title: Circulating mitochondrial DNA in serum of patients with granulomatosis with polyangiitis.
abstract: Neutrophil is a key cell in pathophysiology of granulomatosis with polyangiitis. Recently, neutrophil extracellular traps were described in this disease. Mitochondrial DNA is also released during traps formation. We measured circulating cell-free mitochondrial and genomic DNA in serum of patients with granulomatosis with polyangiitis. Subjects with the disease (14 active and 11 in remission stage) and 10 healthy controls were enrolled. Quantitative real-time polymerase chain reaction (PCR) was used to measure 79 base pairs (bp) and 230 bp mtDNA fragments. Alu repeats were quantified to evaluate abundance of nuclear DNA in serum at the presence of plasmid control. Both fragments of mtDNA (79 bp and 230 bp) and genomic DNA were elevated significantly in granulomatosis with polyangiitis compared to controls. Only the shorter 79 bp mtDNA correlated with active stage of granulomatosis with polyangiitis and clinical symptoms. A mechanism of extracellular release of mitochondrial DNA accompanies the active stage of the disease. Circulating mtDNA is extremely high in untreated patients. This suggests that biomarker properties of mtDNA are useful for monitoring of treatment.
authors.affiliation: Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: M P
authors.identifier: http://orcid.org/0000-0001-8396-1488
authors.initials: MP
authors.lastname: Surmiak
authors.affiliation: Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Hubalewska-Mazgaj
authors.affiliation: Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Wawrzycka-Adamczyk
authors.affiliation: Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Szczeklik
authors.affiliation: Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Musiał
authors.affiliation: Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Sanak
mesh_terms: D015415:Biomarkers / Q000097:blood; D004272:DNA, Mitochondrial / Q000097:blood*; D065206:Extracellular Traps / Q000276:immunology; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000097:blood* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D009504:Neutrophils / Q000276:immunology
chemical_list: D015415:Biomarkers; D004272:DNA, Mitochondrial
keywords: GPA; circulating mtDNA; real-time PCR