Soluble interleukin-18 receptor complex is a novel biomarker in rheumatoid arthritis

Soluble interleukin-18 receptor complex is a novel biomarker in rheumatoid arthritis,10.1186/ar3295,Arthritis Research & Therapy,Satoko Takei,Tomoaki

Soluble interleukin-18 receptor complex is a novel biomarker in rheumatoid arthritis   (Citations: 1)
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Satoko Takei, Tomoaki Hoshino, Kazuko Matsunaga, Yuki Sakazaki, Masanori Sawada, Hanako Oda, Shin-ichi Takenaka, Haruki Imaoka, Takashi Kinoshita, Seiyo Honda, Hiroaki Ida, Taka-aki Fukuda
Introduction  There has been no report in the literature of a soluble form of interleukin (IL)-18 receptor α (IL-18Rα). In this study, we evaluated the levels and characteristics of soluble IL-18Rα (sIL-18Rα) in the sera of patients with rheumatoid arthritis (RA) and compared these results to control populations. Methods   The sIL-18Rα complex was isolated from pooled human blood serum using an anti-IL-18Rα monoclonal antibody affinity column. The purified sIL-18Rα was then examined using Western blot analysis and used in experiments to evaluate the effects on an IL-18-responsive natural killer (NK) human cell line, NK0. An enzyme-linked immunosorbent assay was developed, and sera from 145 patients with RA, 6 patients with adult-onset Still's disease, 31 patients with osteoarthritis (OA), 39 patients with systemic lupus erythematosus (SLE) and 67 controls were tested, along with levels of immunoglobulin M, rheumatoid factor, anticyclic citrullinated peptide antibody, IL-18, IL-13 and interferon (IFN)-γ. Area under the receiver operating characteristic curve (ROC-AUC) analysis was used to evaluate the diagnostic utility of the sIL-18Rα complex. Results  The isolated sIL-18Rα complex can be associated with IL-18 and the soluble form of the IL-18Rβ chain. The sIL-18Rα complex bound to the surface to the NK0 cell line, antagonized the stimulatory effects of IL-18 and IL-2 on the NK0 cell line and inhibited IFN-γ production by the cells. The serum levels of sIL-18Rα complex in RA (186.0 ± 33.5 ng/mL, n = 145) and adult-onset Still's disease (98.2 ± 8.9 ng/mL, n = 6) were significantly (P n = 67), OA (38.6 ± 5.4 ng/mL, n = 31), SLE (44.6 ± 3.2 ng/mL, n = 39). The serum level of sIL-18Rα complex was not significantly different between RA and adult-onset Still's disease patients. The serum levels of IL-18, IL-13 and IFN-γ in the RA patients were significantly (P < 0.01) higher than in OA and SLE patients as well as healthy controls. ROC-AUC analysis of the serum concentration of sIL-18Rα indicated that it was significantly diagnostic of RA. Moreover, a tumor necrosis factor inhibitor, etanercept, significantly (P < 0.0001) decreased levels of sIL-18Rα in the sera of 29 RA patients 6 months after treatment. Conclusions  The sIL-18Rα complex could be a potentially useful biomarker for the diagnosis of RA.
Journal: Arthritis Research & Therapy - ARTHRITIS RES THER , vol. 13, no. 2, pp. 1-13, 2011
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    • ...Th e study of Satoko Takei and colleagues [1] in this issue of Arthritis Research & Th erapy describes a new serum biomarker with clear potential of becoming a valuable tool for the pharmaco diagnosis of RA. Biomarker tests that are currently available are failing to guide therapeutic decision making...
    • ...Th e study of Takei and colleagues [1] demonstrates that the systemic soluble IL-18Rα complex, which in vitro exhibits antagonistic activity, probably also contains a dimeric IL-18 protein and the soluble form of the IL-18Rβ chain...

    Fons AJ van de Loo. Soluble IL18 receptor complex: a new star in the firmament of rheumato...

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