BAFF/APRIL system in pediatric OMS: relation to severity, neuroinflammation, and immunotherapy

Area of Science:

• Neuroimmunology
• Pediatric Neurology
• Biomarker Discovery

Background:

• Pediatric opsoclonus-myoclonus syndrome (OMS) is a neuroinflammatory disorder linked to neuroblastoma, with implicated B-cell dysregulation.
• The precise role of B-cell modulating cytokines, such as B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), in OMS pathogenesis remains unclear.

Purpose of the Study:

• To investigate the role of BAFF and APRIL as potential biomarkers of disease activity in pediatric OMS.
• To evaluate BAFF and APRIL as potential treatment biomarkers in OMS patients.

Main Methods:

• Quantification of soluble BAFF and APRIL in cerebrospinal fluid (CSF) and serum using ELISA in 433 children (296 OMS, 109 controls, 28 OIND).
• Flow cytometry analysis of BAFF-R expression on circulating B cells.
• Correlation of cytokine levels with motor severity, oligoclonal bands, chemokines, and response to immunotherapies (ACTH, corticosteroids, IVIg, rituximab).

Main Results:

• Elevated CSF BAFF concentrations in untreated OMS and OIND correlated with disease severity and inflammatory markers.
• CSF BAFF levels decreased significantly following treatment with ACTH/corticosteroids.
• Serum APRIL levels increased with intravenous immunoglobulin (IVIg) therapy, while serum BAFF increased with rituximab treatment.

Conclusions:

• Heterogeneity in CSF BAFF expression suggests its potential utility as part of a biomarker panel for OMS activity.
• Selective changes in serum APRIL (with IVIg) and BAFF (with rituximab), alongside CSF BAFF reduction (with ACTH/steroids), indicate potential as treatment biomarkers.