Gene expression profiling in multiple sclerosis: a disease of the central nervous system, but with relapses triggered in the periphery?
The aetiology of multiple sclerosis (MS), an autoimmune demyelinating disease of the central nervous system (CNS), includes both genetic and environmental factors, but the pathogenesis is still incompletely known. We performed gene expression profiling on paired cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) samples from 26 MS patients without immunomodulatory treatment, sampled in relapse or remission, and 18 controls using Human Genome U133 plus 2.0 arrays (Affymetrix). In the CSF, 939 probe sets detected differential expression in MS patients compared to controls, but none in PBMCs, confirming that CSF cells might mirror the disease processes. The regulation of selected transcripts in CSF of MS patients was confirmed by quantitative PCR. Unexpectedly however, when comparing MS patients in relapse to those in remission, 266 probe sets detected differential expression in PBMCs, but not in CSF cells, indicating the importance of events outside of the CNS in the triggering of relapse.
Brynedal
Boel
B
The Multiple Sclerosis Research Group, Centre for Molecular Medicine, Department of Clinical Neuroscience, Karolinska Institutet, CMM L8:00, 171 76 Stockholm, Sweden. boel.brynedal@ki.se
Khademi
Mohsen
M
Wallström
Erik
E
Hillert
Jan
J
Olsson
Tomas
T
Duvefelt
Kristina
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D053263:Gene Regulatory Networks / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis / Q000134:cerebrospinal fluid; D012008:Recurrence; D012680:Sensitivity and Specificity; D014157:Transcription Factors / Q000032:analysis / Q000134:cerebrospinal fluid; D055815:Young Adult
D015415:Biomarkers; D005819:Genetic Markers; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D014157:Transcription Factors