CpG motif-containing DNA fragments from sera of patients with systemic lupus erythematosus proliferate mononuclear cells in vitro

Objective. To characterize DNA in sera of patients with systemic lupus eryt hematasus (SLE) in terms of size. guanine plus cytosine (G+C) content (by p ercentage), CpG dinucleotide (CpG) (percentage), and effects on mononuclear cells (MNC), Methods, Nine DNA clones were sequenced. Oligodeoxynucleotides with the cha racteristic CpG motif (TTCGAA or PuPuCGPyPy) were examined for their prolif erative effect on MNC by [H-3]thymidine incorporation, expression of HLA-DR and intercellular adhesion molecule (ICAM)-1 on monocytes by now cytometry , and mRNA levels encoding interleukin 12 (IL-12) and interferon-gamma (IFN -gamma) by semiquantitative reverse transcription polymerase chain reaction . Results. The size of DNA clones ranged from 87 to 318 bp (mean +/- SD, 177 +/- 68) and enrichment in G+C and CpG ranged from 34.7 to 69.7% (48.1 +/- 1 0.7) and 0.63 to 12.8% (4.0 +/- 4.1), respectively. Three of 9 clones conta ined the characteristic CpG motif. Oligonucleotides: proliferated MNC, and augmented HLA-DR and ICAM-1 expression in company with an increase of mRNA encoding IL-12 and IFN-gamma. Conclusion. Circulating CpG motif-containing DNA fragments in SLE increased mRNA encoding IL-12 and IFN-gamma, which in turn increased HLA-DR and ICAM -1 on monocytes, resulting in MNC proliferation. This mechanism could contr ibute to the pathogenesis of SLE.