title: Soluble interleukin-18 receptor complex is a novel biomarker in rheumatoid arthritis.
abstract: BACKGROUND
  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 < 0.001) higher than those in the healthy controls (52.3 ± 8.5 ng/mL, 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.
authors: Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.
authors: Satoko
authors: S
authors: Takei
authors: Tomoaki
authors: T
authors: Hoshino
authors: Kazuko
authors: K
authors: Matsunaga
authors: Yuki
authors: Y
authors: Sakazaki
authors: Masanori
authors: M
authors: Sawada
authors: Hanako
authors: H
authors: Oda
authors: Shin-ichi
authors: S
authors: Takenaka
authors: Haruki
authors: H
authors: Imaoka
authors: Takashi
authors: T
authors: Kinoshita
authors: Seiyo
authors: S
authors: Honda
authors: Hiroaki
authors: H
authors: Ida
authors: Taka-aki
authors: TA
authors: Fukuda
authors: Hisamichi
authors: H
authors: Aizawa
mesh_terms: D000368:Aged; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000097:blood*; D015415:Biomarkers / Q000032:analysis* / Q000378:metabolism; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D053724:Receptors, Interleukin-18 / Q000097:blood*; D012680:Sensitivity and Specificity; D012995:Solubility
chemical_list: D015415:Biomarkers; D053724:Receptors, Interleukin-18