Gene expression changes in peripheral blood mononuclear cells from multiple sclerosis patients undergoing beta-interferon therapy.

OBJECTIVE

Multiple sclerosis (MS) is a disabling idiopathic inflammatory disorder with evidence of immune dysfunction. Current therapies for MS include preparations of beta-interferon (beta IFN). We studied the gene expression patterns in peripheral blood mononuclear cells from relapsing-remitting MS patients undergoing weekly beta IFN-1a therapy (Avonex; 30 mg intramuscular) to identify biomarkers for beta IFN responsiveness.

METHODS

Oligonucleotide microarrays were used for the comparative analysis of gene expression patterns from longitudinal PBMC samples taken from five patients undergoing beta IFN therapy.

RESULTS

On the basis of two-fold changes in expression levels and statistical analyses we selected a candidate diagnostic set of 136 genes that were differentially expressed between pretreatment and IFN-beta-1a-treated MS patients. When we applied this gene set to cluster the specimens according to their expression profiles, the pretreatment samples clustered in one branch, and acute and chronic samples following treatment clustered in another branch. However, the chronic samples from the single clinical non-responder clustered with the pretreatment branch, suggesting that a possible reversal of beta IFN-induced gene expression may be contributing to the poor clinical response.

CONCLUSIONS

These 136 genes represent potential targets for new MS therapeutics and the basis for lack of beta IFN response.