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Intrathecal B-cell accumulation and axonal damage distinguish MRI-based benign from aggressive onset in MS

Sinah Engel1, Michaela Friedrich1, Muthuraman Muthuraman1

  • 1From the Department of Neurology (S.E., M.F., M.M., F.S., S.G., S.B., F.Z., F.L.), Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn), University Medical Center of the Johannes Gutenberg University, Mainz; and Institute of Medical Biostatistics (A.P.), Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.

Neurology(R) Neuroimmunology & Neuroinflammation
|August 28, 2019
PubMed
Abstract

Insights

Combining cerebrospinal fluid (CSF) B-cell markers and neurofilament light chain (NfL) in serum or CSF improves the distinction between benign and aggressive multiple sclerosis (MS). This composite score offers personalized treatment strategies for early MS patients.

Area of Science:

  • Neuroimmunology
  • Biomarker Discovery
  • Multiple Sclerosis Pathogenesis

Background:

  • Distinguishing between benign and aggressive forms of multiple sclerosis (MS) in its early stages is crucial for effective treatment.
  • Current diagnostic methods, including MRI, require complementary biomarkers to accurately assess disease activity and progression.

Purpose of the Study:

  • To evaluate the added value of multiple biomarkers in cerebrospinal fluid (CSF) and serum for differentiating MRI-defined benign from aggressive MS.
  • To identify a combination of biomarkers that enhances diagnostic accuracy in early MS.

Main Methods:

  • Analysis of 93 patients with clinically isolated syndrome (CIS) or early MS, categorized into severity groups based on MRI.
  • Flow cytometry for leukocyte subsets, ELISA for CSF neurofilament light chain (NfL) and chitinase-3-like protein 1 (CHI3L1), and single molecule array for serum NfL.
  • Receiver operating characteristic and support vector machine analyses to assess diagnostic performance of individual and combined biomarkers.

Main Results:

  • CSF CD20+/CD14+ ratios and NfL levels in both CSF and serum were significantly different between high and low MRI severity groups.
  • CSF CHI3L1 levels did not show significant differences.
  • Combined CSF CD20+/CD14+ ratios and NfL levels (serum or CSF) significantly improved diagnostic accuracy, outperforming single biomarkers.

Conclusions:

  • A composite score integrating markers of intrathecal B-cell accumulation and axonal damage (NfL) effectively distinguishes MS severity in early disease stages.
  • This combined approach facilitates personalized treatment decisions and immunotherapy strategies for MS patients.

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