ABSTRACT
Background: the receptor for advanced glycated end products [RAGE] is a multi-ligand receptor expressed as a cell surface molecule, interacting with diverse ligands. Since soluble RAGE [sRAGE] acts as a competitive receptor for cellular RAGE, the balance between these two types of receptors might be of importance in the pathogenesis of RA
Objective: to evaluate the levels of sRAGE in patients with RA compared with healthy controls and to assess the relationship between sRAGE levels and disease characteristics. Also, we assessed the association between the gene variants and the sRAGE level and disease activity
Methods: the study included 33 patients with RA and 16 healthy normal controls. All patients and controls are subjected to laboratory investigations including CBC, ESR, urine analysis, kidney function tests, liver function tests, RF and C-reactive protein [CRP]. Soluble RAGE was determined by enzymatic immunoassay and molecular study was done for single nucleotide polymorphisms [SNP] in the glycine82serine [G82S] of the RAGE gene
Results: RF was positive in 72.7% of patients and was negative in all controls. CRP was significantly higher in RA patients as compared with controls [p<0.01]. Serum levels of sRAGE were significantly lower in RA patients than controls [840.11 +/- 230.32 versus 1111.59 +/- 143.20, p<0.05]. Genotyping of the RAGE gene showed G82S in 22 out of 33 RA patients, 5 of them were homozygous for the RAGE serine82 allele, while genotyping in the control subjects showed polymorphisms in the G82S in 5 out of 16, only one of them was homozygous for the RAGE G82S allele, indicating significantly increased G82S allele in RA patients as compared with controls [p<0.05]. The G82S allele was related to the CRP and sRAGE in RA patients. The sRAGE levels were significantly lower in RA patients. Linear regression analysis detected CRP and gene polymorphism as significant predictors for sRAGE
Conclusion: the levels of sRAGE were significantly lower in patients with RA and this reduction was correlated with the disease activity and glycine82serine gene polymorphism. Thus, the sRAGE may be an important marker of disease activity and can be used as a therapeutic target in these conditions