Novel biomarkers and interferon signature in secondary progressive multiple sclerosis

J Neuroimmunol. 2024 Apr 15:389:578328. doi: 10.1016/j.jneuroim.2024.578328. Epub 2024 Mar 6.

Abstract

Multiple sclerosis (MS) exhibits poor immune regulation and subnormal interferon (IFN-β) signaling. Secondary Progressive MS displays waning exacerbations, relentless neurodegeneration, and diminished benefit of therapy. We find dysregulated serum protein balance (Th1/Th2) and excessive gene expression in Relapsing-Remitting MS vs. healthy controls (8700 differentially-expressed genes, DEG) and intermediate levels in SPMS (3900 DEG). Olfactory receptor genes (chemosensing), and WNT/ß-catenin (anti-inflammatory, repair) and metallothionein (anti-oxidant) gene pathways, have less expression in SPMS than RRMS. IFN-β treatment decreased pro-inflammatory and increased metallothionein gene expression in SPMS. These gene expression biomarkers suggest new targets for immune regulation and brain repair in this neurodegenerative disease.

Keywords: Immune regulation; Metallothionein; Olfactory receptor; Priming; Progressive multiple sclerosis; WNT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Humans
  • Interferons
  • Metallothionein / genetics
  • Multiple Sclerosis*
  • Multiple Sclerosis, Chronic Progressive*
  • Multiple Sclerosis, Relapsing-Remitting*
  • Neurodegenerative Diseases*

Substances

  • Interferons
  • Biomarkers
  • Metallothionein