Quantitative and qualitative changes in gene expression patterns characterize the activity of plaques in multiple sclerosis

Lotti Tajouri, Albert S. Mellick, Kevin J. Ashton, Anthony E G Tannenberg, Rashed M. Nagra, Wallace W. Tourtellotte, Lyn R. Griffiths

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Abstract

Multiple sclerosis (MS) is a complex autoimmune disorder of the CNS with both genetic and environmental contributing factors. Clinical symptoms are broadly characterized by initial onset, and progressive debilitating neurological impairment. In this study, RNA from MS chronic active and MS acute lesions was extracted, and compared with patient matched normal white matter by fluorescent cDNA microarray hybridization analysis. This resulted in the identification of 139 genes that were differentially regulated in MS plaque tissue compared to normal tissue. Of these, 69 genes showed a common pattern of expression in the chronic active and acute plaque tissues investigated (P value<0.0001, ρ=0.73, by Spearman's ρ analysis); while 70 transcripts were uniquely differentially expressed (≥1.5-fold) in either acute or chronic active tissues. These results included known markers of MS such as the myelin basic protein (MBP) and glutathione S-transferase (GST) M1, nerve growth factors, such as nerve injury-induced protein 1 (NINJ1), X-ray and excision DNA repair factors (XRCC9 and ERCC5) and X-linked genes such as the ribosomal protein, RPS4X. Primers were then designed for seven array-selected genes, including transferrin (TF), superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPX1), GSTP1, crystallin, alpha-B (CRYAB), phosphomannomutase 1 (PMM1) and tubulin β-5 (TBB5), and real time quantitative (Q)-PCR analysis was performed. The results of comparative Q-PCR analysis correlated significantly with those obtained by array analysis (r=0.75, P value<0.01, by Pearson's bivariate correlation). Both chronic active and acute plaques shared the majority of factors identified suggesting that quantitative, rather than gross qualitative differences in gene expression pattern may define the progression from acute to chronic active plaques in MS.

Original languageEnglish
Pages (from-to)170-183
Number of pages14
JournalMolecular Brain Research
Volume119
Issue number2
DOIs
Publication statusPublished - 26 Nov 2003
Externally publishedYes

Fingerprint

Multiple Sclerosis
Gene Expression
DNA Repair
alpha-Crystallin B Chain
Genes
X-Linked Genes
Myelin Basic Protein
Ribosomal Proteins
Protein S
Nerve Growth Factors
Tubulin
Microarray Analysis
Transferrin
Oligonucleotide Array Sequence Analysis
Real-Time Polymerase Chain Reaction
X-Rays
RNA
Polymerase Chain Reaction
Wounds and Injuries
Proteins

Cite this

Tajouri, Lotti ; Mellick, Albert S. ; Ashton, Kevin J. ; Tannenberg, Anthony E G ; Nagra, Rashed M. ; Tourtellotte, Wallace W. ; Griffiths, Lyn R. / Quantitative and qualitative changes in gene expression patterns characterize the activity of plaques in multiple sclerosis. In: Molecular Brain Research. 2003 ; Vol. 119, No. 2. pp. 170-183.
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abstract = "Multiple sclerosis (MS) is a complex autoimmune disorder of the CNS with both genetic and environmental contributing factors. Clinical symptoms are broadly characterized by initial onset, and progressive debilitating neurological impairment. In this study, RNA from MS chronic active and MS acute lesions was extracted, and compared with patient matched normal white matter by fluorescent cDNA microarray hybridization analysis. This resulted in the identification of 139 genes that were differentially regulated in MS plaque tissue compared to normal tissue. Of these, 69 genes showed a common pattern of expression in the chronic active and acute plaque tissues investigated (P value<0.0001, ρ=0.73, by Spearman's ρ analysis); while 70 transcripts were uniquely differentially expressed (≥1.5-fold) in either acute or chronic active tissues. These results included known markers of MS such as the myelin basic protein (MBP) and glutathione S-transferase (GST) M1, nerve growth factors, such as nerve injury-induced protein 1 (NINJ1), X-ray and excision DNA repair factors (XRCC9 and ERCC5) and X-linked genes such as the ribosomal protein, RPS4X. Primers were then designed for seven array-selected genes, including transferrin (TF), superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPX1), GSTP1, crystallin, alpha-B (CRYAB), phosphomannomutase 1 (PMM1) and tubulin β-5 (TBB5), and real time quantitative (Q)-PCR analysis was performed. The results of comparative Q-PCR analysis correlated significantly with those obtained by array analysis (r=0.75, P value<0.01, by Pearson's bivariate correlation). Both chronic active and acute plaques shared the majority of factors identified suggesting that quantitative, rather than gross qualitative differences in gene expression pattern may define the progression from acute to chronic active plaques in MS.",
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Quantitative and qualitative changes in gene expression patterns characterize the activity of plaques in multiple sclerosis. / Tajouri, Lotti; Mellick, Albert S.; Ashton, Kevin J.; Tannenberg, Anthony E G; Nagra, Rashed M.; Tourtellotte, Wallace W.; Griffiths, Lyn R.

In: Molecular Brain Research, Vol. 119, No. 2, 26.11.2003, p. 170-183.

Research output: Contribution to journalArticleResearchpeer-review

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