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

Area of Science:

• Neuroimmunology
• Hematology
• Clinical Diagnostics

Background:

• Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome.
• Central nervous system involvement (CNS-HLH) significantly worsens prognosis and presents diagnostic challenges.
• Understanding the role of cerebrospinal fluid (CSF) cytokines is crucial for diagnosing and managing CNS-HLH.

Purpose of the Study:

• To investigate the clinical significance of CSF cytokines in patients with CNS-HLH.
• To identify specific CSF cytokine profiles that differentiate CNS-HLH from non-CNS HLH and other neurological conditions.
• To evaluate the diagnostic utility of CSF cytokines for CNS-HLH.

Main Methods:

• Measurement of CSF cytokine levels, including IFN-γ, sCD25, IL-6, IL-10, IL-18, and CXCL9, at disease onset and during treatment.
• Comparison of cytokine levels between patients with CNS-HLH, non-CNS HLH, and a control group with demyelination disease.
• Statistical analysis to determine significant differences and diagnostic efficiency (sensitivity, specificity, area under the curve).

Main Results:

• CSF levels of IFN-γ, sCD25, IL-10, IL-18, and CXCL9 were significantly higher in the CNS-HLH group compared to the non-CNS HLH group.
• Elevated levels of CSF sCD25, IL-10, IL-18, and CXCL9 were also observed in CNS-HLH patients compared to the demyelination group.
• CSF sCD25, IL-10, and CXCL9 demonstrated high diagnostic efficiency (>0.9 AUC, >80% sensitivity/specificity) for CNS-HLH.
• CSF IL-6 levels did not show significant differences among the groups.

Conclusions:

• CSF IFN-γ, sCD25, IL-10, IL-18, and CXCL9 are significantly elevated in CNS-HLH and can serve as predictive biomarkers.
• CSF CXCL9 may be a more sensitive biomarker for CNS-HLH than IFN-γ.
• CSF IL-6 does not appear to play a significant role in the diagnosis of CNS-HLH.