Characterizing CSF inflammatory proteomics in pediatric post-hemorrhagic hydrocephalus and Anti-NMDAR encephalitis
Taylor Broudy1, Ankush Bansal1, Akilah Pascall2,3
1Center for Neuroscience Research, Children's National Hospital, Washington, DC, 20010, USA.
Journal of Neuroinflammation
|December 9, 2025
Summary
Pediatric neuroinflammation in post-hemorrhagic hydrocephalus (PHH) and N-methyl-D-aspartate receptor encephalitis (NMDARE) shows distinct proteomic signatures. PHH involves complement and coagulation pathways, while NMDARE shows lymphocyte-driven inflammation, suggesting potential biomarkers.
Area of Science:
- Neuroscience
- Immunology
- Proteomics
Background:
- Neuroinflammation is a critical factor in central nervous system (CNS) diseases.
- Pediatric CNS diseases have fewer proteomic studies compared to adult conditions.
- High-sensitivity proteomic profiling is needed to detect low-abundance inflammatory mediators in pediatric CNS diseases.
Purpose of the Study:
- To characterize neuroinflammatory signatures in pediatric diseases using high-sensitivity proteomic profiling.
- To compare proteomic profiles of post-hemorrhagic hydrocephalus (PHH), N-methyl-D-aspartate receptor encephalitis (NMDARE), and brain tumor-associated hydrocephalus.
- To identify potential biomarkers for pediatric CNS inflammatory conditions.
Main Methods:
- Cerebrospinal fluid (CSF) samples from pediatric patients and controls were analyzed using the Olink Explore platform.
- 641 inflammation-related proteins were profiled, and differentially abundant proteins (DAPs) were identified using limma.
- Pathway enrichment and protein-protein interaction network analyses were performed to understand functional modules.
Main Results:
- PHH samples showed significant differences from controls, with enriched complement activation, coagulation, and platelet degranulation pathways.
- NMDARE samples displayed distinct, narrower signatures involving IL-10/IL-18 signaling and humoral immunity markers (IGLC2, MZB1, CD79B).
- NELL2 was consistently downregulated in PHH, and immunoglobulin markers were upregulated in NMDARE, suggesting potential biomarker utility.
Conclusions:
- PHH and NMDARE exhibit unique neuroinflammatory proteomic signatures.
- PHH is characterized by broad inflammation involving complement and coagulation pathways, potentially indicating chronic neuroinflammation.
- NMDARE presents a lymphocyte-driven, antibody-mediated autoimmune profile, with NELL2 and immunoglobulin markers as potential biomarkers.
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