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Intrathecal B cell activation and memory impairment in multiple sclerosis

Lorenzo Gaetani1, Nicola Salvadori2, Giovanni Brachelente3

  • 1Section of Neurology, Department of Medicine and Surgery, University of Perugia, Piazzale Severi 8, Perugia 06132, Italy..

Multiple Sclerosis and Related Disorders
|March 21, 2024
PubMed

Insights

Intrathecal B cells, indicated by a higher kappa-index, are linked to verbal memory decline in people with multiple sclerosis (pwMS). This immune cell activity may cause memory issues, even without significant MRI-detected brain damage.

Area of Science:

  • Neuroimmunology
  • Cognitive Neuroscience

Background:

  • Cognitive impairment (CI) is a significant disability in people with multiple sclerosis (pwMS).
  • The precise mechanisms driving CI in pwMS are not fully understood, with a potential role for immune cells in the central nervous system.
  • This study investigated the link between intrathecal B cells and cognitive function in pwMS.

Purpose of the Study:

  • To explore the hypothesis that intrathecal B cells influence cognitive performance in pwMS.
  • To assess the relationship between B cell activation markers in cerebrospinal fluid (CSF) and cognitive test results.
  • To determine if intrathecal B cell activity is associated with cognitive impairment independently of MRI-visible brain damage.

Main Methods:

  • Retrospective analysis of 39 newly diagnosed pwMS with available CSF.
  • Measurement of the kappa (κ)-index as a biomarker for intrathecal B cell activation.
  • Cognitive assessment using the Brief Repeatable Battery of Neuropsychological Tests (BRBN).
  • Quantification of MRI-derived metrics including T2 lesion load and brain volumes.

Main Results:

  • A significantly higher κ-index was observed in pwMS with verbal memory impairment.
  • The κ-index showed a negative association with BRBN tests measuring verbal memory and information processing speed.
  • Multivariate analyses confirmed that a higher κ-index was independently associated with poorer verbal memory performance and increased likelihood of verbal memory impairment.

Conclusions:

  • Intrathecal B cell activation may be a key driver of verbal memory impairment in pwMS.
  • This association appears to be independent of the extent of MRI-detectable brain damage.
  • Targeting intrathecal B cells could be a potential therapeutic strategy for cognitive dysfunction in multiple sclerosis.
Abstract

Keywords:
BiomarkersCerebrospinal fluidCognitive impairmentFree light chainsKappa indexMultiple sclerosis

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