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OP0096 Transcriptome analysis in rheumatoid arthritis treated with a tnf neutralising tnf receptor: fusion protein (etanercept)
  1. J Kekow1,
  2. S Drynda1,
  3. D Koczan2,
  4. HJ Thiesen2
  1. 1Clinic of Rheumatology, Otto-Von-Guericke-University, Magdeburg
  2. 2Institut for Immunology, University of Rostock, Rostock, Germany

Abstract

Background Treatment with etanercept (Enbrel) results in a rapid and sustained improvement of disease activity in patients with refractory rheumatoid arthritis (RA). Although changes in the expression of single proteins, particularly cytokines and proteases, could be demonstrated in the past at the protein and mRNA level, new methods are neccessary to provide insight into the complex mechanisms which occur after neutralisation of TNFα.

Objectives Oligonucleotide arrays can provide a broad picture of the state of cells by monitoring the expression levels of thousands of genes at the same time. Here we report the application of DNA array technology (Affymetrix) to cover changes in the expression levels under etanercept treatment.

Methods Mononuclear cells (PBMC) and neutrophils (PMN) from peripheral blood were prepared applying standard procedures, synovial fluid (SF) was obtained from both knees. Total RNA for analysis was isolated from PBMC, PMN and SF-cells at different time points in the course of treatment.

Results The expression level of 5600 transcripts was analysed. The most expressed genes were found in SF-cells. About 3.3%, 2.4% and 0.2% of the assessed genes in PBMC, PMN and SF-cells, respectively, showed significant changes in gene expression in either direction (i.e. increase with a fold change >/= 3, decrease with a fold change.

Conclusion The group of genes which are up- or downregulated included a number of genes which are known to be involved in transcription, chemotaxis, cell adhesion as well as genes not previously examined in the context of rheumatoid arthritis.

The results have to be considered preliminary and confirmed in further experiments.

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