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Comparative study of Interleukin-18 (IL-18) serum levels in adult onset Still’s disease (AOSD) and systemic onset juvenile idiopathic arthritis (sJIA) and its use as a biomarker for diagnosis and evaluation of disease activity
BMC Rheumatology ( IF 2.1 ) Pub Date : 2019-02-28 , DOI: 10.1186/s41927-019-0053-z
Holger Kudela 1 , Susanne Drynda 1 , Anke Lux 2 , Gerd Horneff 3, 4 , Joern Kekow 1
Affiliation  

Signs and symptoms establish the diagnosis of adult onset Still’s disease (AOSD) as well as of systemic onset juvenile idiopathic arthritis (sJIA). The published data regarding the importance of IL-18 as a marker for diagnosis and disease activity so far are conflicting. The aim of this study was to clarify the role of IL-18 as a diagnostic and disease activity marker in AOSD and sJIA. Thirty adult patients diagnosed with AOSD and twenty children diagnosed with sJIA were included in the study. Clinical and laboratory data were obtained retrospectively for each patient visit whenever IL-18 serum levels were determined. IL-18 levels were determined by ELISA. Sixty-five adults and twenty-three children presenting with fever and/or arthritis who did not meet the criteria for a diagnosis of AOSD or sJIA served as comparison groups. Rau’s criteria and CRP values were used to evaluate disease activity. IL-18 levels were significantly elevated in patients with active AOSD compared to AOSD patients in remission and to the comparison group with a median of 16,327 pg/ml, 470 pg/ml, and 368 pg/ml, respectively (p < 0.001). Analogous to AOSD in active sJIA, the median IL-18 serum level was significantly higher with 21,512 pg/ml than in the comparison group with 2580 pg/ml (p < 0.001). At our cut-off point of 5000 pg/ml, the calculated specificity of IL-18 to establish the diagnosis of AOSD was 96.9%, and the sensitivity 63.3% (AUC = 0.870, p < 0.001). For the diagnosis of sJIA, a cut-off value of 10,000 pg/ml was chosen with a specificity of 100% and a sensitivity of 60% (AUC = 0.774, p = 0.003). At a cut-off value of 5000 pg/ml, the specificity was 62% and the sensitivity 65%. This study gives further evidence to earlier publications of elevated IL-18 serum levels in active AOSD and sJIA, with up to 1000-fold higher concentrations compared to other rheumatic diseases. A clear association of IL-18 serum levels with disease activity in AOSD was found. The results support the use of IL-18 as an important biomarker in AOSD and sJIA.

中文翻译:

成人斯蒂尔病 (AOSD) 和全身性幼年特发性关节炎 (sJIA) 中白细胞介素 18 (IL-18) 血清水平的比较研究及其作为诊断和评估疾病活动性的生物标志物的应用

体征和症状确立了成人发病斯蒂尔病 (AOSD) 以及全身发病幼年特发性关节炎 (sJIA) 的诊断。迄今为止,关于 IL-18 作为诊断和疾病活动标志物重要性的已发表数据是相互矛盾的。本研究的目的是阐明 IL-18 作为 AOSD 和 sJIA 诊断和疾病活动标志物的作用。30 名诊断为 AOSD 的成人患者和 20 名诊断为 sJIA 的儿童被纳入研究。每当确定 IL-18 血清水平时,就每次患者就诊回顾性获得临床和实验室数据。IL-18水平通过ELISA确定。不符合 AOSD 或 sJIA 诊断标准的 65 名成人和 23 名出现发烧和/或关节炎的儿童作为对照组。Rau 的标准和 CRP 值用于评估疾病活动性。与处于缓解期的 AOSD 患者和对照组相比,活动性 AOSD 患者的 IL-18 水平显着升高,中位数分别为 16,327 pg/ml、470 pg/ml 和 368 pg/ml (p < 0.001)。与活动性 sJIA 中的 AOSD 类似,IL-18 血清水平中位数为 21,512 pg/ml,显着高于对照组的 2580 pg/ml (p < 0.001)。在我们 5000 pg/ml 的截止点,计算出的 IL-18 确定 AOSD 诊断的特异性为 96.9%,敏感性为 63.3%(AUC = 0.870,p < 0.001)。对于 sJIA 的诊断,选择 10,000 pg/ml 的临界值,特异性为 100%,敏感性为 60%(AUC = 0.774,p = 0.003)。在 5000 pg/ml 的临界值下,特异性为62%,敏感性为65%。这项研究进一步证明了早期发表的关于活动性 AOSD 和 sJIA 中 IL-18 血清水平升高的文献,与其他风湿性疾病相比,其浓度高达 1000 倍。发现 IL-18 血清水平与 AOSD 中的疾病活动有明显关联。该结果支持使用 IL-18 作为 AOSD 和 sJIA 的重要生物标志物。
更新日期:2019-11-28
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