Nuclear and Mitochondrial Circulating Cell-Free DNA Is Increased in Patients With Inflammatory Bowel Disease in Clinical Remission

Abstract

Background: The role of cell-free DNA (cfDNA) in the pathogenesis of inflammatory bowel disease (IBD) has been recently suggested. The aim of this study was to analyze circulating cfDNA and deoxyribonuclease (DNase) activity in IBD patients in clinical remission.Materials and Methods: Plasma and serum were obtained from 72 patients with Crohn's disease and 28 patients with ulcerative colitis. Total cfDNA, nuclear DNA (ncDNA), mitochondrial DNA (mtDNA) and DNase activity were measured.Results: IBD patients showed higher levels of both ncDNA and mtDNA compared to healthy controls. Concentration of ncDNA was higher in males compared to females, including patients and healthy controls. However, unlike males higher amount of ncDNA was found in female IBD patients compared to healthy controls. DNase activity was significantly lower in male IBD patients compared with healthy controls. In addition, there was a negative correlation between DNase activity and ncDNA levels in male IBD patients.Conclusions: Herein we present increased amount of circulating ncDNA and mtDNA in IBD patients in clinical remission. Thus, unlike total cfDNA, circulating ncDNA and mtDNA might not represent the optimal biomarkers of disease activity. This is also the first report on sex difference in circulating ncDNA levels, possibly associated with lower DNase activity in males.

Circulating extracellular DNA is in association with continuous metabolic syndrome score in healthy adolescents

“…A vicious circle involving activation of immune cells that produce ecDNA activating other immune cells explains partially the pathomechanism of sepsis or hepatorenal injury (12,13). However, a similar mechanism could be involved in the pathogenesis of chronic sterile inflammation, as recently shown for inflammatory bowel diseases (14).…”

Machine learning-based detection of immune-mediated diseases from genome-wide cell-free DNA sequencing datasets

“…Increased levels of cell-free DNA (cfDNA) have been observed in individuals with systemic lupus erythematosus (SLE), a common and prototypical autoimmune disease (AID), as early as the 1960s 1 . The elevation of cfDNA has been found in other AID, such as rheumatoid arthritis (RA) 2 and inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC) 3 , 4 . Despite the existence of different predictive and prognostic biomarkers for AID and IBD, more robust non-invasive markers to deliver precision medicine are needed 5 , 6 .…”

Circulating mitochondrial cell-free DNA dynamics in patients with mycobacterial pulmonary infections: Potential for a novel biomarker of disease

“…For plasma preparation, 8–10 mL of whole blood was collected with K2-EDTA Vacutainer tubes (BD, Franklin Lakes, NJ, USA) and centrifuged for 10 minutes at 1500 rpm within 2 hours of collection ( 29 ). Using the QIAamp DNA Blood Mini Kit (Qiagen, Hilden, Germany), cfDNA was extracted from a 400 µL plasma sample with an elution volume of 50 µL and stored in a microcentrifuge tube at −80°C until real-time quantitative polymerase chain reaction (qPCR) was performed in batches ( 30 , 31 ).…”