Potential biomarkers for multiple sclerosis stage from targeted proteomics and microRNA sequencing

Area of Science:

• Neuroimmunology
• Biomarker Discovery
• Central Nervous System Disorders

Background:

• Multiple sclerosis (MS) is a chronic central nervous system demyelinating disease.
• Current diagnostic and prognostic tools for MS subtypes are limited.
• Need for circulating biomarkers to guide treatment decisions in MS.

Purpose of the Study:

• To identify novel protein and microRNA biomarkers in cerebrospinal fluid and serum for multiple sclerosis (MS).
• To differentiate between MS subtypes, specifically relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS).
• To investigate biomarkers associated with the conversion from RRMS to SPMS.

Main Methods:

• Targeted proteomics (92 proteins) and microRNA sequencing on serum and cerebrospinal fluid samples.
• Analysis of a cross-sectional case-control cohort (Cohort I) and a prospective MS cohort (Cohort II).
• Meta-analysis combining data from both cohorts to identify differentially expressed markers.

Main Results:

• 13 proteins differed between MS and controls in cerebrospinal fluid; no microRNAs.
• Serum analysis revealed 10 proteins and 16 microRNAs differentiating RRMS from SPMS.
• Longitudinal analysis showed a peak in granzyme B proteins and enrichment of immune cell-related microRNAs during RRMS to SPMS conversion.

Conclusions:

• Serum proteins and microRNAs show potential as biomarkers for distinguishing MS subtypes.
• Conversion to SPMS is associated with increased granzyme B and specific immune microRNAs.
• Immune cell-driven processes may play a role in MS progression.