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Inducer in Systemic Lupus Erythematosus1
*
Section of Immunology, Department of Veterinary Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden; and
Section of Rheumatology, Department of Medical Sciences, University Hospital, Uppsala, Sweden
Patients with systemic lupus erythematosus (SLE) have increased
blood levels of IFN-
, which correlate to disease activity. We
previously identified an IFN--inducing factor (IIF) in the blood of
SLE patients that activated the natural IFN--producing cells in
cultures of normal PBMC. The SLE-IIF contained DNA and IgG, possibly as
small immune complexes. In our study, we demonstrated that SLE-IIF
correlated to the presence of anti-dsDNA Abs in patients and
contained anti-dsDNA Abs as an essential component. Purified
anti-DNA Abs or SLE-IgG caused only a weak IFN- production in
cultures of normal PBMC in the presence of costimulatory IFN-2b.
However, they converted the plasmid pcDNA3, which itself induced no
IFN- production in PBMC, into an efficient IFN- inducer. A human
monoclonal anti-ss/dsDNA Ab had the same effect. This
IFN--inducing activity of the plasmid was abolished by methylation,
suggesting that unmethylated CpG DNA motifs were important. Like IIF in
SLE serum, the combination of SLE-IgG and pcDNA3 appeared to stimulate
IFN- production in natural IFN--producing cells, a unique cell
population resembling immature dendritic cells. The IFN- production
was greatly enhanced by IFN-2b and IFN-ß, and for SLE-IIF it was
also enhanced by GM-CSF but inhibited by IL-10. We have therefore
identified a new function of DNA-anti-DNA Ab complexes, IFN-
induction, that might be important in the pathogenesis of
SLE.
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