OBJECTIVE: To perform systematic transcriptomic analysis of multiple sclerosis 
(MS) risk genes in peripheral blood mononuclear cells (PBMCs) of subjects with 
distinct MS stages and describe the pathways characterized by dysregulated gene 
expressions.
METHODS: We monitored gene expression levels in PBMCs from 3 independent cohorts 
for a total of 297 cases (including clinically isolated syndromes (CIS), 
relapsing-remitting MS, primary and secondary progressive MS) and 96 healthy 
controls by distinct microarray platforms and quantitative PCR. Differential 
expression and pathway analyses for distinct MS stages were defined and 
validated by literature mining.
RESULTS: Genes located in the vicinity of MS risk variants displayed altered 
expression in peripheral blood at distinct stages of MS compared with the 
healthy population. The frequency of dysregulation was significantly higher than 
expected in CIS and progressive forms of MS. Pathway analysis for each MS 
stage-specific gene list showed that dysregulated genes contributed to 
pathogenic processes with scientific evidence in MS.
CONCLUSIONS: Systematic gene expression analysis in PBMCs highlighted selective 
dysregulation of MS susceptibility genes playing a role in novel and well-known 
pathogenic pathways.