Blood serum DNA in patients with rheumatoid arthritis is considerably enriched with fragments of ribosomal repeats containing immunostimulatory CpG-motifs

Вейко, Н. Н.; Shubaeva, N. O.; Ivanova, Saška; Speranskiĭ, A I; Lyapunova, N. A.; Spitkovskii, D. M.

doi:10.1007/s10517-006-0354-2

Cited by 36 publications

(30 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We showed that TRrDNA fragments have an in vitro stimulatory effect on lymphocytes. It may be suggested that selective accumulation of these fragments in extracellular DNA [1] may modulate function of the immune system. This work was supported by the Russian Foundation for Basic Research (grants No.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Stimulatory effect of fragments from transcribed region of ribosomal repeat on human peripheral blood lymphocytes

et al. 2006

Self Cite

View full text Add to dashboard Cite

Fragments from the transcribed region of the ribosomal repeat include considerable amounts of unmethylated CpG DNA motifs. These motifs activate immune cells via the interaction with Toll receptors. In vitro experiments confirmed the stimulatory effect of transcribed region of ribosomal repeat on human lymphocytes. Culturing of lymphocytes in a medium containing 2-20,000 ng/ml fragments from transcribed region of ribosomal repeat was accompanied by structural changes in the nucleus in a considerable number of cells. These changes manifested in translocation of pericentromeric heterochromatin from the membrane to the center of the nucleus and activation of the nucleolus and were accompanied by a significant increase in interleukin-6 production and slight stimulation of tumor necrosis factor-a synthesis. The transcribed region of the ribosomal repeat and E. coli DNA had various effects on quantitative parameters of lymphocytes. Our results suggest the existence of mechanisms of stimulation not mediated by the interaction of CpG DNA motifs with Toll receptors.

show abstract

Section: Resultsmentioning

confidence: 99%

“…We described a previously unknown property of fragments from transcribed region of ribosomal repeat (TRrDNA): they are accumulated in extracellular peripheral blood DNA in healthy individuals and, especialy, in patients with rheumatoid arthritis (RA) [1]. The increase in the content of TRrDNA fragments in extracellular DNA is important for the immune system.…”

mentioning

confidence: 99%

Stimulatory effect of fragments from transcribed region of ribosomal repeat on human peripheral blood lymphocytes

et al. 2006

Self Cite

View full text Add to dashboard Cite

show abstract

“…Interestingly, it has been demonstrated that ribosomal DNA (rDNA) containing hypomethylated DNA released from host derived dead cells is present at increased levels in the RA serum (Veiko et al, 2006). This rDNA fragments are thought to stimulate TLR9 signalling.…”

Section: Toll-like Receptors (Tlr) In Ramentioning

confidence: 99%

Innate immunity, epigenetics and autoimmunity in rheumatoid arthritis

Rodrigues

Jüngel

2009

Molecular Immunology

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by the progressive and irreversible destruction of joints.RA remains an incurable condition, although a new class of drugs, biologicals, have made a major breakthrough in targeting and/or eliminating the immune cells, including T cells, B cells and monocytes/macrophages from the joints. That we cannot (yet?) cure the disease is most likely due to the lack of therapeutic targeting the endogenously activated RA synovial fibroblasts (RASF).Most interestingly, RASF express Toll-like receptors 1-6 rendering them prone to activation by exogenous and endogenous TLR ligands and resulting in the production of numerous powerful chemokines and cytokines. These factors are responsible for the repopulation of immune cells in the joints after ceasing cell depleting therapies.To characterize the molecular mechanisms of synovial activation, a new approach studying the epigenetic characteristics of RASF has been recently undertaken.Thereby, the pattern of histone acetylation, DNA methylation and gene expression regulating microRNA are being explored.Since auto-antibodies have the most predictive and diagnostic value for RA, it is challenging to study more comprehensively the contribution of auto-antibodies to the disease. A new screening technique, serological analysis of recombinant human cDNA expression library (SEREX), adapted from cancer research allowed for the identification of novel auto-antibodies in RA, including anti-serpin E2 auto-antibodies.The serpin E2 auto-antibodies were found to inhibit the activity of serpin E2 and have potentially a functional role in the disease. The recent findings in the field of innate immunity, epigenetics and autoimmunity related to the pathogenesis of RA are in the scope of this review. 2

show abstract

“…Intraarticularly injected bacterial DNA containing CpG motifs induces transient arthritis and aggravates collagen-induced arthritis in mice [17,18]. The data suggest that DNA from dead cells circulating in the peripheral blood is capable of interacting with TLR9 receptors and enriched with sequences possessing potent immunostimulatory properties [19,29,30]. Recently, the increased expression of TLR9 in the peripheral blood B cells of RA patients versus healthy donors was reported, suggesting that TLR9 plays a role in the hyperreactivity of RA B lymphocytes [31].…”

Section: Introductionmentioning

confidence: 97%

The investigation of toll-like receptor 3, 9 and 10 gene polymorphisms in Turkish rheumatoid arthritis patients

et al. 2010

View full text Add to dashboard Cite

Toll-like receptors (TLRs) play an important role in the induction and regulation of the innate immune system or adaptive immune responses. Genetic variations within human TLRs have been reported to be associated with a range of immune-related diseases. This study was conducted to investigate the frequencies of TLR3 rs3775290, TLR9 rs187084, and TLR10 rs4129009 polymorphisms and to detect between polymorphisms and autoantibody positive as RF, collagen type II, anti-RNP, and anti-CCP in patient group. We performed a case-control study of 100 rheumatoid arthritis (RA) cases and 100 healthy controls matched on age, sex, and residence. All polymorphisms in TLRs were determined by polymerase chain reaction-based restriction fragment length polymorphism. Serum autoantibody level was measured using quantitative ELISA. SNPs were genotyped in all samples. Our results showed that TT genotype for SNP 1237 T/C increased the RA risk significantly (p < 0.05). No statistically significant differences were found in the TLR3 and TLR10 genotypes or allele distribution between RA patients and control individuals. No associations were noted with autoantibody production and TLR3, TLR9, and TLR10 polymorphisms genotypes (p > 0.05). Our study suggests that a single nucleotide polymorphism (rs187084) in TLR9 gene may be a susceptibility factor for RA in Turkish population. Further studies are required to explore the role of TLRs gene polymorphisms in the risk of RA, especially in ethnically different populations to confirm our results.

show abstract

Blood serum DNA in patients with rheumatoid arthritis is considerably enriched with fragments of ribosomal repeats containing immunostimulatory CpG-motifs

Cited by 36 publications

References 15 publications

Stimulatory effect of fragments from transcribed region of ribosomal repeat on human peripheral blood lymphocytes

Stimulatory effect of fragments from transcribed region of ribosomal repeat on human peripheral blood lymphocytes

Innate immunity, epigenetics and autoimmunity in rheumatoid arthritis

The investigation of toll-like receptor 3, 9 and 10 gene polymorphisms in Turkish rheumatoid arthritis patients

Contact Info

Product

Resources

About