Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Disease in Children, Ministry of Education; Beijing Children's Hospital, Capital Medical University, National Center for Children's Health.
Hematologic Disease Laboratory, Beijing Pediatric Research Institute; Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Disease in Children, Ministry of Education; Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, P.R. China.
J Pediatr Hematol Oncol. 2024 Oct 1;46(7):364-372. doi: 10.1097/MPH.0000000000002937. Epub 2024 Aug 15.
The aim of this study was to analyze the clinical significance of cerebrospinal fluid (CSF) cytokines in hemophagocytic lymphohistiocytosis associated with central nervous system (CNS-HLH).
CSF cytokine levels, including interferon (IFN)-γ, soluble CD25 (sCD25), interleukin (IL)-6, IL-10, IL-18, and CXCL9 were measured at disease onset and during the treatment. Five newly diagnosed patients with demyelination disease were enrolled for comparison.
Sixty-five samples from 36 patients (13 in the CNS group and 23 in the non-CNS group) were detected. Levels of CSF IFN-γ, sCD25, IL-10, IL-18, and CXCL9 in the CNS group were higher than those in the non-CNS group ( P =0.038, <0.001, <0.001, 0.005, and <0.001), and levels of CSF sCD25, IL-10, IL-18, and CXCL9 in the CNS group were higher than those in the demyelination group ( P =0.001, 0.008, 0.004, and 0.003). There was no significant difference in IL-6 levels among the 3 groups ( P =0.339). CSF IFN-γ, sCD25, IL-10, IL-18, and CXCL9 could assist in diagnosing CNS-HLH. The diagnostic efficiency of CSF sCD25, IL-10, and CXCL9 was better, with a cutoff value of 154.64, 1.655, and 19.54 pg/mL, respectively. The area under the curve was >0.9, with sensitivity and specificity >80%. Correlation analysis suggested that in the CNS group, IFN-γ levels in CSF and serum correlated positively ( R =0.459, P =0.007), while there was no correlation between CSF CXCL9 and serum IFN-γ ( P =0.915).
CSF IFN-γ, sCD25, IL-10, IL-18, and CXCL9 levels were significantly higher in HLH patients with CNS involvement than those without and could predict HLH patients with CNS involvement. CSF CXCL9 might be a more sensitive biomarker to CNS-HLH than IFN-γ, while CSF IL-6 does not seem to play a vital role.
本研究旨在分析与中枢神经系统（CNS）相关的噬血细胞性淋巴组织细胞增多症（HLH）患者脑脊液（CSF）细胞因子的临床意义。
在疾病发病时和治疗期间测量 CSF 细胞因子水平，包括干扰素（IFN）-γ、可溶性 CD25（sCD25）、白细胞介素（IL）-6、IL-10、IL-18 和 CXCL9。纳入 5 例新诊断的脱髓鞘疾病患者作为对照。
共检测了 36 例患者的 65 个样本（CNS 组 13 例，非 CNS 组 23 例）。CNS 组 CSF IFN-γ、sCD25、IL-10、IL-18 和 CXCL9 水平均高于非 CNS 组（P=0.038、<0.001、<0.001、0.005 和 <0.001），且 CSF sCD25、IL-10、IL-18 和 CXCL9 水平均高于脱髓鞘组（P=0.001、0.008、0.004 和 0.003）。三组间 IL-6 水平无显著差异（P=0.339）。CSF IFN-γ、sCD25、IL-10、IL-18 和 CXCL9 有助于诊断 CNS-HLH。CSF sCD25、IL-10 和 CXCL9 的诊断效率更高，截断值分别为 154.64、1.655 和 19.54pg/mL，曲线下面积均>0.9，灵敏度和特异性均>80%。相关性分析提示，在 CNS 组中，CSF 和血清中 IFN-γ水平呈正相关（R=0.459，P=0.007），而 CSF CXCL9 与血清 IFN-γ无相关性（P=0.915）。
与无中枢神经系统受累的 HLH 患者相比，中枢神经系统受累的 HLH 患者 CSF IFN-γ、sCD25、IL-10、IL-18 和 CXCL9 水平显著升高，可预测中枢神经系统受累的 HLH 患者。CSF CXCL9 可能是比 IFN-γ更敏感的中枢神经系统 HLH 生物标志物，而 CSF IL-6 似乎在其中不起关键作用。
