Decreased soluble RAGE in neutrophilic asthma is correlated with disease severity and RAGE G82S variants

Abstract

The advanced glycosylation end product-specific receptor (RAGE) has been demonstrated to be an important mediator of asthma pathogenesis. The soluble isoform of RAGE (sRAGE) acts as a decoy' to sequester RAGE ligands, and thus prevents their binding to the receptor. A number of reports have linked deficiency of sRAGE to the severity and outcomes of various human diseases, and association with RAGE G82S variants. However, whether sRAGE levels are increased or decreased in asthmatic patients is unclear. The aim of the present study was to determine plasma sRAGE levels in different asthma phenotypes and associations of plasma sRAGE levels with RAGE G82S variants. A total of 85 neutrophilic and 109 non-neutrophilic newly diagnosed asthmatic patients, and 118 healthy controls, were recruited. Plasma sRAGE levels were measured by ELISA analysis. RAGE G82S genotypes were detected using the Sanger sequencing method. Plasma sRAGE levels were decreased in neutrophilic asthmatics (443.67 +/- 208.9 pg/ml) and increased in non-neutrophilic asthmatics (677.63 +/- 300.75 pg/ml) compared with healthy controls (550.02 +/- 300.83 pg/ml) (P<0.001). Plasma sRAGE levels were positively correlated with FEV1% predicted (FEV1% Pre) (r(p)=0.258; P=0.023) in neutrophilic asthmatics. The frequency of G82S genotypes was significantly different between neutrophilic and non-neutrophilic asthmatics (P=0.009). Neutrophilic asthmatics with genotypes A/G or A/A (389.83 +/- 150.37 and 264.59 +/- 161.74 pg/ml, respectively) had significantly decreased sRAGE levels compared with the G/G genotype (498.64 +/- 235.37 pg/ml) (P=0.022). Those with the A/G and A/A genotype (60.14 +/- 22.36%) displayed a trend toward lower FEV1% Pre compared with those with the G/G genotype (64.51 +/- 27.37%). No significant difference in sRAGE levels or an association with FEV1% Pre was observed between the different genotypes in non-neutrophilic asthmatics. In conclusion, the results of the present study indicated that plasma sRAGE levels are altered in different asthma inflammatory phenotypes. Plasma sRAGE may be a biomarker of asthma severity and may be associated with G82S gene variants in neutrophilic asthmatics.