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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
09:41

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis

Published on: July 19, 2019

Age-related blood transcriptional regulators affect disease progression in pediatric multiple sclerosis

Eitan Shavit1, Shay Menascu2, Anat Achiron2

  • 1Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel; St. George's Hospital Medical School, University of London, London, United Kingdom; Arrow project for medical research education, Sheba Medical Center, Ramat-Gan, Israel.

Neurobiology of Disease
|December 9, 2022
PubMed

Insights

Pediatric onset multiple sclerosis (POMS) exhibits more severe disease activity than adult onset multiple sclerosis (AOMS). Gene expression analysis reveals distinct molecular mechanisms, including cell cycle and B lymphocyte pathways, contributing to POMS severity.

Area of Science:

  • Neuroimmunology
  • Genomics
  • Pediatric Neurology

Background:

  • Pediatric onset multiple sclerosis (POMS) is defined as multiple sclerosis with onset before age 18.
  • POMS patients often present with more severe disease activity compared to adult onset multiple sclerosis (AOMS) patients.
  • The molecular mechanisms underlying these clinical differences remain largely unknown.

Purpose of the Study:

  • To investigate the molecular differences in gene expression between POMS and AOMS.
  • To identify potential molecular mechanisms contributing to the distinct clinical presentations of POMS.
  • To explore the relationship between gene expression patterns and disease severity in POMS.

Main Methods:

  • Gene expression analysis of Peripheral Blood Mononuclear Cells (PBMCs) from 22 POMS and 16 AOMS patients using Affymetrix microarrays.
  • Identification of Differentially Expressed Genes (DEGs) between POMS and AOMS using Partek software.
  • Clinical assessment via Expanded Disability Status Scale (EDSS) and brain MRI lesion load, with functional analysis by Ingenuity Pathway Analysis.

Main Results:

  • POMS patients showed higher EDSS scores and greater T1 and T2 brain MRI lesion volumes compared to AOMS patients.
  • A total of 551 DEGs were identified in POMS, enriched in cell cycling, B lymphocyte signaling, and senescence pathways.
  • 183 DEGs correlated with T2 lesion volume, and 29 common DEGs between POMS age-related regulators and healthy subjects suggested a role in disease severity.

Conclusions:

  • Higher transcriptional levels of genes in cell cycle, cell migration, and B cell proliferation pathways are associated with POMS.
  • Age-associated genes and transcription factors appear to promote these pathways in POMS.
  • These molecular findings provide a better understanding of the aggressive clinical course observed in pediatric onset multiple sclerosis.
Abstract

Keywords:
Gene expressionPediatric multiple sclerosisPeripheral blood mononuclear cells

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