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Novel approaches to detect serum biomarkers for clinical response to interferon-beta treatment in multiple sclerosis.

Gandhi KS, McKay FC, Diefenbach E, Crossett B, Schibeci SD, Heard RN, Stewart GJ, Booth DR, Arthur JW - PLoS ONE (2010)

Bottom Line: However, some patients fail to respond to treatment.APOA1, A2M, and FIBB were identified as putative clinical response markers.In a complementary targeted approach, Cytometric Beadarray (CBA) analysis showed no significant difference in the serum concentration of IL-6, IL-8, MIG, Eotaxin, IP-10, MCP-1, and MIP-1alpha, between clinical responders and non-responders, despite the association of these proteins with IFNbeta treatment in MS.

View Article: PubMed Central - PubMed

Affiliation: Westmead Millennium Institute, University of Sydney, Sydney, Australia.

ABSTRACT
Interferon beta (IFNbeta) is the most common immunomodulatory treatment for relapsing-remitting multiple sclerosis (RRMS). However, some patients fail to respond to treatment. In this study, we identified putative clinical response markers in the serum and plasma of people with multiple sclerosis (MS) treated with IFNbeta. In a discovery-driven approach, we use 2D-difference gel electrophoresis (DIGE) to identify putative clinical response markers and apply power calculations to identify the sample size required to further validate those markers. In the process we have optimized a DIGE protocol for plasma to obtain cost effective and high resolution gels for effective spot comparison. APOA1, A2M, and FIBB were identified as putative clinical response markers. Power calculations showed that the current DIGE experiment requires a minimum of 10 samples from each group to be confident of 1.5 fold difference at the p<0.05 significance level. In a complementary targeted approach, Cytometric Beadarray (CBA) analysis showed no significant difference in the serum concentration of IL-6, IL-8, MIG, Eotaxin, IP-10, MCP-1, and MIP-1alpha, between clinical responders and non-responders, despite the association of these proteins with IFNbeta treatment in MS.

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Related in: MedlinePlus

IL-6 and eotaxin concentration comparison between CR and CNR in serum.
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pone-0010484-g004: IL-6 and eotaxin concentration comparison between CR and CNR in serum.

Mentions: IL-6 (p = 0.2), IL-8 (p = 0.53), MIG (p = 0.3), MCP-1 (p = 0.61), eotaxin (p = 0.11), IP-10 (p = 0.81), and MIP-1α (p = 0.61) serum concentrations were not significantly different between CR and CNR to IFNβ. However, both eotaxin and IL-6 levels were high in CR as compared to CNR, but not significantly different, partly because some of the samples were below the level of detection (Figure 4). Eotaxin is produced by Th2 cells [53] and has previously been found to be reduced in serum of MS patients as compared to HC [32]. Hence a trend towards elevation of serum eotaxin in CRs could be an effect of Th2 bias generated by IFNβ treatment. CR also showed a trend towards a higher percentage of samples with detectable serum IL-6, another Th2 cytokine. Interestingly, increased IL-6 in IFNβ treated patients has been found to be associated with lower relapse rates and disability [54].


Novel approaches to detect serum biomarkers for clinical response to interferon-beta treatment in multiple sclerosis.

Gandhi KS, McKay FC, Diefenbach E, Crossett B, Schibeci SD, Heard RN, Stewart GJ, Booth DR, Arthur JW - PLoS ONE (2010)

IL-6 and eotaxin concentration comparison between CR and CNR in serum.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2864746&req=5

pone-0010484-g004: IL-6 and eotaxin concentration comparison between CR and CNR in serum.
Mentions: IL-6 (p = 0.2), IL-8 (p = 0.53), MIG (p = 0.3), MCP-1 (p = 0.61), eotaxin (p = 0.11), IP-10 (p = 0.81), and MIP-1α (p = 0.61) serum concentrations were not significantly different between CR and CNR to IFNβ. However, both eotaxin and IL-6 levels were high in CR as compared to CNR, but not significantly different, partly because some of the samples were below the level of detection (Figure 4). Eotaxin is produced by Th2 cells [53] and has previously been found to be reduced in serum of MS patients as compared to HC [32]. Hence a trend towards elevation of serum eotaxin in CRs could be an effect of Th2 bias generated by IFNβ treatment. CR also showed a trend towards a higher percentage of samples with detectable serum IL-6, another Th2 cytokine. Interestingly, increased IL-6 in IFNβ treated patients has been found to be associated with lower relapse rates and disability [54].

Bottom Line: However, some patients fail to respond to treatment.APOA1, A2M, and FIBB were identified as putative clinical response markers.In a complementary targeted approach, Cytometric Beadarray (CBA) analysis showed no significant difference in the serum concentration of IL-6, IL-8, MIG, Eotaxin, IP-10, MCP-1, and MIP-1alpha, between clinical responders and non-responders, despite the association of these proteins with IFNbeta treatment in MS.

View Article: PubMed Central - PubMed

Affiliation: Westmead Millennium Institute, University of Sydney, Sydney, Australia.

ABSTRACT
Interferon beta (IFNbeta) is the most common immunomodulatory treatment for relapsing-remitting multiple sclerosis (RRMS). However, some patients fail to respond to treatment. In this study, we identified putative clinical response markers in the serum and plasma of people with multiple sclerosis (MS) treated with IFNbeta. In a discovery-driven approach, we use 2D-difference gel electrophoresis (DIGE) to identify putative clinical response markers and apply power calculations to identify the sample size required to further validate those markers. In the process we have optimized a DIGE protocol for plasma to obtain cost effective and high resolution gels for effective spot comparison. APOA1, A2M, and FIBB were identified as putative clinical response markers. Power calculations showed that the current DIGE experiment requires a minimum of 10 samples from each group to be confident of 1.5 fold difference at the p<0.05 significance level. In a complementary targeted approach, Cytometric Beadarray (CBA) analysis showed no significant difference in the serum concentration of IL-6, IL-8, MIG, Eotaxin, IP-10, MCP-1, and MIP-1alpha, between clinical responders and non-responders, despite the association of these proteins with IFNbeta treatment in MS.

Show MeSH
Related in: MedlinePlus