Increased pentosidine, an advanced glycation end product, in plasma and synovial fluid from patients with rheumatoid arthritis and its relation with inflammatory markers

Pentosidine is an advanced glycation end product (AGE) formed by combined processes of glycation and oxidation (glycoxidation) between carbohydrate-derived carbonyl group and protein amino group. Recent studies demonstrated the increased pentosidine levels not only in diabetic patients with hyperglycemia but also in normoglycemic uremic patients due to increased oxidative stress. Rheumatoid arthritis (RA) is a state of increased oxidative stress associated with chronic inflammation. This suggested an enhanced glycoxidation reaction and increased AGE levels in RA patients. In the present study, we therefore determined, by high performance liquid chromatographic (HPLC) assay, the concentrations of pentosidine in plasma and synovial fluid from 22 patients with rheumatoid arthritis (RA) and compared their levels with those in 17 patients with osteoarthritis (OA), 26 diabetic patients, and 25 normal subjects. The levels of inflammatory markers and markers of tissue destruction, metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), were also measured in the same samples. Pentosidine levels in plasma and synovial fluid from RA patients were significantly higher than those in OA patients, diabetic patients, and normal subjects. There was a significant correlation between the pentosidine levels in plasma and those in synovial fluid. Among markers of inflammation and matrix destruction, pentosidine levels in plasma from RA patients were correlated with the levels of C-reactive protein (CRP), erythrocyte sedimentation rate, white blood cell count, and platelet count. Multiple stepwise regression analysis reveals an independent influence of CRP on plasma pentosidine levels. In conclusion, pentosidine levels are significantly higher in plasma and synovial fluid from RA patients and may be useful as a biomarker of chronic inflammation in RA patients.