Circulating mitochondrial DNA copy numbers represent a sensitive marker for diagnosis and monitoring of disease activity in systemic lupus erythematosus.
RMD Open
; 7(3)2021 12.
Article
em En
| MEDLINE
| ID: mdl-34916301
ABSTRACT
OBJECTIVES:
Cell-free DNA is involved in the pathogenesis of systemic lupus erythematosus (SLE) but the clinical value of cell-free DNA measurements in SLE is unknown. Our aim was therefore to examine the utility of mitochondrial (mt) DNA and nuclear (n) DNA quantification in SLE.METHODS:
EDTA plasma was drawn from 103 consecutive patients with SLE and from 56 healthy blood donors. mtDNA and nDNA copy numbers were quantified by PCR from cell-free plasma. Clinical parameters were recorded prospectively.RESULTS:
Circulating mtDNA copy numbers were increased 8.8-fold in the plasma of patients with SLE (median 6.6×107 /mL) compared with controls (median 7.6×106 /mL, p<0.0001). Among all 159 individuals, a cut-off set at 1.8×107 mtDNA copies in a receiver operated curve identified patients with SLE with 87.4% sensitivity and 94.6% specificity; the area under the curve was 0.95 (p<0.0001). mtDNA levels were independent of age or gender, but correlated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) on multivariable analysis (p=0.004). Conversely, SLEDAI was associated with prednisone dose (p<0.001), anti-double stranded DNA-titres (p=0.003) and mtDNA levels (p=0.005), but not nDNA copy numbers. In 33 patients with SLE with available follow-up, the changes of mtDNA, but not those of nDNA concentrations, robustly correlated with the evolution of the SLEDAI (r=0.55, p=0.001).CONCLUSIONS:
Circulating mtDNA unlike nDNA molecules are markedly increased in SLE plasma. Regardless of disease activity, circulating mtDNA levels distinguish patients with SLE from healthy controls with high sensitivity and represent an independent marker of SLE activity.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
DNA Mitocondrial
/
Lúpus Eritematoso Sistêmico
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
RMD Open
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
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