Cell‐surface‐bound circulating DNA in the blood: Biology and clinical application

Abstract

Cell‐surface‐bound extracellular DNA (csbDNA) is present on the outer membrane of blood cells, including both red blood cells and leukocytes. Although less well characterized than cell‐free DNA (cfDNA) in plasma and serum, leukocyte and red blood cell csbDNA form a considerable fraction of the blood extracellular nucleic acids pool, with typically at least comparable amount of DNA occurring bound to the outer surface of cells as compared with circulating free DNA in plasma. The cellular origin of csbDNA is not clear; however, as with cfDNA, in patients with cancer a proportion is derived from the tumor, thus making it potentially a useful source of DNA for cancer diagnosis, prognosis, and monitoring. © 2019 IUBMB Life, 71(9):1201–1210, 2019

Autoimmune anti-DNA and anti-phosphatidylserine antibodies predict development of severe COVID-19

“…Our study is focused on two specific autoantibodies, anti-DNA and anti-PS, because of their previously described roles in the pathogenesis of other diseases ( Pisetsky & Lipsky, 2020 ; Rivera-Correa & Rodriguez, 2020 ) and their capacity to bind to different cell types in the circulation ( Fernandez-Arias et al, 2016 ; Tamkovich & Laktionov, 2019 ). We observed that anti-DNA antibodies, which are typically found in autoimmune disorders, such as SLE ( Pisetsky, 2016 ) and in some infectious diseases ( Berlin et al, 2007 ), are found in 6% of COVID-19 patients in this cohort and correlate strongly with severity of COVID-19 disease in this group.…”

“…Because the levels of cell-free DNA and anti-DNA correlate with severity of disease and markers of cell injury, it is likely that the binding of anti-DNA to cell-free DNA contributes to the pathogenesis of COVID-19 manifestations. It is known that cell-free DNA binds to the surface of endothelial and immune cells (Tamkovich & Laktionov, 2019), as well as erythrocytes (Hotz et al, 2018), where it could constitute a target for anti-DNA antibodies in the circulation, triggering complement-mediated cell lysis. We observed a strong correlation of anti-DNA antibodies with lactate dehydrogenase (LDH) and creatine kinase, suggesting that anti-DNA antibodies may contribute to muscle injury, which is frequent in COVID-19 patients (Paliwal et al, 2020).…”

Autoimmune anti-DNA antibodies predict disease severity in COVID-19 patients

“…Our study is focused on two specific autoantibodies, anti-DNA and anti-PS, because of their previously described roles in the pathogenesis of other diseases (14, 15) and their capacity to bind to different cell types in the circulation (18, 19). We observed that anti-DNA antibodies, which are typically found in autoimmune disorders, such as Systemic Lupus Erythematosus (20) and in some infectious diseases (21), are found in 13% of COVID-19 patients in this cohort and correlate strongly with severity of COVID-19 disease in this group.…”

“…It is known that cell-free DNA binds to the surface of endothelial and immune cells (19), as well as erythrocytes (23), where it could constitute a target for anti-DNA antibodies in the circulation, triggering complement-mediated cell lysis. We observed a strong correlation of anti-DNA antibodies with lactate dehydrogenase (LDH) and creatine kinase, suggesting that anti-DNA antibodies may contribute to muscle injury, which is frequent in COVID-19 patients (24).…”

Application of Data Science in Circulating Tumor DNA Detection: A Promising Avenue Towards Liquid Biopsy

“…The enriched mitochondrial ctDNA is about 100 bp in size, much smaller than that of nuclear ctDNA, further displaying the size variety of ctDNA fragments ( 8 ). Notably, there are long-size cfDNA fragments that exist, such as 2 kb and 20 kb fragments, which are probably generated from cancer cell necrosis ( 25 ) and blood cell surface ( 26 ), respectively. The accurate enrichment of ctDNA in a particular interval size eliminates some background noises to some extent and relatively enhances data processing efficiency.…”