ArticleBlood advances2026
Novel CSF biomarkers for facilitating diagnosis of CNS-HLH from other neuroinflammatory disorders.
Article in Blood advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Beyond the Storm: CXCL9 and the New Era of Precision Hemophagocytic Lymphohistiocytosis Diagnostics.Diagnostics (Basel, Switzerland) · 2026Review
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11 authors.
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Abstract
abstractCentral nervous system (CNS)-hemophagocytic lymphohistiocytosis (HLH) can mimic other neuroinflammatory disorders (ONID), often leading to misdiagnosis. Current diagnostic studies do not reliably distinguish CNS-HLH from ONID. We hypothesized that novel cerebrospinal fluid (CSF) biomarkers identified using unbiased proteomic analysis can facilitate diagnosis of CNS-HLH from ONID. Banked CSF samples were categorized into 3 groups, CNS-HLH, ONID, and controls without CNS inflammation. Proteomic analysis was performed on 25 samples per group (total N = 75). Proteins demonstrating significant changes (>1.5-fold higher and P< .05) in the CNS-HLH compared with ONID and associated with HLH pathophysiology were selected as candidate biomarkers. Cross-platform validation of candidate biomarkers, along with known biomarkers CXCL9 and osteopontin, was performed using enzyme-linked immunosorbent assay (ELISA). One hundred twenty-two proteins were identified on CSF proteomic analysis at 99% confidence. Of these, 10 proteins demonstrated a >1.5-fold change with a P<.05 in CNS-HLH compared with ONID. SerpinG1, lysozyme, and CD14 were selected as candidate biomarkers. ELISA confirmed significant elevation of all 5 biomarkers in CNS-HLH relative to ONID. Median SerpinG1 levels were1242.9 ng/mL in CNS-HLH vs 292.2 ng/mL in ONID (P ≤ .001), lysozyme 222.2 ng/mL vs 65.6 ng/mL (P = .001), and CD14 180.3 ng/mL vs 64.5 ng/mL (P ≤ .001). Median CXCL9 levels were 223.7 ng/mL in CNS-HLH vs 15.5 ng/mL in ONID (P ≤ .001), and osteopontin levels were 356.5 ng/mL vs 92.9 ng/mL (P = .001). These findings demonstrate that novel CSF biomarkers SerpinG1, lysozyme, CD14, and CXCL9 can facilitate diagnosis of CNS-HLH from ONID.
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