Biomarkers in Pediatric Hemophagocytic Lymphohistiocytosis With Central Nervous System Involvement: A Cohort Study

Author:

Zhao Yunze1,Ou Wenxin1,Wei Ang1,Ma Honghao1,Zhang Liping1,Lian Hongyun1,Zhang Qing2,Wang Dong1,Li Zhigang2,Zhang Rui1,Wang Tianyou1

Affiliation:

1. 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

2. 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

Abstract

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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