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Gene expression changes in multiple sclerosis relapse suggest activation of T and non-T cells

ABSTRACT: paired comparison of RNA expression in peripheral blood mononuclear cells in the same group of 14 multiple sclerosis patients while stable and while in relapse. A defining feature of multiple sclerosis 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. We used microarrays to measure mRNA expression in the peripheral blood of 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. Transcripts with increased expression were primarily expressed in T cells. Pathways analysis suggested involvement of the cytokine network, coagulation and complement cascades, IL-10 signaling, and NF-?B signaling.

ORGANISM(S): Homo sapiens

PROVIDER: GSE19224 | GEO | 2010/06/30

SECONDARY ACCESSION(S): PRJNA120847

REPOSITORIES: GEO

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Project description:Background: The ability to predict the spatial frequency of relapses in multiple sclerosis (MS) would enable treating physicians to decide when to intervene more aggressively and to plan clinical trials more accurately. Methods: In the current study our objective was to determine if subsets of genes can predict the time to the next acute relapse in patients with MS. Data-mining and predictive modeling tools were utilized to analyze a gene-expression dataset of 94 non-treated patients; 62 patients with definite MS and 32 patients with clinically isolated syndrome (CIS). The dataset included the expression levels of 10,594 genes and annotated sequences corresponding to 22,215 gene-transcripts that appear in the microarray. Results: We designed a two stage predictor. The first stage predictor was based on the expression level of 10 genes, and predicted the time to next relapse with a resolution of 500 days (error rate 0.079, p< 0.001). If the predicted relapse was to occur in less than 500 days, a second stage predictor based on an additional different set of 9 genes was used, resulting in a prediction with a resolution of 50 days as to the timing of the next relapse. The error rate of this predictor was 2.3 fold lower than the error rate of random predictions (error rate = 0.35, p<0.001). The predictors were further evaluated and found effective not only in untreated patients but were also valid for MS patients which subsequently received immunomodulatory treatments after the initial testing (the error rate of the first level predictor was < 0.18 with p<0.001 for all the patient groups). Conclusions: We conclude that gene expression analysis is a valuable tool that can be used in clinical practice to predict future MS disease activity. Similar approach can be also useful for dealing with other autoimmune diseases that characterized by relapsing-remitting nature Keywords: Disease prediction Data-mining and predictive modeling tools were utilized to analyze a gene-expression dataset of 94 non-treated patients; 62 patients with definite MS and 32 patients with clinically isolated syndrome (CIS). The dataset included the expression levels of 10,594 genes and annotated sequences corresponding to 22,215 gene-transcripts that appear in the microarray. We designed a two stage predictor. The first stage predictor was based on the expression level of 10 genes, and predicted the time to next relapse with a resolution of 500 days. If the predicted relapse was to occur in less than 500 days, a second stage predictor based on an additional different set of 9 genes was used, resulting in a prediction with a resolution of 50 days as to the timing of the next relapse. The predictors were further evaluated and found effective not only in untreated patients but were also valid for MS patients which subsequently received immunomodulatory treatments after the initial testing.

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Gene expression changes in multiple sclerosis relapse suggest activation of T and non-T cells

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