Cell-Free Nucleic Acids and their Emerging Role in the Pathogenesis and Clinical Management of Inflammatory Bowel Disease

Int J Mol Sci. 2019 Jul 26;20(15):3662. doi: 10.3390/ijms20153662.


Cell-free nucleic acids (cfNAs) are defined as any nucleic acids that are present outside the cell. They represent valuable biomarkers in various diagnostic protocols such as prenatal diagnostics, the detection of cancer, and cardiovascular or autoimmune diseases. However, in the current literature, little is known about their implication in inflammatory bowel disease (IBD). IBD is a group of multifactorial, autoimmune, and debilitating diseases with increasing incidence worldwide. Despite extensive research, their etiology and exact pathogenesis is still unclear. Since cfNAs were observed in other autoimmune diseases and appear to be relevant in inflammatory processes, their role in the pathogenesis of IBD has also been suggested. This review provides a summary of knowledge from the available literature about cfDNA and cfRNA and the structures involving them such as exosomes and neutrophil extracellular traps and their association with IBD. Current studies showed the promise of cfNAs in the management of IBD not only as biomarkers distinguishing patients from healthy people and differentiating active from inactive disease state, but also as a potential therapeutic target. However, the detailed biological characteristics of cfNAs need to be fully elucidated in future experimental and clinical studies.

Keywords: NETosis; cell-free DNAs; cell-free RNAs; cell-free nucleic acids; circulating nucleic acids; exosomes; inflammatory bowel disease; neutrophil extracellular traps.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Cell-Free Nucleic Acids*
  • DNA, Mitochondrial
  • Disease Management
  • Disease Susceptibility*
  • Exosomes
  • Extracellular Traps
  • Humans
  • Inflammatory Bowel Diseases / diagnosis
  • Inflammatory Bowel Diseases / etiology*
  • Inflammatory Bowel Diseases / metabolism*
  • Inflammatory Bowel Diseases / therapy
  • Molecular Targeted Therapy
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Neutrophils / pathology
  • RNA, Long Noncoding / genetics


  • Biomarkers
  • Cell-Free Nucleic Acids
  • DNA, Mitochondrial
  • RNA, Long Noncoding