In vivo gene expression revealed by cDNA arrays: the pattern in relapsing–remitting multiple sclerosis patients compared with normal subjects

Ramanathan, Murali; Weinstock‐Guttman, Bianca; Nguyen, Linh T.; Badgett, Darlene; Miller, Chris; Patrick, Kara; Brownscheidle, Carol M.; Jacobs, Lawrence

doi:10.1016/s0165-5728(01)00308-3

Cited by 101 publications

(59 citation statements)

References 34 publications

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“…It is reasonable to expect that some of the mRNA changes that distinguish MS patients from controls might also distinguish MS relapses from remissions. Indeed, we found concordant changes in many transcripts which had previously been reported to be changed in MS (16)(17)(18)(19). Of particular interest is the large number of concordant findings with the study of Corvol et al (17).…”

Section: G E N E E X P R E S S I O N C H a N G E S I N M U L T I P L supporting

confidence: 86%

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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Section: G E N E E X P R E S S I O N C H a N G E S I N M U L T I P L supporting

confidence: 86%

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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“…[3][4][5][6] Considering the evidence that in MS autoreactive peripheral blood mononuclear cells (PBMCs), mainly CD4 ϩ lymphocytes, initiate the autoimmune inflammatory process against myelin antigens, we hypothesized that transcriptional profiling of PBMCs could serve to identify a diseasespecific diagnostic signature. This hypothesis is partially supported by the recent results of Ramanathan and colleagues, 7 who analyzed gene arrays of PBMCs in 15 MS patients and 15 healthy subjects; and identified 34 of 4,000 gene transcripts that discriminated those patients in stable remission from controls. Their findings demonstrated that small differences in gene expression (13-35% for overexpressed genes; 11-43% for underexpressed genes) probably were caused by the limited sensitivity of the technology used and the inclusion of only those patients in remission.…”

mentioning

confidence: 66%

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

Achiron

Gurevich

Friedman

et al. 2004

Annals of Neurology

142

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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.

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“…Interestingly, these two haplotypes differ at only one position-at rs987106, in intron 6 of IL7R-suggesting that a functional consequence of this particular polymorphism may underlie the haplotypes' positive and negative associations with the risk of MS. In a recent array-based study of the expression of over 4000 genes in peripheral-blood mononuclear cells from 15 MS patients and 15 age-and sex-matched controls, IL7R was one of only 25 genes that displayed significantly higher expression in patients; 30 overexpression of IL7R, the authors speculate, may result in increased numbers of autoantigen-specific T cells.…”

Section: Discussionmentioning

confidence: 99%

Two genes encoding immune-regulatory molecules (LAG3 and IL7R) confer susceptibility to multiple sclerosis

et al. 2005

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Multiple sclerosis (MS) is a T-cell-mediated disease of the central nervous system, characterized by damage to myelin and axons, resulting in progressive neurological disability. Genes may influence susceptibility to MS, but results of association studies are inconsistent, aside from the identification of HLA class II haplotypes. Whole-genome linkage screens in MS have both confirmed the importance of the HLA region and uncovered non-HLA loci that may harbor susceptibility genes. In this twostage analysis, we determined genotypes, in up to 672 MS patients and 672 controls, for 123 single-nucleotide polymorphisms (SNPs) in 66 genes. Genes were chosen based on their chromosomal positions or biological functions. In stage one, 22 genes contained at least one SNP for which the carriage rate for one allele differed significantly (Po0.08) between patients and controls. After additional genotyping in stage two, two genes-each containing at least three significantly (Po0.05) associated SNPs-conferred susceptibility to MS: LAG3 on chromosome 12p13, and IL7R on 5p13. LAG3 inhibits activated T cells, while IL7R is necessary for the maturation of T and B cells. These results imply that germline allelic variation in genes involved in immune homeostasis-and, by extension, derangement of immune homeostasis-influence the risk of MS.

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In vivo gene expression revealed by cDNA arrays: the pattern in relapsing–remitting multiple sclerosis patients compared with normal subjects

Cited by 101 publications

References 34 publications

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

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

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

Two genes encoding immune-regulatory molecules (LAG3 and IL7R) confer susceptibility to multiple sclerosis

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