Blood transcriptional signatures of multiple sclerosis: unique gene expression of disease activity.
Multiple sclerosis (MS) is a central nervous system disease with an unpredictable course and outcome. Peripheral blood mononuclear cells (PBMCs) are involved in the disease pathogenesis and induce active demyelination. Using oligonucleotide microarrays, we identified a statistically significant transcriptional signature of 1,109 genes in PBMCs from 26 MS patients, irrespective of disease activation state or immunomodulatory treatment. This signature contains genes that implicate underlying processes involved in MS pathogenesis including T-cell activation and expansion, inflammation, and apoptosis. Another transcriptional signature of 721 genes involved in cellular recruitment, epitope spreading, and escape from regulatory immune surveillance identified MS patients in acute relapse compared with remission. Our results offer new opportunity for understanding the mechanisms involved in MS and indicate that gene expression patterns in PBMCs contain information about a remote-target disease process that may be useful for diagnosis and future tailoring of therapeutic strategies for MS.
Achiron
Anat
A
Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer 52621, Israel. achiron@post.tau.ac.il
Gurevich
Michael
M
Friedman
Nir
N
Kaminski
Naftali
N
Mandel
Mathilda
M
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000328:Adult; D017209:Apoptosis / Q000235:genetics; D001499:Bayes Theorem; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D013601:T-Lymphocytes / Q000378:metabolism; D015533:Transcriptional Activation
D000276:Adjuvants, Immunologic