Decreased level of soluble receptors of advanced glycated end products [sRAGE] and Glycine 82 Serine [G82S] polymorphism in patients with RA

ABSTRACT

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. 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. The study included 33 patients with RA and 16 healthy normal controls. All patients and controls are subjected to full clinical assessment, joint examination including tender joint count [TJC], swollen joint count [STC] and estimation of DAS 28 and 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 glycine 82 serine [G82S] of the RAGE gene. 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. RA Rheumatoid arthritis. AGEs Advanced glycation endproducts. sRAGE Soluble receptor for advanced glycation end products. NF-KB Nuclear factor-kappaB. DAS28 Disease activity score. MS Morning stiffness. TJC Tender joint count. SJC Swollen joint count. CRP C-reactive protein. SNP Single nucleotide polymorphisms. G82S Glycine 82 serine gene polymorphism. HMGB1 High mobility group box I or amphoterin. MMPs Matrix metalloproteinases. [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 serine 82 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 MS, CRP and sRAGE in RA patients. The sRAGE levels were significantly lower in RA patients with more disease activity as indicated by MS, TJC and CRP. The sRAGE levels were significantly lower in RA patients with cardiac disease than those without cardiac disease. Linear regression analysis detected CRP and gene polymorphism as significant predictors for sRAGE. The levels of sRAGE were significantly lower in patients with RA and this reduction was correlated with the disease activity and glycine 82 serine gene polymorphism. Thus, the sRAGE may be an important marker of disease activity and can be used as a therapeutic target in these conditions