Influence of anti-TNF therapy on monocyte gene expression in rheumatoid arthritis

Background and objective

The joint in rheumatoid arthritis (RA) is characterized by pannus formation and cartilage/bone destruction. In RA, not only tissue macrophages but also blood monocytes (MO) are known to be activated and spontaneously release inflammatory mediators. However, genes and functional pathways involved in RA monocyte activation are recognized and characterized only in part.

Of all techniques for differential mRNA expression analysis, DNA arrays raise most expectations and are applied for drug discovery and compound testing in preclinical or clinical studies. This technique may also enable the identification of genes and expression patterns associated with the type of disease, stage of activation, disease progression and molecular therapeutic mechanisms. For functional interpretation, the experimental concept is important. Considering drawbacks and benefits, analysis of defined cell populations is advantageous for functional interpretation.

Methods

Therefore, we analyzed the expression profile of untouched negatively separated MO using the Affymetrix U133A/B array system. MO were obtained from normal donors, patients with active RA before and after several months of anti-TNF antibody therapy. Bioinformatic analysis of gene expression included background correction, normalization, comparative statistics and cluster analysis.

Results

So far, six characteristic clusters have been obtained, including genes relevant to RA and induced or decreased upon therapy. Furthermore, RA regulated genes were identified, which returned to 'normal' upon anti-TNF treatment, indicating selective molecular effects of the drug.

Conclusion

These promising results could open new avenues for the identification of novel genes for a general definition of MO/macrophage activation patterns and for pathways activated or blocked during different stages of the disease or therapy-induced remission in RA.