Analysing cell‐free plasma DNA and SLE disease activity

Atamaniuk, Johanna; Hsiao, Yu-Yang; Mustak, Monika; Bernhard, Duhm; Erlacher, L; Födinger, Manuela; Tiran, Beate; Stuhlmeier, Karl M.

doi:10.1111/j.1365-2362.2010.02435.x

Cited by 41 publications

(42 citation statements)

References 14 publications

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“…Isolation of DNA and ICs and treatment of plasma with nucleases and proteases DNA was isolated from SLE plasma using a DNA Isolation Kit (Roche), as described previously (10). The final A260/A280 for all DNA preparations was .1.8.…”

Section: Cell Isolationmentioning

confidence: 99%

“…DNA-Ab binding and subsequent events, such as complement activation, IC deposition, and cytokine release, take place in the circulation of SLE patients (10). Accumulating studies showed that circulating DNAcontaining ICs could activate human plasmacytoid dendritic cells to induce type I IFN responses and, thus, are involved in SLE pathogenesis (11)(12)(13).…”

mentioning

confidence: 99%

“…It has been known for some time that DNA-containing immune complexes (ICs) in the circulation (termed "circulating DNA-containing ICs") are one of the hallmarks of SLE (10). DNA-Ab binding and subsequent events, such as complement activation, IC deposition, and cytokine release, take place in the circulation of SLE patients (10).…”

mentioning

confidence: 99%

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Autoantibody Induction by DNA-Containing Immune Complexes Requires HMGB1 with the TLR2/MicroRNA-155 Pathway

Wen

Lin

Chen

et al. 2013

The Journal of Immunology

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Anti-dsDNA Ab is reported to be the central pathogenic autoantibody involved in systemic lupus erythematosus (SLE) pathogenesis. However, the mechanisms involved in anti-dsDNA Ab production remain unclear. Recent evidence indicated that DNA-containing immune complexes (ICs) in circulation (termed “circulating DNA-containing ICs”), which are one of the hallmarks of SLE, might be involved in autoantibody production. In this study, we explored their potential role in anti-dsDNA Ab production and the underlying mechanisms in patients with SLE. We demonstrated that circulating DNA-containing ICs were able to induce anti-dsDNA Ab. Of note, HMGB1 in circulating DNA-containing ICs was crucial for anti-dsDNA Ab induction. The HMGB1 content of circulating DNA-containing ICs also correlated positively with anti-dsDNA Ab production in patients with SLE. Further, we revealed that the TLR2/MyD88/microRNA-155 (miR-155) pathway was pivotal for HMGB1 to confer anti-dsDNA Ab induction, and Ets-1 was a functional target of miR-155 in the induction of anti-dsDNA Ab by circulating DNA-containing ICs. Finally, we validated the expression of miR-155 and Ets-1 and their correlation with anti-dsDNA Ab production in patients with SLE. To our knowledge, this is the first report of the crucial role of HMGB1 in autoantibody production mediated by the TLR2/MyD88/miR-155/Ets-1 pathway. These findings identify a novel mechanism to account for the persistent production of anti-dsDNA Ab in SLE and a clue for developing a novel therapeutic strategy against SLE.

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Section: Cell Isolationmentioning

confidence: 99%

mentioning

confidence: 99%

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Autoantibody Induction by DNA-Containing Immune Complexes Requires HMGB1 with the TLR2/MicroRNA-155 Pathway

Wen

Lin

Chen

et al. 2013

The Journal of Immunology

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“…While some of them reported correlation of cfDNA levels with disease activity or relationship with unfavorable outcome in situations like systemic sclerosis, experimental pulmonary thromboembolism, severe sepsis or intensive care unit patients; such a study done in SLE patients revealed not very promising results [22][23][24][25][26]. Atamaniuk et al [26] in their research measuring the levels of circulating DNA as a potential tool to assess and to predict disease activity in patients with SLE indicated that cfD-NA plasma levels in patients with SLE were significantly increased. The authors stated that especially apoptosis and necrosis would lead to an increase in measurable free plasma DNA, however they found no correlation between cfDNA levels and SLE activity.…”

Section: Discussionmentioning

confidence: 99%

Plasma Cell-free DNA levels in children with Henoch Schönlein purpura

Bek¹,

Özkaya²,

Acikgoz³

et al. 2014

Turk J Bioch

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Objective: Circulating free nucleic acids are found at low levels in healthy subjects and in some diseases. The source is reported to be apoptosis of lymphocytes and other nucleated cells. The aim of this study is to investigate cfDNA levels in children with Henoch Schönlein purpura (HSP) during acute and remission phases. Methods: We investigated cfDNA levels in 21 children with HSP in acute phase and 21 in remission and in 25 healthy controls using real-time quantitative PCR. Results: We found significantly increased cfDNA levels in acute HSP patients (median: 6632.5 pg/ml) compared to those in remission (4540.8 pg/ml) and healthy controls (4650 pg/ml) (p<0.05). Conclusion: Significantly increased cfDNA levels in acute phase of HSP might be explained by increased apoptosis. Measuring cfDNA levels may have a potential role for monitoring HSP activity. For this finding, determination of complex interactions at cellular level and prognostic significance need further research. Key Words: Apoptosis, cell-free DNA, Henoch-Schönlein purpura, children Plasma. Conflict of Interest:The authors declare no conflict of interest. ÖZETAmaç: Sağlıklı bireylerde ve bazı hastalık durumlarında dolaşımda serbest nükleik asitler bulunurlar. Bu nükleik asitlerin kaynağının lenfosit ve diğer çekirdekli hücrelerin apoptozisi olduğu bildirilmektedir. Bu çalışmada Henoch Schönlein purpuralı (HSP) çocuklarda akut hastalık ve remisyon fazlarında plazma serbest nükleik asit (cfDNA) düzeylerinin araştırılması amaçlan-mıştır. Metod: Gerçek-zamanlı kantitatif PCR yöntemi kullanarak 21 akut, 21 remisyonda olan HSP li çocuk ve 25 sağlıklı kontrolde plazma cfDNA düzeylerini araştırdık. Bulgular: Akut HSP hastalarında cfDNA düzeylerini (medyan: 6632.5 pg/ml) remisyondaki (4540.8 pg/ml) ve sağlıklı kontrollerdeki (4650 pg/ml) düzeylere göre istatistiksel olarak anlamlı düzeyde yüksek bulduk (p<0.05). Sonuç: Akut HSP'li çocuklarda cfDNA düzeylerinin anlamlı düzeyde yüksek bulunması bu hastalardaki artmış apoptotik aktivite ile açıklanabilir. Hastalık aktivitesinin izleminde cfDNA ölçümünün potansiyel bir rolü olabilir. Bu bulgunun hücresel düzeydeki karmaşık etkileşimle-rinin ve prognostik öneminin belirlenmesi için ileri çalışmalara gereksinim vardır. Anahtar Kelimeler: Apoptozis, serbest nükleik asitler, Henoch-Schönlein Purpura, çocuklar. Çıkar Çatışması: Yazarların çıkar çatışması yoktur.

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“…In the late 1990s (after the landmark papers by Chen et al [12] and Nawroz et al [13] were published) this observation initiated a surge of papers confirming and extending the results described by Leon et al Unfortunately, it became clear very soon that the increase in cfDNA in tumor patients is not specific and that many factors/diseases lead to the higher quantity of cfDNA (see chapter "The Biology of CNAPS"). When cfDNA had been quantified it was shown that the amount is increased in a variety of different conditions such as myocardial infarction [14], cardiac arrest [15], exhaustive exercise [16][17][18], in patients with systemic lupus erythematosis [19], in older humans [20], in febrile patients [21], in children on peritoneal dialysis [22], in patients with obstructive sleep apnea [23], patients with chronic kidney disease [24], patients with severe sepsis or septic shock [25], in trauma [26] and burn patients [27] (chapter "CNAPS and General Medicine"). In an attempt to differentiate lung cancer patients from a control population according to their sputum cfDNA it was demonstrated that the amount of cfDNA was related to the severity of the inflammatory processes but not the presence of lung cancer [28].…”

Section: Dna Quantification/dna Integritymentioning

confidence: 99%

Extracellular Nucleic Acids and Cancer

Fleischhacker¹,

Schmidt²

2014

Advances in Predictive, Preventive and Personalised Medicine

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Since the clear proof of the presence of tumor-associated genetic alterations in extracellular nucleic acids almost 20 years ago this field gained has attracted much interest. According to our current knowledge it seems as if all tumor-associated alterations found in tumor cells are also found in the extracellular environment. The isolation of extracellular nucleic acids from tumor patients and its genetic characterization with very sensitive and highly specific methods led to the concept of "liquid biopsy". This means that for follow-up analysis of tumor patients, the physicians no longer depend exclusively on a single examination of tissue biopsies (usually at the time of diagnosis) but are able by longitudinally analyzing the extracellular nucleic acids to follow the reaction of a tumor to e.g. a given therapy, the development of resistance mechanisms. In this chapter we will discuss the detection and characterization of different genetic (e.g. mutation analysis and structural variations as seen in microsatellites), epigenetic (e.g. hypermethylation of selected sequences) and regulatory alterations (as in different miRNA expression patterns found in tumor patients). We will also touch on some confounding factors that have to be taken into consideration as well as the functional and biological aspects of extracellular nucleic acids.

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Analysing cell‐free plasma DNA and SLE disease activity

Abstract: The presented data seem to exclude measuring free plasma DNA as an inexpensive, simple and quick tool to assess disease activity in patients with SLE. Further studies on a larger patient population would be needed to confirm our results.

Cited by 41 publications

References 14 publications

Autoantibody Induction by DNA-Containing Immune Complexes Requires HMGB1 with the TLR2/MicroRNA-155 Pathway

Autoantibody Induction by DNA-Containing Immune Complexes Requires HMGB1 with the TLR2/MicroRNA-155 Pathway

Plasma Cell-free DNA levels in children with Henoch Schönlein purpura

Extracellular Nucleic Acids and Cancer

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