Blood transcriptional signatures of multiple sclerosis: Unique gene expression of disease activity

Achiron, Anat; Gurevich, Michael; Friedman, Nir; Kaminski, Naftali; Mandel, Mathilda

doi:10.1002/ana.20008

Cited by 142 publications

(105 citation statements)

References 49 publications

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“…19,[20][21][22] Additionally, recent microarray studies in human CNS disorders (multiple sclerosis, stroke and seizure) as well as rodent models of such disease suggest specific gene expression signatures in PBMCs. 23,24 Microarrays allow high-throughput gene expression profiling of transcriptional reactivity. Applied to PBMCs, they may detect signatures of biological processes that underlie adaptive and pathological reactions to traumatic stress as they unfold over time.…”

mentioning

confidence: 99%

Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors

et al. 2005

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Trauma survivors show marked differences in the severity and persistence of post-traumatic stress disorder (PTSD) symptoms. Early symptoms subside in most, but persist as acute and chronic PTSD in a significant minority. The underlying molecular mechanisms or outcome predictors determining these differences are not known. Molecular markers for identifying any mental disorder are currently lacking. Gene expression profiling during the triggering and development of PTSD may be informative of its onset and course. We used oligonucleotide microarrays to measure peripheral blood mononuclear cell (PBMC) gene expression of trauma survivors at the emergency room and 4 months later. Gene expression signatures at both time points distinguished survivors who met DSM-IV diagnostic criteria for PTSD at 1 and 4 months, from those who met no PTSD criterion. Expression signatures at both time points correlated with the severity of each of the three PTSD symptom clusters assessed 4 months following exposure among all survivors. Results demonstrate a general reduction in PBMCs' expression of transcription activators among psychologically affected trauma survivors. Several differentiating genes were previously described as having a role in stress response. These findings provide initial evidence that peripheral gene expression signatures following trauma identify an evolving neuropsychiatric disorder and are informative of its key clinical features and outcome. Replications in larger samples, as well as studies focusing on specific markers within the signatures discovered, are warranted to confirm and extend the diagnostic utility and pathogenetic implications of our results. Molecular Psychiatry (2005) 10, 500-513.

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confidence: 99%

Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors

et al. 2005

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“…These previous studies demonstrated changes in PB gene expression patterns with among these, genes involved in the p53 and apoptosis pathway. [17][18][19][20][21] Whereas these studies provided insight into the genes that were differentially expressed between MS patients and healthy controls, the issue of transcript-based disease heterogeneity was not addressed.…”

Section: Discussionmentioning

confidence: 99%

A subtype of multiple sclerosis defined by an activated immune defense program

et al. 2006

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Given the heterogeneous nature of multiple sclerosis (MS), we applied DNA microarray technology to determine whether variability is reflected in peripheral blood (PB) cells. In this study, we studied whole-blood gene expression profiles of 29 patients with relapsing-remitting MS (RRMS) and 25 age-and sex-matched healthy controls. We used microarrays with a complexity of 43K cDNAs. The data were analyzed using sophisticated pathway-level analysis in order to provide insight into the deregulated peripheral immune response programs in MS. We found a remarkable elevated expression of a spectrum of genes known to be involved in immune defense in the PB of MS patients compared to healthy individuals. Cluster analysis revealed that the increased expression of these genes was characteristic for approximately half of the patients. In addition, the gene signature in this group of patients was comparable with a virus response program. We conclude that the transcriptional signature of the PB cells reflects the heterogeneity of MS and defines a sub-population of RRMS patients, who exhibit an activated immune defense program that resembles a virus response program, which is supportive for a link between viruses and MS.

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“…Thus, changes in gene expression in peripheral blood leukocytes might clarify the mechanism of MS relapses. Previous studies using microarray technology to measure gene expression changes in MS relapse had interesting results, but are limited by multiple factors, including the available microarrays, the use of unpaired samples, small sample sizes, and possible alteration of gene expression during sample preparation (5)(6)(7)(8). We have extended these findings using a larger population of subjects with paired relapse and stable samples from each, and comprehensive measurements of mRNA expression.…”

Section: Introductionmentioning

confidence: 84%

“…Dendrogram constructed using BRB ArrayTools with centered correlation and average linkage. The branch labels give the experiment number (1)(2)(3)(4)(5), the subject number (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), clinical status, treatment, and gender. The samples from the first two experiments formed large clusters.…”

Section: R E S E a R C H A R T I C L E M O L M Ementioning

confidence: 99%

Gene Expression Changes in Multiple Sclerosis Relapse Suggest Activation of T and Non-T Cells

Lindsey

Agarwal

Tan

2010

Mol Med

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A defining feature of multiple sclerosis (MS) is the occurrence of clinical relapses separated by periods of clinical stability. Better understanding of the events underlying clinical relapse might suggest new approaches to treatment. The objective of this study was to measure changes in the expression of RNA in the blood during relapse. We used microarrays to measure mRNA expression in paired samples from 14 MS patients during clinical relapse and while stable. Seventy-one transcripts changed expression at the P < 0.001 significance level. The most notable finding was decreased expression of transcripts with regulatory function, expressed primarily in non-T cells. These decreased transcripts included the interleukin-1 receptor antagonist, which had a corresponding decrease in the protein concentration in serum. Transcripts with increased expression were expressed primarily in T cells. Pathways analysis suggested involvement of the cytokine network, coagulation and complement cascades, IL-10 signaling and NF-κB signaling. We conclude that there are alterations of mRNA expression in both T cells and non-T cells during MS relapse.

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Blood transcriptional signatures of multiple sclerosis: Unique gene expression of disease activity

Cited by 142 publications

References 49 publications

Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors

Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors

A subtype of multiple sclerosis defined by an activated immune defense program

Gene Expression Changes in Multiple Sclerosis Relapse Suggest Activation of T and Non-T Cells

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