soluble interleukin-18 receptor complex is a novel biomarker in rheumatoid arthritis可溶性受体interleukin-18复杂类风湿性关节炎是一种新型的生物标志物.pdf

Takei et al. Arthritis Research Therapy 2011, 13:R52 /content/13/2/R52 RESEARCH ARTICLE Open Access Soluble interleukin-18 receptor complex is a novel biomarker in rheumatoid arthritis * 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 and Hisamichi Aizawa Abstract Introduction: There has been no report in the literature of a soluble form of interleukin (IL)-18 receptor a (IL-18Ra). In this study, we evaluated the levels and characteristics of soluble IL-18Ra (sIL-18Ra) in the sera of patients with rheumatoid arthritis (RA) and compared these results to control populations. Methods: The sIL-18Ra complex was isolated from pooled human blood serum using an anti-IL-18Ra monoclonal antibody affinity column. The purified sIL-18Ra 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)-g. Area under the receiver operating characteristic curve (ROC-AUC) analysis was used to evaluate the diagnostic utility of the sIL-18Ra complex. Results: The isolated sIL-18Ra complex can be associated with IL-18 and the soluble form of the IL-18Rb chain. The sIL- 18Ra complex bound to the surface to the NK0 cell line, antagonized the stimulatory effects of IL-18 and IL-2