Response of peripheral blood mononuclear cells from lupus patients to stimulation by CpG oligodeoxynucleotides.
OBJECTIVE
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.


CONCLUSIONS
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.
Zeuner
R A
RA
Center for Biologics Evaluation and Research/Food and Drug Administration, Bethesda, Maryland, USA.
Klinman
D M
DM
Illei
G
G
Yarboro
C
C
Ishii
K J
KJ
Gursel
M
M
Verthelyi
D
D
D000368:Aged; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D015854:Up-Regulation
C408982:CPG-oligonucleotide; D016207:Cytokines; D007075:Immunoglobulin M; D009838:Oligodeoxyribonucleotides