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Updated: Jun 27, 2026
Scoring Central Nervous System Inflammation, Demyelination, and Axon Injury in Experimental Autoimmune Encephalomyelitis
Published on: February 23, 2024
Serum inflammatory proteomic signatures define chronic inflammatory demyelinating polyneuropathy and inform on
Amol Keshavasa Bhandage1, Frauke Stascheit2, Hannah Preßler2
1Department of Medical Sciences, Clinical Neurophysiology, Uppsala University, Uppsala, Sweden.
Background:
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is an immune-mediated neuropathy with heterogeneous presentation and variable treatment response. Blood-based biomarkers remain lacking, and interpretation is confounded by widespread immunoglobulin (IG) therapy. The primary aim was to identify serum inflammatory proteomic signatures associated with CIDP; exploratory aims included associations with disease activity, phenotype, and treatment response.
Methods:
In this case-control study, 92 proteins were quantified using multiplex proximity extension assay and ELISA in 358 sera samples from patients with CIDP, multiple sclerosis (MS), and IG-treated myasthenia gravis (MG) as well as age- and sex- matched healthy controls (HC). Logistic regression with Bonferroni correction, principal component analysis, and correlation analyses were applied to identify differential expression across diagnoses and CIDP subgroups.
Findings:
Seven proteins, TNFSF14, CD40, SIRT2, CCL3, IL8, TGFα, and uPA, consistently distinguished CIDP from HC, MS, and IG-treated MG, representing disease-specific signatures independent of IG exposure. Six additional proteins (STAMBP, CASP-8, EN-RAGE, OSM, HGF, and CXCL6) were IG-responsive. CXCL9, CDCP1, and CCL20 correlated with muscle weakness, while calprotectin and neurofilament light chain reflected broader inflammatory and axonal injury signatures. Patients with unstable active disease exhibited higher CCL4, IL-8, CCL3, FGF-21, and IL-17A. IL-8, EN-RAGE, and CASP-8 predicted clinical improvement, and IL-5 tracked longitudinal disability changes.
Interpretation:
CIDP is characterised by distinct serum inflammatory proteomic signatures comprising disease-specific and IG-responsive signatures. These candidate biomarkers may support improved patient stratification, disease monitoring, and prediction of treatment response, advancing individualised therapy in CIDP.
Funding:
Erling-Persson Foundation, Sweden (#2022_0030 to ARP) and the German Research Foundation, Germany (KFO5023 TP8 to AM).