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Nuclear and Mitochondrial Circulating Cell-Free DNA Is Increased in Patients With Inflammatory Bowel Disease in
Zuzana Vrablicova1, Kristina Tomova2, Lubomira Tothova3
15th Department of Internal Medicine, Sub-department of Gastroenterology and Hepatology, Faculty of Medicine, Comenius University, University Hospital Bratislava, Bratislava, Slovakia.
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.
Insights
Inflammatory bowel disease (IBD) patients show elevated nuclear DNA (ncDNA) and mitochondrial DNA (mtDNA) levels, even in remission. Sex differences in ncDNA levels may be linked to reduced deoxyribonuclease (DNase) activity in males.
Area of Science:
- Genetics
- Immunology
- Biochemistry
Background:
- Emerging evidence suggests a role for cell-free DNA (cfDNA) in inflammatory bowel disease (IBD) pathogenesis.
- Investigating cfDNA and deoxyribonuclease (DNase) activity in IBD patients during clinical remission is crucial.
Purpose of the Study:
- To analyze circulating cfDNA (total, nuclear DNA (ncDNA), and mitochondrial DNA (mtDNA)) and DNase activity in IBD patients in clinical remission.
- To explore potential sex differences in cfDNA levels and their association with DNase activity.
Main Methods:
- Plasma and serum samples were collected from 72 Crohn's disease and 28 ulcerative colitis patients.
- Quantification of total cfDNA, ncDNA, mtDNA, and measurement of DNase activity were performed.
Main Results:
- IBD patients exhibited significantly higher levels of both ncDNA and mtDNA compared to healthy controls.
- Males had higher ncDNA concentrations than females across both patient and control groups.
- Female IBD patients showed higher ncDNA levels than female controls, while male IBD patients had lower DNase activity and a negative correlation between DNase activity and ncDNA levels.
Conclusions:
- Circulating ncDNA and mtDNA are increased in IBD patients in clinical remission.
- ncDNA and mtDNA may not be optimal biomarkers for IBD disease activity.
- The study highlights the first reported sex difference in circulating ncDNA levels, potentially linked to reduced DNase activity in males.
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