Background To compare the accuracy of serum biomarkers for the diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA) during tocilizumab therapy. Methods Serum cytokine levels of neopterin, IL-18, C-X-C motif chemokine ligand 9, soluble tumor necrosis factor receptor (sTNFR)-I, and sTNFR-II were determined by enzyme-linked immunosorbent assay in 36 patients with MAS complicating s-JIA including 12 patients receiving tocilizumab. Furthermore, the serum sTNFR-II/I ratio was compared with the clinical features of MAS. Results The levels of all serum cytokines at MAS diagnosis were significantly lower in the tocilizumab-treated group than in the tocilizumab-untreated group. In contrast, the serum sTNFR-II/I ratio at MAS diagnosis was comparable between the tocilizumab-treated and the tocilizumab-untreated groups. The receiver operating characteristic curve analysis revealed that the area under the curve and cut-off values of sTNFR-II/I ratio were 0.9722 and 4.71, respectively. The serum sTNFR-II/I ratio, which was significantly elevated in patients with MAS complicating s-JIA, was correlated positively with disease activity. Conclusions These findings suggest that the serum sTNFR-II/I ratio might be a useful indicator to evaluate disease activity in MAS complicating s-JIA and a useful diagnostic marker for the transition from active-phase s-JIA to MAS even in tocilizumab-treated patients. Impact This is the first study to analyze the role of tocilizumab in modifying the serum levels of biomarkers used for the diagnosis of MAS complicating s-JIA. We found the biomarker for the diagnosis of MAS complicating s-JIA during tocilizumab therapy. We hope our results might be useful for the development of a new criteria for the diagnosis of MAS complicating s-JIA in patients treated with tocilizumab in future.

中文翻译：

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托珠单抗治疗期间巨噬细胞活化综合征并发全身性幼年特发性关节炎的血清生物标志物的比较

背景 比较血清生物标志物在托珠单抗治疗期间诊断巨噬细胞活化综合征 (MAS) 并发全身性幼年特发性关节炎 (s-JIA) 的准确性。方法 采用酶联免疫吸附法测定 36 例 MAS 合并 s-JIA 患者血清中新蝶呤、IL-18、CXC 基序趋化因子配体 9、可溶性肿瘤坏死因子受体 (sTNFR)-I 和 sTNFR-II 的血清细胞因子水平，包括12 名患者接受托珠单抗治疗。此外，将血清 sTNFR-II/I 比值与 MAS 的临床特征进行比较。结果 MAS 诊断时所有血清细胞因子水平在托珠单抗治疗组中显着低于托珠单抗未治疗组。相比之下，MAS 诊断时的血清 sTNFR-II/I 比率在托珠单抗治疗组和托珠单抗未治疗组之间具有可比性。受试者工作特征曲线分析显示，sTNFR-II/I 比值的曲线下面积和临界值分别为 0.9722 和 4.71。血清 sTNFR-II/I 比值在 MAS 并发 s-JIA 患者中显着升高，与疾病活动度呈正相关。结论 这些发现表明，血清 sTNFR-II/I 比值可能是评估 MAS 并发 s-JIA 的疾病活动性的有用指标，也是从活动期 s-JIA 过渡到 MAS 的有用诊断标志，即使在托珠单抗治疗中耐心。影响 这是第一项分析托珠单抗在改变用于诊断 MAS 并发 s-JIA 的生物标志物血清水平中的作用的研究。我们发现了在托珠单抗治疗期间诊断 MAS 并发 s-JIA 的生物标志物。我们希望我们的结果可能有助于制定新的标准，用于未来在接受托珠单抗治疗的患者中诊断 MAS 并发 s-JIA。