Long-term genome-wide blood RNA expression profiles yield novel molecular response candidates for IFN-beta-1b treatment in relapsing remitting MS

Pharmacogenomics
Robert H GoertschesUwe Klaus Zettl

Abstract

In multiple sclerosis patients, treatment with recombinant IFN-beta (rIFN-beta) is partially efficient in reducing clinical exacerbations. However, its molecular mechanism of action is still under scrutiny. We used DNA microarrays (Affymetrix, CA, USA) and peripheral mononuclear blood cells from 25 relapsing remitting multiple sclerosis patients to analyze the longitudinal transcriptional profile within 2 years of rIFN-beta administration. Sets of differentially expressed genes were attained by applying a combination of independent criteria, thereby providing efficient data curation and gene filtering that accounted for technical and biological noise. Gene ontology term-association analysis and scientific literature text mining were used to explore evidence of gene interaction. Post-therapy initiation, we identified 42 (day 2), 175 (month 1), 103 (month 12) and 108 (month 24) differentially expressed genes. Increased expression of established IFN-beta marker genes, as well as differential expression of circulating IFN-beta-responsive candidate genes, were observed. MS4A1 (CD20), a known target of B-cell depletion therapy, was significantly downregulated after one month. CMPK2, FCER1A, and FFAR2 appeared as hitherto unrecognized...Continue Reading

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Methods Mentioned

BETA
electrophoresis
Chip
reverse transcription PCR
PCR

Software Mentioned

MAID
R
GeneAnnot
PaxGene
GCOS
GeneChip
Pathway Architect
GOstats
PathwayArchitect
Bioconductor

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