title: Novel approaches to detect serum biomarkers for clinical response to interferon-beta treatment in multiple sclerosis.
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.
authors.affiliation: Westmead Millennium Institute, University of Sydney, Sydney, Australia.
authors.forename: Kaushal S
authors.initials: KS
authors.lastname: Gandhi
authors.forename: Fiona C
authors.initials: FC
authors.lastname: McKay
authors.forename: Eve
authors.initials: E
authors.lastname: Diefenbach
authors.forename: Ben
authors.initials: B
authors.lastname: Crossett
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Schibeci
authors.forename: Robert N
authors.initials: RN
authors.lastname: Heard
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Stewart
authors.forename: David R
authors.initials: DR
authors.lastname: Booth
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Arthur
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D054413:Chemokine CCL11 / Q000097:blood; D003710:Demography; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy*; D018401:Sample Size; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D015850:Interleukin-6; D016899:Interferon-beta
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