Comparison of serum cytokine profiles in macrophage activation syndrome complicating different background rheumatic diseases in children

Comparison of serum cytokine profiles in macrophage activation syndrome complicating different background rheumatic diseases in children
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DOI:
10.1093/rheumatology/keaa299
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发表时间:
2021-01-01
期刊:
影响因子:
5.5
通讯作者:
Yachie, Akihiro
Yachie, Akihiro
中科院分区:
医学1区
文献类型:
--
作者:
Mizuta, Mao;Shimizu, Masaki;Yachie, Akihiro

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目标。比较不同背景风湿性疾病中巨噬细胞激活综合征(MAS)发生发展过程中的细胞因子,寻找诊断MAS的血清生物标志物。采用双抗体夹心法测定12例SLE、12例JDM、75例川崎病(KD)、179例系统性JIA(S-JIA)患者血清新喋呤、IL-6、IL-18及sTNFR-I、sTNFR-II水平。将这些结果与MAS的临床特征进行比较。所有疾病患者MAS期血清新喋呤、IL-18和sTNFR-II水平均显著高于活动期。此外,系统性红斑狼疮、川崎病和S甲亢患者MAS期血清sTNFR-I水平显著高于活动期。受试者工作特征(ROC)曲线分析显示,SLE患者血清sTNFR-I水平、JDM患者血清IL-18水平、KD和S甲患者血清sTNFR-II水平在ROC曲线下最高。血清细胞因子水平与血清铁蛋白水平呈显著正相关。干扰素-γ、IL-18和肿瘤坏死因子-α的过度产生可能与MAS的发生发展密切相关。SLE患者sTNFR-I、JDM患者IL-18、KD和S-JIA患者血清sTNFR-II水平可作为活动期向MAS转变的诊断指标。
Objectives. To compare the cytokines involved in the development of macrophage activation syndrome (MAS) in different background rheumatic diseases and to identify serum biomarkers for MAS diagnosis.Methods. Serum neopterin, IL-6, IL-18 and soluble TNF receptor (sTNFR) type I (sTNFR-I) and type II (sTNFR-II) levels were determined using ELISA in 12 patients with SLE, including five with MAS; 12 patients with JDM, including four with MAS; 75 patients with Kawasaki disease (KD), including six with MAS; and 179 patients with systemic JIA (s-JIA), including 43 with MAS. These results were compared with the clinical features of MAS.Results. Serum neopterin, IL-18 and sTNFR-II levels were significantly higher during the MAS phase than during the active phase in patients with all diseases. Furthermore, serum sTNFR-I levels were significantly higher during the MAS phase than during the active phase in patients with SLE, KD and s-JIA. Receiver operating characteristic (ROC) curve analysis revealed that serum sTNFR-I levels for SLE, serum IL-18 levels for JDM, and serum sTNFR-II levels for KD and s-JIA had the highest areas under the ROC curve. Serum levels of these cytokines were significantly and positively correlated with serum ferritin levels.Conclusions. Overproduction of IFN-gamma, IL-18 and TNF-alpha might be closely related to the development of MAS. Serum levels of sTNFR-I for SLE, IL-18 for JDM, and sTNFR-II for KD and s-JIA might be useful diagnostic markers for the transition from active phase to MAS.