Association of plasma sRAGE, but not esRAGE with lung function impairment in COPD

RATIONALE: 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 D(L)CO, 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. FEV(1) (%predicted) and FEV(1)/VC (%) were measured in both groups; D(L)CO (%predicted) was measured in patients only. In this study population we previously reported that the AGE N(ϵ)-(carboxymethyl) lysine (CML) was decreased, N(ϵ)-(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 FEV(1) (r = 0.235, p = 0.032), FEV(1)/VC (r = 0.218, p = 0.047), and D(L)CO (r = 0.308, p = 0.006). sRAGE furthermore did show a significant positive association with CML (r = 0.321, p = 0.003). CONCLUSION: Although plasma esRAGE is decreased in COPD patients compared to controls, only total sRAGE showed a significant and independent association with FEV(1), FEV(1)/VC and D(L)CO, indicating that total sRAGE but not esRAGE may serve as marker of COPD disease state and severity.