Circulating mitochondrial DNA in serum of patients with granulomatosis with polyangiitis

Surmiak, Marcin; Hubalewska-Mazgaj, Magdalena; Wawrzycka-Adamczyk, Katarzyna; Szczeklik, Wojciech; Musiał, Jacek; Sanak, Marek

doi:10.1111/cei.12628

Cited by 31 publications

(29 citation statements)

References 29 publications

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“…The ability of mtDNA to activate proinflammatory signaling cascades links it to chronic inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and granulomatosis with polyangiitis, and atherosclerosis . For a recent review on mtDNA‐specific activation pathways see Boyapati et al., 2017 …”

Section: Np Exposure Leads To Release Of Endogenous Danger Signalsmentioning

confidence: 99%

Nanoparticles and danger signals: Oral delivery vehicles as potential disruptors of intestinal barrier homeostasis

Vita

Royse

Pullen

2019

Journal of Leukocyte Biology

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Gut immune system homeostasis involves diverse structural interactions among resident microbiota, the protective mucus layer, and a variety of cells (intestinal epithelial, lymphoid, and myeloid). Due to the substantial surface area in direct contact with an "external" environment and the diversity of xenobiotic, abiotic, and self-interactions coordinating to maintain gut homeostasis, there is enhanced potential for the generation of endogenous danger signals when this balance is lost. Here, we focus on the potential generation and reception of damage in the gut resulting from exposure to nanoparticles (NPs), common food and drug additives. Specifically, we describe recent evidence in the literature showing that certain NPs are potential generators of damage-associated molecular patterns, as well as potential immune-stimulating molecular patterns themselves. K E Y W O R D SATP, DAMP, mtDNA, NAMP, Nanoparticles, NLRP3Over the past decade, the commercial use of NPs by the food and biomedical industries has seen immense growth. The small, nanoscale size of NPs confers unique physicochemical properties that allow them to be effective oral delivery mechanisms for pharmaceuticals, food flavors, nutrient additives, and more. The accepted size range of NPs is not straightforward, varying across different biomedical and engineering disciplines and government agencies. 10,11 Although certain sources indicate that a typical NP is 1-100 nm in three dimensions, other sources consider accepted dimensions (one or more) for NPs to include <200 nm, 12 <500 nm, 13 or as large as <1000 nm. 14,15 The ASTM International definition provides for either two or three dimensions at the nanoscale, 16 whereas the ISO definition indicates nanoscale in three dimensions. 17 In an officially issued

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Section: Np Exposure Leads To Release Of Endogenous Danger Signalsmentioning

confidence: 99%

Nanoparticles and danger signals: Oral delivery vehicles as potential disruptors of intestinal barrier homeostasis

Vita

Royse

Pullen

2019

Journal of Leukocyte Biology

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“…The presence of NETs in glomeruli in AAV have then been confirmed by others (Yoshida et al 2013, O'Sullivan et al 2015, Tang et al 2015, and NETs have also been shown to be present in skin lesions (Abreu-Velez et al 2009, Sangaletti et al 2012) and thrombi , Imamoto et al 2014) from patients. In addition to the histological findings of NETs in biopsies, elevated levels of NETs in the circulations have also been identified in patients (Table I) (Kessenbrock et al 2009, Surmiak et al 2015, Surmiak et al 2016). Similar results as for NETs have been obtained for NET-associated components such as HMGB1, calprotectin, PR3, MPO, and NE as well as mtDNA when measured separately in the circulation (Table 1) (Henshaw et al 1994, Haubitz et al 1997, Ohlsson et al 2003, Wibisono et al 2010, Bruchfeld et al 2011, Pepper et al 2013, Surmiak et al 2016).…”

Section: Presence In Biopsies and Plasma/serummentioning

confidence: 98%

“…In addition to their role as antimicrobial agents, NETs of both nuclear and mitochondrial origin have been connected to autoinflammatory or autoimmune diseases (Gupta et al 2005, Kessenbrock et al 2009, Dwivedi et al 2012, Khandpur et al 2013, Leffler et al 2013, Sur Chowdhury et al 2014, Surmiak et al 2015, Lood et al 2016, and have therefore been referred to as a double edged sword of innate immunity (Kaplan and Radic 2012).…”

Section: Extracellular Trapsmentioning

confidence: 99%

“…One of these studies showed that both normal density neutrophils and LDGs in patients released more NETs than normaldensity neutrophils in HC, but also showed that LDGs appear to be the main source of NETs in the patients (Grayson et al 2015). yes (Kessenbrock et al 2009, Surmiak et al 2016 DNA + MPO or citrullinated histone 3 complexes ELISA + ) no DNA + histone complexes ELISA + (Surmiak et al 2016) no (Surmiak et al 2016) DNA PicoGreen + ) no mtDNA qPCR + (Surmiak et al 2015) yes (Surmiak et al 2015) Nuclear DNA qPCR + (Surmiak et al 2015) no (Surmiak et al 2015) PR3 ELISA/Luminex …”

Section: Presence In Biopsies and Plasma/serummentioning

confidence: 99%

“…mtDNA is also a well-known DAMP that can alert the immune system in a proinflammatory fashion (Nakahira et al 2015). Levels of mtDNA as well as NETs are elevated in various inflammatory conditions (Hajizadeh et al 2003, Cossarizza et al 2011, and of particular interest, for us, in AAV (Surmiak et al 2015). …”

Section: B and T Cells Can Release Mtdna As Et-like Structures (Webs)mentioning

confidence: 99%

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The Contribution of Innate Immunity to the Pathogenesis of ANCA-associated Vasculitis

Söderberg¹

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"Nog finns det mål och mening med vår färd -men det är vägen som är mödan värd" − Karin Boye SupervisorMårten Segelmark, Linköping University, Sweden Co-supervisorsPer Eriksson, Linköping University, Sweden Jan Ernerudh, Linköping University, Sweden Tino Kurz, Linköping University, Sweden Faculty opponentPeter Heeringa, University of Groningen, The Netherlands Abstract Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitute a group of vasculitides characterized by neutrophil-rich necrotizing inflammation of small vessels and the presence of ANCA in the circulation. Dying neutrophils surrounding the walls of small vessels are a histological hallmark of AAV. Traditionally it has been assumed that these neutrophils die by necrosis, but neutrophil extracellular traps (NETs) have recently been visualized at the sites of vasculitic lesions. NETs were first described to be involved in capture and elimination of pathogens but dysregulated production and/or clearance of NETs are thought to contribute to vessel inflammation in AAV; directly by damaging endothelial cells and indirectly by acting as a link between the innate and adaptive immune system through the generation of pathogenic PR3-ANCA and MPO-ANCA that can activate neutrophils. ANCA can, however, be found in all individuals and are therefore suggested to belong to the repertoire of natural antibodies produced by innate-like B cells, implying that not all ANCA are pathogenic.In paper I, we found neutrophils in patients to be more prone to undergo NETosis/necrosis spontaneously compared with neutrophils in healthy controls (HC), as well as that active patients possessed elevated levels of NETs in the circulation. Our results also suggest that ANCA during remission could contribute to the clearance of NETs as we observed an inverse relation between ANCA and NETs. In paper II, we observed neutrophils in patients to be more easily activated upon ANCA stimulation as they produced more ROS than neutrophils in HC. In paper III, we showed for the first time that cells of adaptive immunity (B and T cells)

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Origins, structures, and functions of circulating DNA in oncology

Thierry¹,

Messaoudi²,

Gahan³

et al. 2016

Cancer Metastasis Rev

646

604

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While various clinical applications especially in oncology are now in progress such as diagnosis, prognosis, therapy monitoring, or patient follow-up, the determination of structural characteristics of cell-free circulating DNA (cirDNA) are still being researched. Nevertheless, some specific structures have been identified and cirDNA has been shown to be composed of many “kinds.” This structural description goes hand-in-hand with the mechanisms of its origins such as apoptosis, necrosis, active release, phagocytosis, and exocytose. There are multiple structural forms of cirDNA depending upon the mechanism of release: particulate structures (exosomes, microparticles, apoptotic bodies) or macromolecular structures (nucleosomes, virtosomes/proteolipidonucleic acid complexes, DNA traps, links with serum proteins or to the cell-free membrane parts). In addition, cirDNA concerns both nuclear and/or mitochondrial DNA with both species exhibiting different structural characteristics that potentially reveal different forms of biological stability or diagnostic significance. This review focuses on the origins, structures and functional aspects that are paradoxically less well described in the literature while numerous reviews are directed to the clinical application of cirDNA. Differentiation of the various structures and better knowledge of the fate of cirDNA would considerably expand the diagnostic power of cirDNA analysis especially with regard to the patient follow-up enlarging the scope of personalized medicine. A better understanding of the subsequent fate of cirDNA would also help in deciphering its functional aspects such as their capacity for either genometastasis or their pro-inflammatory and immunological effects.

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Circulating mitochondrial DNA in serum of patients with granulomatosis with polyangiitis

Cited by 31 publications

References 29 publications

Nanoparticles and danger signals: Oral delivery vehicles as potential disruptors of intestinal barrier homeostasis

Nanoparticles and danger signals: Oral delivery vehicles as potential disruptors of intestinal barrier homeostasis

The Contribution of Innate Immunity to the Pathogenesis of ANCA-associated Vasculitis

Origins, structures, and functions of circulating DNA in oncology

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