Increased concentrations of antibody-bound circulatory cell-free DNA in rheumatoid arthritis.
BACKGROUND
Increased concentrations of cell-free DNA have been found in several disorders and have been interpreted as evidence of increased rates of cell death or turnover. Evidence from in vitro and animal experiments suggests that DNA may play a role in the pathogenesis of rheumatoid arthritis (RA).


METHODS
We measured cell-free DNA in plasma and serum from patients with RA and healthy controls by use of quantitative PCR for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) DNA. We used protein G Sepharosetrade mark bead adsorption of plasma and elution to isolate antibody-bound DNA.


RESULTS
In paired plasma and serum samples of 16 healthy controls the median GAPDH copies were 4500 genome equivalents (GE)/mL plasma (range 319-21 000) and in 26 RA patients 17 000 GE/mL plasma (2100-2 375 000, P = 0.0001). In the serum from normal controls the median GAPDH copies were 35 000 GE/mL (1700-239 000) and from RA patients 222 000 GE/mL (21 000-2 375 000, P = 0.004). A median of 81% of the cell-free DNA in RA was associated with antibody compared with 9% in healthy controls (P = 0.001). The concentrations of DNA did not vary with the type of therapy patients received.


CONCLUSIONS
These results provide new evidence for a role of cell-free DNA-antibody complexes in the etiology of RA, suggest new avenues for basic research, and may prove to be relevant to diagnosis and assessment of therapy.
Zhong
Xiao-Yan
XY
Laboratory for Prenatal Medicine, University Women's Hospital, Department of Research, University Hospital Basel, Basel, Switzerland.
von Mühlenen
Ines
I
Li
Ying
Y
Kang
Anjeung
A
Gupta
Anurag Kumar
AK
Tyndall
Alan
A
Holzgreve
Wolfgang
W
Hahn
Sinuhe
S
Hasler
Paul
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D015331:Cohort Studies; D004247:DNA / Q000097:blood*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D010865:Pilot Projects; D011485:Protein Binding
D000974:Antibodies, Antinuclear; D004247:DNA; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases