Background Large numbers of inflammatory cytokines are considered to be complicatedly involved in rheumatoid arthritis (RA), which may be affected by unbalanced homeostasis of natural killer cells or Th1 and Th2 cells. Recently, the association with autoimmune disease and the acquired immunity system has been examined. Further, biologics that inhibit the release of proinflammatory cytokines such as those targeting tumor necrosis factor (TNF α) and interleukin-6 (IL-6), have been developed and their efficacy reported.
Objectives In this study, we measured the following items to examine the clinical usefulness in RA patients who had never received biologics: blood soluble interferon αβ-receptor (sIFN-R), IL-18, Fas Ligand (Fas-L), soluble Fas (sFas), soluble TNF-R II (sTNF-RII), C-reactive protein (CRP), IL-6, matrix metalloproteinase-3 (MMP-3), and anti-cyclic citrullinated peptide (anti-CCP) antibody.
Methods The subjects were 57 patients with RA undergoing treatment. The control group consisted of 16 patients with osteoarthritis (OA) of the knee and 216 healthy subjects. The levels of sIFN-R, IL-18, Fas-L, sFas, and sTNF-RII were measured using an enzyme-linked immunosorbent assay (ELISA). CRP and MMP-3 were measured using a clinical chemistry autoanalyzer. IL-6 and anti-CCP antibody were measured by a highly sensitive chemiluminescence immunoassay. The RA patients consisted of 11 men and 46 women, aged 31 to 85 years (mean 61.2 years). Two, 17, and 38 patients had stage II, III, and IV RA, respectively. Twenty-three, 28, and 6 patients had Class 2, 3, and 4 RA, respectively. The duration of disease was 5 to 35 years (mean 18 years). All of the RA patients in this study had been treated with oral antirheumatic drugs and had never received biologics. All of the 16 OA patients were female, aged 31 to 75 years (mean 57.1 years).
Results The levels of sIFNR (ng/ml) were 2.1±1.2, 1.4±0.7, and 1.0±0.5 in the RA, OA, and healthy subject groups, respectively; levels in the RA group were significantly higher than those in the OA and healthy subject groups (p<0.001). sIFN-R showed a positive correlation with the following: IL-18 (r =0.456), sFas (0.649), sTNF-RII (0.752), IL-6 (0.324), and CCP (0.329). There was no significant correlation with CRP (r =0.223), Fas-L (-0.202), and MMP-3 (0.193).
Conclusions In this study, the levels of sIFN-R and other biomarkers showed relatively strong positive correlation with soluble protein. Further, sIFN-R showed a low association with CRP and MMP-3, which were used to determine the therapeutic effect on RA, and a high correlation with apoptosis-related TNF and soluble Fas protein. Our results therefore suggest the involvement of cell death signal transduction from the cell membrane to intracellular components, and that there may be a long-term association with the stimulation of apoptosis-related proteins, which may lead to chronicity.
Disclosure of Interest None declared
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