title: Soluble form of receptor for advanced glycation end-products (sRAGE): do sRAGE ligands or anti-sRAGE auto-antibodies interfere with sRAGE quantification?
abstract: BACKGROUND
  The soluble form of the receptor for advanced glycation end-products (sRAGE) has been studied in various diseases. It is not clear why sRAGE levels vary between studies, with controversial results. What also remains to be determined is whether receptor for advanced glycation end-products (RAGE) ligands could affect sRAGE assessment by epitope masking. Recently described anti-sRAGE autoantibodies may play an interfering role. The aim of this study was therefore to investigate the influence of RAGE ligands and anti-sRAGE autoantibodies on sRAGE quantification.
  
  
  METHODS
  The RAGE ligands carboxymethyllysine (CML; AGEs with a high affinity for RAGE), S100 proteins, high-mobility group protein B1 (HMGB1) and β-amyloid peptide (aβ) were tested by enzyme-linked immunosorbent assay (ELISA) with recombinant sRAGE (rHu-sRAGE) or serum from healthy controls. Using ELISA, anti-sRAGE autoantibodies (IgGs) were identified in haemodialysis (HD) patients, then purified and incubated with rHu-sRAGE or serum to investigate their effects on sRAGE levels.
  
  
  RESULTS
  RAGE ligands, either alone at three different concentrations (CML was also tested at different glycation levels) or a mixture of all these ligands, did not affect sRAGE levels when incubated with rHu-sRAGE or control serum. Compared with healthy controls, HD patients had higher levels of sRAGE (P < 0.001) and anti-sRAGE IgGs (P < 0.05). However, incubation of rHu-sRAGE with purified IgGs from HD patients had no effect on sRAGE quantification.
  
  
  CONCLUSIONS
  RAGE ligands or anti-sRAGE autoantibodies did not interfere with sRAGE quantification. Further studies are required to elucidate the variability in sRAGE levels reported in the literature and to define the potential of sRAGE for use as a reliable biomarker.
authors: Department of Vascular Aging Biology, Blood-Vessel Interface and Vascular Repair Unit, Lille School of Medicine, Lille2 University, Lille, France.
authors: Rodrigo
authors: R
authors: Lorenzi
authors: Nicolas
authors: N
authors: Grossin
authors: Marc
authors: M
authors: Lambert
authors: Maité
authors: M
authors: Daroux
authors: Zoubir
authors: Z
authors: Adjoutah
authors: Christophe
authors: C
authors: Flahaut
authors: Philippe
authors: P
authors: Jacolot
authors: Frédéric J
authors: FJ
authors: Tessier
authors: Didier
authors: D
authors: Lefranc
authors: Pierre
authors: P
authors: Desremaux
authors: Sylvain
authors: S
authors: Dubucquoi
authors: Eric
authors: E
authors: Boulanger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016477:Artifacts; D001323:Autoantibodies / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008024:Ligands; D008297:Male; D008875:Middle Aged; D017434:Protein Structure, Tertiary; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000032:analysis* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006435:Renal Dialysis; D012995:Solubility
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D008024:Ligands; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic
keywords: Quality assurance & control; clinical studies; immunoassay; laboratory methods