伴有中枢神经系统受累的儿童噬血细胞性淋巴组织细胞增生症中的生物标志物：一项队列研究。
Biomarkers in Pediatric Hemophagocytic Lymphohistiocytosis With Central Nervous System Involvement: A Cohort Study.
机构信息
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.
出版信息
J Pediatr Hematol Oncol. 2024 Oct 1;46(7):364-372. doi: 10.1097/MPH.0000000000002937. Epub 2024 Aug 15.
BACKGROUND
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).
METHODS
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.
RESULTS
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).
CONCLUSIONS
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.
背景
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。
方法
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。
结果
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）。
结论
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。
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