Novel Csf Biomarkers for Facilitating Diagnosis of CNS-HLH From Other Neuroinflammatory Disorders

Authors

• Sharat Chandra
• Kenneth D Greis
• Somchai Chutipongtanate
• Nathan Luebbering
• Aaron Webster
• Kelsey E Poisson
• Kristen S Fisher
• Kristi Smiley
• Rebecca A Marsh
• Michael B Jordan
• Stella M Davies

Language

English

Publication Date

2-24-2026

Journal

Blood Advances

DOI

10.1182/bloodadvances.2025016297

PMID

41212999

PMCID

PMC12914418

PubMedCentral® Posted Date

11-12-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Central 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.

Keywords

Humans, Biomarkers, Proteomics, Neuroinflammatory Diseases, Male, Female, Middle Aged, Adult, Diagnosis, Differential

Published Open-Access

yes

Recommended Citation

Chandra, Sharat; Greis, Kenneth D; Chutipongtanate, Somchai; et al., "Novel Csf Biomarkers for Facilitating Diagnosis of CNS-HLH From Other Neuroinflammatory Disorders" (2026). Faculty, Staff and Students Publications. 7697.
https://digitalcommons.library.tmc.edu/baylor_docs/7697