Increased concentrations of antibody-bound circulatory cell-free DNA in rheumatoid arthritis
Increased concentrations of antibody-bound circulatory cell-free DNA in rheumatoid arthritis
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DOI：
10.1373/clinchem.2006.084509
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发表时间：
2007-09-01
影响因子：
9.3
通讯作者：
Hasler, Paul
中科院分区：
文献类型：
--
作者：
Zhong, Xiao-Yan;von Muehlenen, Ines;Hasler, Paul
背景资料：在几种疾病中发现了游离DNA浓度的增加，并被解释为细胞死亡或更新率增加的证据。方法：采用甘油醛-3-磷酸脱氢酶（GAPDH）DNA定量PCR技术，检测类风湿关节炎（RA）患者和健康对照者血浆和血清中的游离DNA。我们使用Protein G Sepharose（TM）珠吸附血浆并洗脱以分离抗体结合的DNA。在16名健康对照的配对血浆和血清样品中，GAPDH拷贝的中位数为4500基因组当量（GE）/mL血浆26例RA患者血浆GE浓度为17000 GE/ml（21002375000，P = 0.0001）。正常人血清GAPDH拷贝数中位数为35000 GE/mL（1700239000），RA患者为222000 GE/mL（210002375000，P = 0.004）。RA中游离DNA的中位数为S1%与抗体相关，而健康对照组为9%（P = 0.001）。DNA的浓度并没有随着治疗患者的类型而变化。结论：这些结果提供了新的证据，无细胞的DNA-抗体复合物在RA的病因中的作用，提出了基础研究的新途径，并可能被证明是相关的诊断和评估治疗。(c)2007年美国临床化学协会
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 Sepharose (TM) 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 (21002 375 000, P = 0.0001). In the serum from normal controls the median GAPDH copies were 35 000 GE/mL (1700239 000) and from RA patients 222 000 GE/mL (21 0002 375 000, P = 0.004). A median of S1% 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. (c) 2007 American Association for Clinical Chemistry