Novel Approaches to Detect Serum Biomarkers for Clinical Response to Interferon-β Treatment in Multiple Sclerosis

Kaushal S Gandhi,Stephen D Schibeci,Eve Diefenbach,Jonathan W Arthur,Ben Crossett,Fiona C Mckay,Graeme J Stewart,Robert N Heard,David R Booth,Gian Maria Fimia

doi:10.1371/journal.pone.0010484

Kaushal S Gandhi, Stephen D Schibeci + Show 8 more

Open Access

https://doi.org/10.1371/journal.pone.0010484

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Journal: PloS one	Publication Date: May 5, 2010
Citations: 40	License type: CC BY 4.0

Affiliation: University of Sydney, Westmead Institute

Abstract

Interferon beta (IFNβ) 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 IFNβ. 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-1α, between clinical responders and non-responders, despite the association of these proteins with IFNβ treatment in MS.

Highlights

Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating autoimmune disorder of the central nervous system (CNS)
The targeted approach suggests that eotaxin and IL-6 require further investigation as possible Interferon beta (IFNb) clinical response markers
Both discovery-driven and targeted approaches demonstrated a requirement for a larger sample size to fully characterize clinical response markers using a proteomic approach

Summary

Introduction

Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating autoimmune disorder of the central nervous system (CNS). IFNb treatment significantly reduces the frequency of relapses, lesion load, and disability in RRMS and SPMS patients [1,2]. Up to a third of patients do not respond to this therapy [3,4]. It is important to identify people who do not respond clinically to IFNb promptly, so they can be treated with less immunogenic IFNb or alternate therapies at an early stage in the disease course [7,8]. It has been shown that RRMS patients who are clinical responders to IFNb treatment show a more inflammatory and less neurodegenerative disease at the commencement of the treatment compared to those who do not [9], no specific biomarkers were found to differentiate these groups

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