TNF-related apoptosis-inducing ligand levels in rheumatoid arthritis, osteoarthritis, and spondyloarthritis

Abstract

Abstract Introduction Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a tumor necrosis factor (TNF) family member capable of inducing apoptosis in many cell types. Data suggest that TRAIL/TRAIL receptor expression profiles on Tcells might be important in rheumatoid arthritis (RA) pathogenesis. Objectives To characterize the role of TNF-related apoptosis-inducing ligand (TRAIL) in rheumatoid arthritis (RA) and to explore whether TRAIL investigated in serum and synovial fluid were associated with clinical, laboratory, and radiological variables of RA disease activity and severity. Methods Circulating levels of TRAIL were measured by ELISA in serum samples obtained from 50 patients with RA (during activity and quiescence), 20 patients with osteoarthritis, 15 patients with spondyloarthritis, and 50 normal healthy individuals serving as controls. Results The median serum TRAIL concentrations were increasingly higher across the following groups: healthy controls (185pg/ml), and RA patients with active disease (1625 pg/ml; P=0.0001 vs. controls) and inactive disease (1750 pg/ml; P=0.0001 vs. controls) (inactive vs. active RA; P = 0.07). It is noteworthy that RA patients had significant higher median TRAIL concentrations as compared with osteoarthritis patients whether during activity or during quiescence. However, the median levels of TRAIL were statistically comparable in RA and spondyloarthritis patients. The median and mean ± SD synovial fluid TRAIL concentrations were 2100 and 1765.8 ± 752 pg/ml, respectively. The levels of TRAIL in synovial fluid from the patients were higher than those in sera from both the patients and the healthy individuals. TRAIL concentrations in paired sera and synovial fluid samples could be related to each other. Serum and synovial concentrations of TRAIL were correlated positively with the total number of joints with active arthritis and with the overall articular severity score. Patients with Larsen index and total radiographic score of at least 1 had significantly higher serum TRAIL levels than patients with indices and scores 1 or less. Conclusion Upregulated expression of TRAIL might be somewhat useful for the evaluation of RA disease activity and progression, although its increment is not disease specific.