Pronounced interferon-alpha production from plasmacytoid dendritic cells in patients with Behçet's disease following CpG D ODN stimulation

Several lines of evidence point to a polarized T-helper-1 (Th1) immune response in Behçet's disease (BD). Interferon (IFN)-alpha which has an ability to promote strong Th1 type immune response has been shown to increase in patients with BD. In order to clarify if plasmacytoid dendritic cells (pDCs) abnormally respond to a stimulus in patients with BD, we investigated the levels of intracellular IFN-alpha and beta in pDCs with or without CpG D ODN stimulation. The study population consisted of 8 patients with clinically active BD, 8 ankylosing spondilitis (AS) patients having active disease and 11 healthy volunteers. pDC subsets in peripheral blood mononuclear cells (PBMCs) cultures were analysed by flow cytometry. The percentage of IFN-alpha+ pDCs in unstimulated PBMCs cultures from patients BD was significantly higher (p=0.036) than in AS and HC. But this difference disappeared in stimulated PBMCs cultures (p=0.167). The mean fluorescence intensity (MFI) of IFN-alpha+ pDCs in stimulated PBMCs cultures of BD patients was significantly higher than those from patients with AS and HC. The percentage of IFN-beta+ pDCs in unstimulated PBMCs cultures from patients with BD and AS was significantly higher (p=0.004) than in HC. But this difference was not significant in stimulated PBMCs cultures (p=0.694). When compared to healthy subjects, the MFI of IFN-beta + pDCs in unstimulated and stimulated PBMCs cultures from patients with BD and AS was not different (p=0.287, p=0.152, respectively). In patients with BD, the percentage and MFI of IFN-alpha+ pDCs were higher (p=0.012 for all) in stimulated PBMCs cultures as compared to unstimulated ones. We suggest that increased frequency of IFN-alpha+ pDC in BD patients and the higher sensitiveness of these cells to CpG D ODN stimulus contribute to high serum IFN-alpha levels found in these patients which eventually resulted in Th1 type immune response.