Blood serum DNA in patients with rheumatoid arthritis is considerably enriched with fragments of ribosomal repeats containing immunostimulatory CpG-motifs.
We previously hypothesized that the sequence of transcribed region of human ribosomal repeats is selectively accumulated in circulating extracellular DNA due to its increased resistance to double-strand breaks caused by accumulation of single-chain breaks produced by nucleases. The contents of rDNA in blood serum DNA and in DNA from leukocytic nuclei both in healthy donors and in patients with rheumatoid arthritis were compared using dot hybridization method. By the content of non-methylated CpG-repeats, transcribed region of rDNA is identical to bacterial DNA, which is characterized by potent immunostimulatory effect. The transcribed region of rDNA (13.3 kb) contains more than 200 CpG-motifs capable of interacting with TLR9 receptors, which are the mediators of the cell immune response to the action of CpG-rich DNA fragments. The data suggest that DNA from dead cells circulating in the peripheral blood is enriched with sequences possessing potent immunostimulatory properties.
Veiko
N N
NN
Medical and Genetic Research Center, Research Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow, Russia. ribgene@rambler.ru
Shubaeva
N O
NO
Ivanova
S M
SM
Speranskii
A I
AI
Lyapunova
N A
NA
Spitkovskii
D M
DM
D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D016022:Case-Control Studies; D018899:CpG Islands / Q000276:immunology*; D004247:DNA / Q000097:blood*; D004275:DNA, Ribosomal / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000276:immunology*; D006801:Humans; D051217:Toll-Like Receptor 9 / Q000276:immunology
D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; D051217:Toll-Like Receptor 9; D004247:DNA