Circulating Cell-Free DNA in Sickle Cell Disease: Is It a Potentially Useful Biomarker?

Abstract

Context.—Vascular occlusion in sickle cell disease causes increased levels of plasma cell-free DNA as a result of cell death and tissue damage. Objectives.—This study investigates plasma cell-free DNA concentrations in sickle cell disease patients, and aims at exploring the significance of plasma cell-free DNA as a potential biomarker in predicting its complications. Design.—Plasma cell-free DNA levels were measured using real-time quantitative polymerase chain reaction to quantitatively measure β-globin gene in blood samples from 57 sickle cell disease patients with acute vaso-occlusive crisis, 42 patients in steady state, 16 individuals with sickle cell trait, and 40 healthy controls. Results.—Plasma cell-free DNA level was significantly elevated in samples from patients with acute vaso-occlusive crisis when compared with those in steady state (P = .002), and was significantly higher both in crisis and in steady state when compared with individuals with sickle cell trait and healthy controls (P < .001). There was no difference in cell-free DNA levels between individuals with sickle cell trait and healthy controls. There was no association between plasma cell-free DNA levels and various clinical complications of sickle cell disease and comorbidity. Conclusions.—Plasma cell-free DNA, as quantified by polymerase chain reaction amplification of the β-globin and human telomerase reverse transcriptase genes, is increased in sickle cell disease patients in vaso-occlusive crisis and in steady state compared with individuals with sickle cell trait and healthy controls, and may be used as a tool to diagnose and monitor the sickle cell crisis and differentiate post–packed red cell transfusion sickle cell disease patients from individuals with sickle cell trait.

Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 Axis

“…The circulating cell-free DNA in SCA patients even at steady state can be recognized by TLR9 [61,62]. Perhaps in Journal of Immunology Research our SCA patients at steady state, the hemolysis process and the release of heme are contained, not releasing sufficiently high concentrations to induce upregulation of TLRs 2 and 4, however sufficient to induce TLR9 expression.…”

Quantification of cell-free DNA for evaluating genotoxic damage from occupational exposure to car paints

“…These results are in agreement with previous studies where wide variability in the mean of cfDNA concentrations was also observed [ 7 , 28 , 29 ]. It should be noted also that the kinetics of genotoxic damage-related cfDNA release into the bloodstream and its subsequent clearance have not yet elucidated [ 30 ] thus making the cfDNA, as rightly Danese et al said, a “hard to read” analyte [ 31 ].…”

Coagulation abnormalities of sickle cell disease: Relationship with clinical outcomes and the effect of disease modifying therapies

“…Polyphosphates may be released by activated platelets (55) and an increased number of circulating microparticles are described in SCD (see below). In addition, increased levels of cell-free DNA and nucleosomes released by activated neutrophils, and possibly other cells, have been detected in the plasma of SCD patients at “steady state,” with accentuated levels during acute painful episodes and acute chest syndrome (56–58). Kininogen deficient mice transplanted with bone marrow from Townes sickle mice show lower levels of plasma TAT compared to normal kininogen littermates (59).…”