Gene expression profile in multiple sclerosis patients and healthy controls: identifying pathways relevant to disease

Bomprezzi, Roberto; Ringnér, Markus; S, Kim; Bittner, Michael; Khan, Javed; Chen, Yidong; Elkahloun, Abdel G.; Yu, Aimee Y.; Bielekova, Bibiana; Meltzer, Paul S.; Martin, Roland; McFarland, Henry F.; Trent, Jeffrey M.

doi:10.1093/hmg/ddg221

Cited by 187 publications

(128 citation statements)

References 29 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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“…Nevertheless, controversial differences between MS patients and healthy controls have been found in gene expression studies. Whereas earlier genetic studies showed HSPA1A overexpression in MS lesions (64,65,68), more recently HSPA1A expression was shown to be downregulated in the PBMC of MS patients (141)(142)(143). Histological studies in MS and EAE tissues have confirmed HSPA1A upregulation in CNS lesions; however, surprisingly, analysis of the baseline expression of Hsp70 genes in PBMC revealed no differences among MS patients, healthy controls or patients with rheumatoid arthritis.…”

Section: Hsp Genetic Studiesmentioning

confidence: 90%

Heat Shock Protein 70: Roles in Multiple Sclerosis

Mansilla

Montalbán

Espejo

2012

Mol Med

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Heat shock proteins (HSP) have long been considered intracellular chaperones that possess housekeeping and cytoprotective functions. Consequently, HSP overexpression was proposed as a potential therapy for neurodegenerative diseases characterized by the accumulation or aggregation of abnormal proteins. Recently, the discovery that cells release HSP with the capacity to trigger proinflammatory as well as immunoregulatory responses has focused attention on investigating the role of HSP in chronic inflammatory autoimmune diseases such as multiple sclerosis (MS). To date, the most relevant HSP is the inducible Hsp70, which exhibits both cytoprotectant and immunoregulatory functions. Several studies have presented contradictory evidence concerning the involvement of Hsp70 in MS or experimental autoimmune encephalomyelitis (EAE), the MS animal model. In this review, we dissect the functions of Hsp70 and discuss the controversial data concerning the role of Hsp70 in MS and EAE.

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“…20 Several groups have also examined gene expression profiles of PBMCs in a variety of autoimmune disorders, including SLE, 21,22 RA 20,23 and multiple sclerosis. 24 With the exception for SLE, 6 these studies have not revealed clear-cut expression 'signatures' of autoimmune disease. Bovin et al 13 have recently examined peripheral blood gene expression profiles from a data set of 14 RA patients and seven healthy controls with the aim of identifying differences between rheumatoid factor (RF)-negative and RF-positive patients.…”

mentioning

confidence: 99%