Soluble interleukin-18 receptor complex is a novel biomarker in rheumatoid arthritis.
Soluble interleukin-18 receptor complex is a novel biomarker in rheumatoid arthritis.
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DOI：
10.1186/ar3295
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发表时间：
2011-03-24
影响因子：
4.9
通讯作者：
Aizawa H
中科院分区：
文献类型：
--
作者：
Takei S;Hoshino T;Matsunaga K;Sakazaki Y;Sawada M;Oda H;Takenaka S;Imaoka H;Kinoshita T;Honda S;Ida H;Fukuda TA;Aizawa H
白细胞介素（IL）-18受体α（IL-18 R α）的可溶性形式未见文献报道。在这项研究中，我们评估了可溶性IL-18 R α（sIL-18 R α）在类风湿关节炎（RA）患者血清中的水平和特征，并将这些结果与对照人群进行比较。用抗IL-18 R α单克隆抗体亲和柱从人血清中分离sIL-18 R α复合物。然后使用Western印迹分析检测纯化的sIL-18 R α，并用于实验中评价对IL-18应答性自然杀伤（NK）人细胞系NK 0的影响。采用酶联免疫吸附试验（ELISA）检测145例RA、6例成人Still病、31例骨关节炎（OA）、39例系统性红斑狼疮（SLE）和67例正常人血清中免疫球蛋白M、类风湿因子、抗环瓜氨酸肽抗体、白细胞介素18（IL-18）、白细胞介素13（IL-13）和干扰素γ（IFN-γ）水平。采用受试者工作特征曲线下面积（ROC-AUC）分析评价sIL-18 R α复合物的诊断效用。分离的sIL-18 R α复合物可与IL-18和可溶性形式的IL-18 R β链结合。sIL-18 R α复合物与NK 0细胞表面结合，可拮抗IL-18和IL-2对NK 0细胞的刺激作用，并抑制NK 0细胞产生IFN-γ。类风湿关节炎患者血清sIL-18 R α复合物水平的研究（186.0 ± 33.5 ng/mL，n = 145）和成人型斯蒂尔病（98.2 ± 8.9 ng/mL，n = 6），与正常对照组（52.3 ± 8.5ng/mL，n = 67）、OA组（38.6 ± 5.4ng/mL，n = 31）、SLE组（44.6 ± 3.2ng/mL，n = 39）比较，P < 0.001。RA与成人Still病患者血清sIL-18 R α复合物水平无显著性差异。RA患者血清IL-18、IL-13和IFN-γ水平显著高于OA、SLE患者和健康对照组（P < 0.01）。血清sIL-18 R α的ROC曲线下面积（AUC）分析结果表明，血清sIL-18 R α对RA的诊断有重要意义。肿瘤坏死因子抑制剂依那西普治疗6个月后，29例RA患者血清sIL-18 R α水平显著降低（P < 0.0001）。sIL-18 R α复合物可能成为诊断RA的一个潜在的生物标志物。
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. 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. 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. The sIL-18Rα complex could be a potentially useful biomarker for the diagnosis of RA.
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影响因子：
4.4
作者：
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通讯作者：
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DOI：
10.1165/rcmb.2003-0306oc
发表时间：
2004-12-01
影响因子：
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影响因子：
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DOI：
10.1164/rccm.200603-316oc
发表时间：
2007-07-01
影响因子：
24.7
作者：
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