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Updated: May 15, 2026
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A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status
Published on: October 20, 2016
A novel multiplexed biomarker panel reveals key molecular pathways in progressive multiple sclerosis
Christina N Heiss1, Lenka Novakova2,3, Markus Axelsson2,3
1Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg 41345, Sweden.
Brain Communications
|May 14, 2026
Summary
Identifying biomarkers for multiple sclerosis progression is crucial. This study found KIT ligand (KITLG) in cerebrospinal fluid predicts progression independent of relapse and MRI activity (PIRMA).
Area of Science:
- Neuroimmunology
- Proteomics
- Biomarker Discovery
Background:
- Progressive multiple sclerosis (MS) involves gradual neurological decline, termed progression independent of relapse and MRI activity (PIRMA).
- Current disease-modifying therapies manage inflammatory activity but cannot predict or prevent PIRMA, highlighting a critical unmet clinical need.
- Identifying individuals at risk for PIRMA is essential for timely and effective therapeutic strategies.
Purpose of the Study:
- To identify novel biomarkers and molecular pathways associated with multiple sclerosis (MS) progression, with a specific focus on PIRMA.
- To explore distinct immunological profiles in different MS subtypes using proteomic analysis.
- To evaluate the prognostic potential of identified biomarkers for predicting disease progression and PIRMA events.
Main Methods:
- Quantified 250 immune-related proteins in cerebrospinal fluid (CSF) and plasma from controls, relapsing-remitting MS (RRMS), and inactive progressive MS (iPMS) patients using the NUcleic acid Linked Immuno-Sandwich Assay (NULISA) panel.
- Utilized longitudinal clinical data to define PIRMA and conversion to secondary progressive MS (SPMS).
- Employed receiver operating characteristic analysis and logistic regression modeling to assess biomarker performance.
Main Results:
- Distinct CSF proteomic signatures were observed in RRMS and iPMS patients compared to controls, with elevated adaptive immunity markers; iPMS showed a shift towards innate immunity markers.
- Low baseline CSF concentrations of KIT ligand (KITLG) in RRMS patients predicted conversion to SPMS and future PIRMA events.
- Plasma levels of interleukin 1 beta and 36 gamma were elevated in RRMS patients who later developed SPMS, with a two-protein model achieving high predictive accuracy (AUC = 0.990).
Conclusions:
- Distinct immunological profiles characterize different multiple sclerosis subtypes, suggesting unique pathogenic mechanisms.
- KIT ligand (KITLG) in CSF emerges as a promising prognostic biomarker for predicting MS progression and PIRMA.
- Interleukin 1 beta and 36 gamma in plasma may serve as predictive biomarkers for SPMS development in RRMS patients, offering potential therapeutic targets.
