSF at MS clinical onset. The deregulated HMGB1/RAGE axis found in our study may present an early pathogenic event in MS, proposing sRAGE as a possible novel therapeutic strategy for MS treatment.
authors.affiliation: Department of Physiology and Immunology, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Anton
authors.initials: A
authors.lastname: Glasnović
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Cvija
authors.forename: Maristela
authors.initials: M
authors.lastname: Stojić
authors.forename: Ivana
authors.initials: I
authors.lastname: Tudorić-Đeno
authors.forename: Sanja
authors.initials: S
authors.lastname: Ivčević
authors.forename: Dominik
authors.initials: D
authors.lastname: Romić
authors.forename: Nino
authors.initials: N
authors.lastname: Tičinović
authors.forename: Vladimira
authors.initials: V
authors.lastname: Vuletić
authors.forename: Ines
authors.initials: I
authors.lastname: Lazibat
authors.forename: Danka
authors.initials: D
authors.lastname: Grčević
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D002630:Chemotactic Factors / Q000097:blood / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D024243:HMGB1 Protein / Q000097:blood* / Q000134:cerebrospinal fluid; D006801:Humans; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000134:cerebrospinal fluid*; D060888:Real-Time Polymerase Chain Reaction; D000067759:Receptor for Advanced Glycation End Products / Q000097:blood; D009418:S100 Proteins / Q000097:blood / Q000134:cerebrospinal fluid; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D002630:Chemotactic Factors; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D000067759:Receptor for Advanced Glycation End Products; D009418:S100 Proteins; C098997:S100A2 protein, human