title: Disease modifying drugs modulate endogenous secretory receptor for advanced glycation end-products, a new biomarker of clinical relapse in multiple sclerosis.
abstract: OBJECTIVE
  This study is one in a series measuring RAGE axis (receptor for advanced glycation end products, its isoforms, and ligands) and its potential as a biomarker in multiple sclerosis (MS). We evaluated serum levels of the endogenous secretory RAGE (esRAGE) in MS patients and assessed the relationship between esRAGE levels and the use of disease modifying drugs (DMDs), and between esRAGE levels and indicators of MS disease severity.
  
  
  METHODS
  esRAGE serum levels were compared between 98 MS patients and 34 healthy controls (HCs) using ELISA.
  
  
  RESULTS
  esRAGE serum levels were similar between MS and HCs. DMD-treated patients had higher esRAGE serum levels than DMD-naïve patients (395.7±38.6pg/ml vs. 299.2±20.1pg/ml, P=0.02). DMD-naïve, primary progressive (PP) patients had higher esRAGE serum levels, than relapsing remitting (RR) (P=0.02) and secondary progressive (SP) (P=0.04) patients; RRMS patients in clinical relapse had lower esRAGE serum levels than clinically stable patients (219.7±30.0pg/ml vs. 338.2±31.6pg/ml, P=0.02). In a univariate regression analysis of DMD-naïve MS patients, esRAGE serum levels inversely correlated with the rate of clinical relapse (r=-0.44, P=0.006), MS severity scale (MSSS) (r=-0.32, P=0.03), and expanded disability status scale (EDSS) (r=-0.251, P=0.07).
  
  
  CONCLUSIONS
  esRAGE serum levels are modulated by DMDs. The serum levels may be a useful biomarker of MS clinical relapse.
authors: Department of Neurology, Stroke Center, Buffalo Medical Center, Buffalo, NY, USA.
authors: Zohara
authors: Z
authors: Sternberg
authors: Department of Neurology, Baird MS Center, Buffalo Medical Center, Buffalo, NY, USA.
authors: Daniel
authors: D
authors: Sternberg
authors: Department of Neurology, Baird MS Center, Buffalo Medical Center, Buffalo, NY, USA.
authors: Allison
authors: A
authors: Drake
authors: Department of Neurology, Baird MS Center, Buffalo Medical Center, Buffalo, NY, USA.
authors: Trevor
authors: T
authors: Chichelli
authors: Department of Biostatistics, University of Buffalo, Buffalo, NY, USA.
authors: Jinhee
authors: J
authors: Yu
authors: Department of Neurology, Baird MS Center, Buffalo Medical Center, Buffalo, NY, USA.
authors: David
authors: D
authors: Hojnacki
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D000068717:Glatiramer Acetate; D017127:Glycation End Products, Advanced / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism; D016899:Interferon-beta / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D000069442:Natalizumab; D010455:Peptides / Q000627:therapeutic use; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D017127:Glycation End Products, Advanced; D007166:Immunosuppressive Agents; D058847:Inflammasomes; D000069442:Natalizumab; D010455:Peptides; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D000068717:Glatiramer Acetate; D016899:Interferon-beta
keywords: Advanced glycation end products; Clinical relapse; Endogenous secretory RAGE; Inflammation; Primary progressive; Secondary progressive