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Response of peripheral blood mononuclear cells from lupus patients to stimulation by CpG oligodeoxynucleotides
R A Zeuner1, D M Klinman, G Illei
1Center for Biologics Evaluation and Research/Food and Drug Administration, Bethesda, Maryland, USA.
Objectives:
Increased levels of hypomethylated CpG-containing DNA in sera from patients with systemic lupus erythematosus (SLE) may contribute to the initiation and/or perpetuation of the disease. This study characterizes the in vitro response of peripheral blood mononuclear cells (PBMC) from SLE patients to CpG DNA.
Methods:
Secretion of cytokines and IgM, cell proliferation and up-regulation of co-stimulatory molecules were evaluated in PBMC from SLE patients (n=24) and normal controls (n=24) after stimulation with synthetic oligodeoxynucleotides (ODN) containing CpG motifs.
Results:
Up-regulation of co-stimulatory molecules and the secretion of interferon-alpha and interleukin-6 (IL-6) in response to CpG ODN was significantly reduced in monocytes and dendritic cells from SLE patients. Secretion of interferon-gamma by natural killer (NK) cells was also reduced. In contrast, the IgM and IL-10 response of B cells to CpG ODN was normal.
Conclusion:
Monocytes, dendritic cells and NK cells from SLE patients respond abnormally to CpG ODN stimulation, which may contribute to the cytokine imbalance observed in SLE.
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