Novel biomarkers and interferon signature in secondary progressive multiple sclerosis.

ABSTRACT

Multiple sclerosis (MS) exhibits poor immune regulation and subnormal interferon (IFN-ß) 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-ß 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.