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From gene expression to serum proteins: biomarker discovery in ankylosing spondylitis
N Haroon1, F W L Tsui, F D O'Shea
1Toronto Western Hospital, Toronto, ON M5T 2S8, Canada.
Objectives:
Studying post-infliximab gene expression changes could provide insights into the pathogenesis of ankylosing spondylitis (AS).
Methods:
Gene expression changes were screened by microarray on peripheral blood RNA of 16 AS patients at baseline and 2 weeks post-infliximab, and selected results were confirmed by quantitative real-time (qRT)-PCR. Corresponding serum-soluble LIGHT (sLIGHT) was estimated by ELISA and the fold change in sLIGHT was correlated to the fold change in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and the Bath AS disease activity index.
Results:
Post-infliximab, 69% of the patients (11/16) achieved an ASAS20 response. Six candidate genes were differentially expressed by microarray; four of which were validated by qRT-PCR. sLIGHT showed the most significant difference. There was good correlation of baseline sLIGHT with CRP (R = 0.60; p = 0.01) and ESR (R = 0.51; p = 0.04). The fold change in sLIGHT correlated with change in both CRP (R = 0.71, p = 0.002) and ESR (R = 0.77, p<0.001).
Conclusion:
LIGHT is significantly downregulated by infliximab. sLIGHT correlated well with changes in inflammatory markers.
