Circulating cell-free DNA in sickle cell disease: is it a potentially useful biomarker?
BACKGROUND
Vascular occlusion in sickle cell disease causes increased levels of plasma cell-free DNA as a result of cell death and tissue damage.


OBJECTIVE
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.


METHODS
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.
From the Department of Pathology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
Salah
S
Al-Humood
Rajaa
R
Zueriq
Lama
L
Al-Faris
Rajaa
R
Marouf
Fahd
F
Al-Mulla
D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004247:DNA / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005319:Fetal Hemoglobin / Q000378:metabolism; D006451:Hemoglobin, Sickle / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D019098:Telomerase / Q000235:genetics; D055815:Young Adult; D055544:beta-Globins / Q000235:genetics
D015415:Biomarkers; D006451:Hemoglobin, Sickle; D055544:beta-Globins; D004247:DNA; D005319:Fetal Hemoglobin; D019098:Telomerase