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From gene expression to serum proteins: biomarker discovery in Ankylosing Spondylitis
  1. Nigil Haroon (nigil.haroon{at}uhn.on.ca)
  1. Toronto Western Research Institute, Canada
    1. Florence W L Tsui (ftsui{at}uhnresearch.ca)
    1. Toronto Western Research Institute, Canada
      1. Finbar D O'Shea (boshea{at}uhnresearch.ca)
      1. Toronto Western Research Institute, Canada
        1. Basil Chiu (bchiu{at}uhnres.utoronto.ca)
        1. Toronto Western Research Institute, Canada
          1. Hing Wo Tsui (htsui{at}uhnresearch.ca)
          1. Toronto Western Research Institute, Canada
            1. Hongwei Zhang (hzhang{at}chondrogene.com)
            1. GeneNews Limited, Canada
              1. Wayne K Marshall (wmarshall{at}chondrogene.com)
              1. GeneNews Limited, Canada
                1. Robert D Inman (robert.inman{at}uhn.on.ca)
                1. Toronto Western Research Institute, Canada

                  Abstract

                  Objectives: Studying the gene expression changes following infliximab infusion for ankylosing spondylitis patients could provide novel insights into this disease.

                  Methods: Sixteen AS patients who received infliximab were enrolled in the study. Microarray analysis was done on peripheral blood RNA at baseline and 2 weeks post-infliximab to screen for changes in gene expression and selected results were confirmed by qRT-PCR. Soluble LIGHT (sLIGHT) in corresponding serum samples was estimated by ELISA and compared to clinical data. The fold change in sLIGHT was correlated by Spearman’s correlation to the fold change in ESR, CRP and BASDAI.

                  Results: At 2 weeks following infliximab, 69% of the patients (11/16) achieved an ASAS20 response. Compared to baseline, six candidate genes were differentially expressed by microarray analysis; four of which were validated by qRT-PCR. LIGHT expression showed the most significant difference. There was a good correlation between the baseline values of sLIGHT versus 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: The gene expression of LIGHT was significantly downregulated by infliximab and the changes in sLIGHT correlated well with changes in other markers of inflammation.

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