From gene expression to serum proteins: biomarker discovery in ankylosing spondylitis

Ann Rheum Dis. 2010 Jan;69(1):297-300. doi: 10.1136/ard.2008.102277.

Abstract

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.

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Biomarkers / blood
  • Blood Proteins / metabolism*
  • Blood Sedimentation
  • C-Reactive Protein / metabolism
  • Female
  • Gene Expression Profiling / methods
  • Humans
  • Infliximab
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis / methods
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Severity of Illness Index
  • Spondylitis, Ankylosing / blood
  • Spondylitis, Ankylosing / drug therapy*
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / blood
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Biomarkers
  • Blood Proteins
  • TNFSF14 protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 14
  • C-Reactive Protein
  • Infliximab