Department of Pediatrics, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
Department of Pediatric Rheumatology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Japan.
Pediatr Res. 2020 Dec;88(6):934-939. doi: 10.1038/s41390-020-0843-4. Epub 2020 Mar 17.
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.
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.
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.
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.
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.
比较托珠单抗治疗期间合并全身型幼年特发性关节炎（s-JIA）的巨噬细胞活化综合征（MAS）的血清生物标志物对 MAS 的诊断准确性。
采用酶联免疫吸附法检测 36 例 MAS 合并 s-JIA 患者（包括 12 例接受托珠单抗治疗的患者）血清中新蝶呤、IL-18、C-X-C 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 的水平。此外，比较了血清 sTNFR-II/I 比值与 MAS 临床特征的关系。
MAS 诊断时，托珠单抗治疗组所有血清细胞因子水平均显著低于未接受托珠单抗治疗组。相比之下，托珠单抗治疗组和未治疗组 MAS 诊断时的血清 sTNFR-II/I 比值无差异。ROC 曲线分析显示，sTNFR-II/I 比值的曲线下面积和截断值分别为 0.9722 和 4.71。MAS 合并 s-JIA 患者的血清 sTNFR-II/I 比值显著升高，与疾病活动度呈正相关。
这些发现表明，血清 sTNFR-II/I 比值可能是评估 s-JIA 合并 MAS 患者疾病活动度的有用指标，也是预测托珠单抗治疗患者从活动期 s-JIA 向 MAS 过渡的有用诊断标志物。
这是第一项分析托珠单抗对用于诊断 s-JIA 合并 MAS 的生物标志物血清水平的影响的研究。我们发现了托珠单抗治疗期间 s-JIA 合并 MAS 的诊断生物标志物。我们希望我们的结果可能有助于未来为接受托珠单抗治疗的患者制定新的 MAS 合并 s-JIA 诊断标准。
