Soluble receptors for tumor necrosis factor and interleukin-2 in serum and synovial fluid of patients with rheumatoid arthritis, reactive arthritis and osteoarthritis

Abstract

Objective: To compare levels of soluble tumor necrosis factor receptor (TNF-R) and soluble interleukin 2 receptor (sIL-2R) in sera and synovial fluids (SF) of patients with rheumatoid arthritis (RA), reactive arthritis (ReA), and osteoarthritis (OA) in order to investigate the usefulness of soluble cytokine receptors for differentiation diagnosis and their involvement in the pathophysiology of rheumatic diseases.

Methods: Soluble TNF-R (55 kDa), sIL-2R, and TNF-alpha were measured by ELISA in sera and SF of patients with RA, ReA, and OA and correlated with serological and clinical disease activity variables.

Results: Serum TNF-R was significantly (p < 0.0001) elevated in RA (4.6 +/- 2.1 ng/ml, mean +/- SD) compared to ReA (2.5 +/- 0.6 ng/ml), OA (2.2 +/- 0.7 ng/ml), and healthy controls (2.0 +/- 0.4 ng/ml). In SF mean TNF-R levels were 21 +/- 9.3 ng/ml in RA, 12.5 +/- 5.1 ng/ml in ReA, and 8.7 +/- 3.7 ng/ml in OA (p < 0.0001 for RA vs ReA or OA; p < 0.02 for ReA vs OA). SF levels were significantly higher in rheumatoid factor (RF) positive than in RF negative patients with RA. In patients with RA, correlations were found between TNF-R and TNF-alpha in SF (r = 0.32, p < 0.01), and between TNF-R and early morning stiffness (r = 0.4, p < 0.003 in serum; r = 0.29, p < 0.05 in SF). However, there was no correlation with disease activity variables such as Ritchie index, erythrocyte sedimentation rate (ESR) or C-reactive protein. Serum levels of IL-2R were elevated in RA and ReA, but a significant difference was found only for RA versus OA and controls (p < 0.0005), whereas in SF significant differences existed between all 3 patient groups (RA/ReA: p < 0.004; RA/OA: p < 0.0001; ReA/OA: p < 0.0003); both in serum and SF, levels of RF positive patients with RA were higher than those of RF negative patients. In patients with RA, IL-2R correlated weakly with ESR (r = 0.24, p < 0.05), iron concentration (r = -0.35, p < 0.005), and CRP (r = 0.24, p < 0.05).

Conclusion: In RA, in contrast to ReA and OA, TNF-R and IL-2R were not only elevated in the joint fluid but also in serum. This indicates general activation of the immune system in RA, but not in ReA and OA. Therefore the soluble receptors, especially TNF-R, might become useful diagnostic variables to distinguish RA from ReA and OA.