Oligoclonal M bands unveil occult inflammation in multiple sclerosis

Bonaventura Casanova1, Jessica Castillo1, Carlos Quintanilla-Bordás1

  • 1Neuroimmunology Unit. València University and Polytechnic Hospital La Fe. València, Spain.

Abstract

Insights

Patients with multiple sclerosis (pwMS) and oligoclonal M bands (OCMB) show elevated serum neurofilament light chain (s-NFL) levels, even without active inflammation, suggesting OCMB indicate a distinct disease pathway.

Area of Science:

  • Neurology
  • Neuroimmunology
  • Biomarker Research

Background:

  • Multiple Sclerosis (MS) patients with oligoclonal M bands (OCMB) in cerebrospinal fluid (CSF) face a higher risk of progressing to a secondary progressive course.
  • This suggests a unique pathophysiological pathway in these individuals.

Purpose of the Study:

  • To investigate the relationship between serum neurofilament light chain (s-NFL) levels and the presence of OCMB in people with MS (pwMS).
  • To analyze this relationship in the absence of inflammatory activity and assess the impact of aging.
  • To compare s-NFL levels in pwMS with OCMB against those without OCMB and healthy controls (HC).

Main Methods:

  • A study involving 130 pwMS and 124 HC, with pwMS selected for the absence of clinical or radiological signs of acute inflammation.
  • Inflammation absence was confirmed by no relapses or gadolinium-enhancing lesions on MRI within three months of s-NFL measurement.
  • s-NFL was quantified using SIMOa technology, and OCMB were analyzed in CSF via isoelectric focusing and immunoblotting.

Main Results:

  • PwMS with OCMB exhibited significantly higher s-NFL levels (11.4 pg/mL) compared to pwMS without OCMB (8.9 pg/mL) and HC (9.0 pg/mL), despite the absence of overt inflammation.
  • A positive, exponential correlation was observed between age and s-NFL levels.
  • The most substantial age-related increases in s-NFL were noted in pwMS with OCMB in their CSF.

Conclusions:

  • OCMB in pwMS are associated with elevated s-NFL levels, even without detectable inflammatory activity.
  • These findings suggest OCMB may indicate an underlying inflammatory process not evident on standard MRI.
  • The heightened s-NFL and accelerated age-related increase in pwMS with OCMB may explain their poorer prognosis.

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