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Prediction of acute multiple sclerosis relapses by transcription levels of peripheral blood cells.

Gurevich M, Tuller T, Rubinstein U, Or-Bach R, Achiron A - BMC Med Genomics (2009)

Bottom Line: The predictors were further evaluated and found effective both for untreated MS patients and for MS patients that 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).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. Michael.Gurevich@sheba.health.gov.il

ABSTRACT

Background: The ability to predict the spatial frequency of relapses in multiple sclerosis (MS) would enable 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 to give a more accurate estimation of the time till the next relapse (in resolution of 50 days). The error rate of the second stage 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 both for untreated MS patients and for MS patients that 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).

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Regulatory network of the genes that are part of the best FLP and FTP; the network is based on the literature (see the Discussion section).
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Figure 6: Regulatory network of the genes that are part of the best FLP and FTP; the network is based on the literature (see the Discussion section).

Mentions: The IL24 gene is a member of anti-inflammatory IL10 family cytokines involved in immune response. The over-expression of IL24 stimulates pro-apoptotic CADD family genes and activation of apoptosis. On the other hand, IL24 can increase secretion of IFNG in human PBMC. The IFNG by himself is able to repress TGFB mRNA expression as demonstrated in CD18 positive cells [41] and in human lymphocytes it increases mRNA expression of MEFV [42]. Additionally IFNG involved in regulation of the protein NFKBIB (corresponding to the gene PDCD2) that is associated with programmed death of lymphocytes [43-45]. Based on the above relations we reconstructed a unified regulatory network for most of the predictive genes that appear in the FLP (see Figure 6).


Prediction of acute multiple sclerosis relapses by transcription levels of peripheral blood cells.

Gurevich M, Tuller T, Rubinstein U, Or-Bach R, Achiron A - BMC Med Genomics (2009)

Regulatory network of the genes that are part of the best FLP and FTP; the network is based on the literature (see the Discussion section).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2725113&req=5

Figure 6: Regulatory network of the genes that are part of the best FLP and FTP; the network is based on the literature (see the Discussion section).
Mentions: The IL24 gene is a member of anti-inflammatory IL10 family cytokines involved in immune response. The over-expression of IL24 stimulates pro-apoptotic CADD family genes and activation of apoptosis. On the other hand, IL24 can increase secretion of IFNG in human PBMC. The IFNG by himself is able to repress TGFB mRNA expression as demonstrated in CD18 positive cells [41] and in human lymphocytes it increases mRNA expression of MEFV [42]. Additionally IFNG involved in regulation of the protein NFKBIB (corresponding to the gene PDCD2) that is associated with programmed death of lymphocytes [43-45]. Based on the above relations we reconstructed a unified regulatory network for most of the predictive genes that appear in the FLP (see Figure 6).

Bottom Line: The predictors were further evaluated and found effective both for untreated MS patients and for MS patients that 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).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. Michael.Gurevich@sheba.health.gov.il

ABSTRACT

Background: The ability to predict the spatial frequency of relapses in multiple sclerosis (MS) would enable 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 to give a more accurate estimation of the time till the next relapse (in resolution of 50 days). The error rate of the second stage 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 both for untreated MS patients and for MS patients that 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).

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus