Effect of infliximab on gene expression profiling in Behcet's disease.

PURPOSE: Recent studies have demonstrated that a new anti-tumor necrosis factor (TNF)-α antibody, infliximab, is effective in controlling ocular inflammatory attacks in Behçet's disease. In this study, the effect of infliximab on gene expression patterns in peripheral blood mononuclear cells of Behçet's disease patients was investigated before and after initiation of infliximab treatment.

METHODS

A human whole-genome microarray of 54,359 genes was used to analyze mRNA expression profiles of peripheral blood mononuclear cells obtained from four patients (three women, one man, 21-64 years at age) at baseline and at 22 weeks after initiation of infliximab. Quantitative polymerase chain reaction (PCR) analysis was performed for selected up- or downregulated genes, to confirm the microarray results.

RESULTS

Anti-TNF-α therapy reduced the frequency of ocular episodes in three of four patients. Among inflammatory cytokine-related genes, TNF blockade reduced expression of interleukin (IL)-1 receptor type 2, interferon-γ receptors, IL6, IL6 receptor, gp130, and IL17 receptors. Furthermore, gene expression of Toll-like receptor 2 (TLR2), receptor for mycobacterial glycolipid (C-type lectin domain family 4, member E: CLEC4E), and complexin 2 (CPLX2) was downregulated in all patients.

CONCLUSIONS

Several up- or downregulated genes identified in this study may be candidates for further investigation in identifying the molecular mechanism of infliximab in the treatment of Behçet's disease with refractory uveoretinitis.