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In this study, we evaluated the levels and characteristics of soluble IL-18R\u03b1 (sIL-18R\u03b1) in the sera of patients with rheumatoid arthritis (RA) and compared these results to control populations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The sIL-18R\u03b1 complex was isolated from pooled human blood serum using an anti-IL-18R\u03b1 monoclonal antibody affinity column. The purified sIL-18R\u03b1 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)-\u03b3. Area under the receiver operating characteristic curve (ROC-AUC) analysis was used to evaluate the diagnostic utility of the sIL-18R\u03b1 complex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The isolated sIL-18R\u03b1 complex can be associated with IL-18 and the soluble form of the IL-18R\u03b2 chain. The sIL-18R\u03b1 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-\u03b3 production by the cells. The serum levels of sIL-18R\u03b1 complex in RA (186.0 \u00b1 33.5 ng\/mL,<jats:italic>n<\/jats:italic>= 145) and adult-onset Still's disease (98.2 \u00b1 8.9 ng\/mL,<jats:italic>n<\/jats:italic>= 6) were significantly (<jats:italic>P<\/jats:italic>&lt; 0.001) higher than those in the healthy controls (52.3 \u00b1 8.5 ng\/mL,<jats:italic>n<\/jats:italic>= 67), OA (38.6 \u00b1 5.4 ng\/mL,<jats:italic>n<\/jats:italic>= 31), SLE (44.6 \u00b1 3.2 ng\/mL,<jats:italic>n<\/jats:italic>= 39). The serum level of sIL-18R\u03b1 complex was not significantly different between RA and adult-onset Still's disease patients. The serum levels of IL-18, IL-13 and IFN-\u03b3 in the RA patients were significantly (<jats:italic>P<\/jats:italic>&lt; 0.01) higher than in OA and SLE patients as well as healthy controls. ROC-AUC analysis of the serum concentration of sIL-18R\u03b1 indicated that it was significantly diagnostic of RA. Moreover, a tumor necrosis factor inhibitor, etanercept, significantly (<jats:italic>P<\/jats:italic>&lt; 0.0001) decreased levels of sIL-18R\u03b1 in the sera of 29 RA patients 6 months after treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The sIL-18R\u03b1 complex could be a potentially useful biomarker for the diagnosis of RA.<\/jats:p><\/jats:sec>","DOI":"10.1186\/ar3295","type":"journal-article","created":{"date-parts":[[2011,4,1]],"date-time":"2011-04-01T16:29:37Z","timestamp":1301675377000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Soluble interleukin-18 receptor complex is a novel biomarker in rheumatoid arthritis"],"prefix":"10.1186","volume":"13","author":[{"given":"Satoko","family":"Takei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Hoshino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuko","family":"Matsunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Sakazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Sawada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanako","family":"Oda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ichi","family":"Takenaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruki","family":"Imaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kinoshita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiyo","family":"Honda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Ida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taka-aki","family":"Fukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisamichi","family":"Aizawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2011,3,24]]},"reference":[{"key":"9745_CR1","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/S0952-7915(01)00306-5","volume":"14","author":"JE Sims","year":"2002","unstructured":"Sims JE: IL-1 and IL-18 receptors, and their extended family. 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