title: Association of plasma sRAGE, but not esRAGE with lung function impairment in COPD.
abstract: BACKGROUND
  Plasma soluble Receptor for Advanced Glycation End Product (sRAGE) is considered as a biomarker in COPD. The contribution of endogenous sRAGE (esRAGE) to the pool of plasma sRAGE and the implication of both markers in COPD pathogenesis is however not clear yet. The aim of the current study was therefore to measure plasma levels of esRAGE comparative to total sRAGE in patients with COPD and a control group. Further, we established the relations of esRAGE and total sRAGE with disease specific characteristics such as lung function and DLCO, and with different circulating AGEs.
  
  
  METHODS
  Plasma levels of esRAGE and sRAGE were measured in an 88 patients with COPD and in 55 healthy controls. FEV1 (%predicted) and FEV1/VC (%) were measured in both groups; DLCO (%predicted) was measured in patients only. In this study population we previously reported that the AGE Nϵ-(carboxymethyl) lysine (CML) was decreased, Nϵ-(carboxyethyl) lysine (CEL) increased and pentosidine was not different in plasma of COPD patients compared to controls.
  
  
  RESULTS
  Plasma esRAGE (COPD: 533.9 ± 412.4, CONTROLS: 848.7 ± 690.3 pg/ml; p = 0.000) was decreased in COPD compared to controls. No significant correlations were observed between plasma esRAGE levels and lung function parameters or plasma AGEs. A positive correlation was present between esRAGE and total sRAGE levels in the circulation. Confirming previous findings, total sRAGE (COPD: 512.6 ± 403.8, CONTROLS: 1834 ± 804.2 pg/ml; p < 0.001) was lower in patients compared to controls and was positively correlated FEV1 (r = 0.235, p = 0.032), FEV1/VC (r = 0.218, p = 0.047), and DLCO (r = 0.308, p = 0.006). sRAGE furthermore did show a significant positive association with CML (r = 0.321, p = 0.003).
  
  
  CONCLUSIONS
  Although plasma esRAGE is decreased in COPD patients compared to controls, only total sRAGE showed a significant and independent association with FEV1, FEV1/VC and DLCO, indicating that total sRAGE but not esRAGE may serve as marker of COPD disease state and severity.
authors.forename: Poornima
authors.initials: P
authors.lastname: Gopal
authors.forename: Niki L
authors.initials: NL
authors.lastname: Reynaert
authors.forename: Jean L J M
authors.initials: JL
authors.lastname: Scheijen
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.forename: Frits M E
authors.initials: FM
authors.lastname: Franssen
authors.forename: Emiel F M
authors.initials: EF
authors.lastname: Wouters
authors.affiliation: Centre of expertise for chronic organ failure (Ciro+), PO Box 4080, Horn, the Netherlands. ericarutten@ciro-horn.nl.
authors.forename: Erica P A
authors.initials: EP
authors.lastname: Rutten
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000175:diagnosis*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*
chemical_list: D015415:Biomarkers; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic