The elevation of plasma DNA in patients with systemic lupus erythematosus is attributable to increased DNA release and defective DNA binding of mononuclear cells.
BACKGROUND
Although immunoprecipitable DNA has been found in a subgroup of patients with systemic lupus erythematosus (SLE) exhibiting systemic vasculitis and/or central nervous system involvement, the mechanism for elevated plasma DNA in these patients is poorly understood.


METHODS
The plasma DNA concentrations and reactivity of serum and lymphocytes to six species of double-stranded DNA from calf thymus, human placenta, Escherichia coli, Micrococcus lysodeikticus, Clostridium perfringens and poly (dG.dC). poly (dG.dC) were measured in twenty-seven patients with active SLE. To understand the mechanism of increased plasma DNA in SLE, the DNA binding and release of the mononuclear cells were examined.


RESULTS
Compared with the controls, the incidence of the presence of plasma DNA was markedly increased in SLE (59.3% in SLE vs. 7.4% in controls) as detected by counterimmunoelectrophoresis. Except for DNA from Clostridium perfringens, the reactivity of lupus sera to various DNA samples was significantly higher than that of the controls. The reactivity of lymphocytes to 6 species of DNA (as defined by 3H-thymidine incorporation of the cells) was also higher in SLE patients. In DNA binding and releasing experiments, patients with SLE were found to have decreased 3H-DNA binding activity (0.169 +/- 0.018 micrograms/2 x 10(6) cells in SLE vs. 0.283 +/- 0.02 micrograms/2 x 10(6) cells in controls, p = 0.001) but to have increased spontaneous release of DNA (1,465 +/- 412 cpm in SLE vs. 630 +/- 179 cpm in controls, p = 0.0173) in mononuclear cells.


CONCLUSIONS
The results suggest that some subsets of lymphocytes can be sensitized by different DNA samples in vivo to increase endogenous DNA release from mononuclear cells, which in addition to decreased DNA clearance as has been previously reported, may be responsible for the elevation of plasma DNA in patients with SLE.
Tsai
C Y
CY
Department of Medicine, Veterans General Hospital-Taipei, Taiwan, R.O.C.
Yu
C L
CL
Huang
D F
DF
Hsieh
S C
SC
Tsai
Y Y
YY
Tsai
S T
ST
D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood / Q000378:metabolism; D004247:DNA / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000097:blood*; D008297:Male; D009504:Neutrophils / Q000378:metabolism
D000974:Antibodies, Antinuclear; D004247:DNA