Circulating DNA: a potential marker of sickle cell crisis.
Free circulating DNA is present in the plasma of healthy subjects, and is elevated in conditions characterized by increased cell death, such as cancer and physical trauma. Analysis of circulating DNA in plasma could provide a useful biomarker in sickle cell disease (SCD) in view of the increased cell turnover through chronic ongoing haemolysis, recurrent vaso-occlusion and inflammation. Plasma DNA was determined by real-time quantitative polymerase chain reaction (PCR) amplification of the beta-globin gene (HBB) in 154 patients with SCD [105 haemoglobin (Hb)SS, 46 HbSC and three HbS/beta(0) thalassaemia] and 53 ethnically matched controls. Blood samples were obtained from all patients in steady state; 21 of the 154 patients were also sampled during admission to hospital for acute pain. Median concentration of circulating plasma DNA in acute pain was more than 10-fold that in steady state and in controls - 10070 vs. 841 and 10070 vs. 933 genome equivalents/ml respectively (P < 0.0001, in both cases). During steady state, patients had plasma DNA levels similar to controls. Plasma DNA levels in SCD correlated with C-reactive protein levels (P < 0.005) and total white cell counts (P < 0.05) in steady state. The study shows that plasma DNA concentration may have potential as a biomarker in sickle cell patients.
Vasavda
Nisha
N
King's College London, King's College Hospital, Division of Gene and Cell Based Therapy, Denmark Hill, London, UK.
Ulug
Pinar
P
Kondaveeti
Sheila
S
Ramasamy
Karthik
K
Sugai
Taku
T
Cheung
Gordon
G
Rees
David C
DC
Awogbade
Moji
M
Bannister
Sybil
S
Cunningham
Juliette
J
Menzel
Stephan
S
Thein
Swee Lay
SL
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D004247:DNA / Q000097:blood*; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; D002097:C-Reactive Protein; D004247:DNA