Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.

Circulating Mitochondrial DNA Copy Numbers As a Highly Sensitive Diagnostic Marker of Systemic Lupus Erythematosus and An Independent Predictor of SLE Activity.

Venhoff¹, Nils, Thiel¹, Jens, Lebrecht¹, Dirk, Foocharoen², Chingching, Effelsberg¹, Nora M., Trendelenburg³, Marten, Hasler⁴, Paul

Dept. of Rheumatology and Centre of Chronic Immunodeficiency, University of Freiburg, Freiburg, Germany
Dept. of Rheumatology at Basel University, Felix-Platter Spital, Basel, Switzerland
Dept. of Internal Medicine, University Hospital Basel, Basel, Switzerland
Dept. of Rheumatology, Kantonsspital Aarau, Aarau, Switzerland

Background/Purpose:

Toll-like receptor (TLR) 9 signaling is important in the pathogenesis of systemic lupus erythematosus (SLE) and its type I interferon signature. TLR9 recognizes dsDNA which may be released by neutrophil extracellular traps (NETs) upon stimulation by tissue injury. This study examines if the quantitative analysis of two dsDNA species, namely circulating mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) may contribute to the understanding of SLE, be useful in the clinical diagnosis of SLE and the monitoring of its disease activity.

Methods:

77 SLE patients (mean age 46.2 years, 65 females, median disease duration 6.1 years, 43% with a history of lupus nephritis) and 40 controls (healthy volunteers, or persons hospitalized for osteoarthritis or herniated intervertebral disks, mean age 44.2 years, range 20–95 years, 23 females) from two tertiary care centers were included in this cross-sectional study. MtDNA and nDNA copy numbers in plasma were quantified by PCR. SLE activity was determined by means of the SLEDAI. C-reactive protein (CRP), C3, C4 and C3d-levels, as well as autoantibody titers against dsDNA, phospholipids, SSA, SSB, and proteinuria were quantified at the time of blood collection.

Results:

Circulating mtDNA copy numbers in the plasma of SLE patients were increased by a factor of 82 (median 1,356,667/mL; interquartile range (IQR) 844,667–2,346,667) compared to controls (median 16,500/mL; IQR 11,275–33,816) (p<0.001). None of the SLE patients had mtDNA copies below the highest control value (113,667/mL). Circulating mtDNA-levels were not dependent on age or gender, but correlated with anti-dsDNA titers (R²=0.17, p<0.001), C3d (R²=0.21, p<0.001), C4 levels (R²=0.06, p=0.05), CRP (R²=0.06, p=0.03), and SLEDAI (R²=0.31, p<0.001) on univariate analysis. In multivariate analysis, only C3d (p=0.04), and SLEDAI (p=0.03) remained predictive for the mtDNA-levels.

Conversely SLEDAI was predicted on multivariate analysis by mtDNA-levels (p=0.001), anti-dsDNA-antibodies (p=0.03), and CRP (p<0.001). Circulating nDNA copy numbers were low in both controls (7170/mL, IQR 3203.5–18170) and SLE patients (13,607/mL, IQR 4,567–33,933, p=0.07) and did not correlate with any covariate in SLE.

Figure 1. Circulating mtDNA copy numbers in plasma of SLE patients and control persons. Error bars represent IQR, individual points represent outliers.

Conclusion:

Circulating mtDNA, unlike nDNA molecules, are markedly increased in SLE plasma. Regardless of disease activity circulating mtDNA-levels distinguish SLE patients from non-inflammatory controls with high sensitivity. In addition, circulating mtDNA copies represent an independent marker of SLE disease activity.

To cite this abstract, please use the following information:
Venhoff, Nils, Thiel, Jens, Lebrecht, Dirk, Foocharoen, Chingching, Effelsberg, Nora M., Trendelenburg, Marten, et al; Circulating Mitochondrial DNA Copy Numbers As a Highly Sensitive Diagnostic Marker of Systemic Lupus Erythematosus and An Independent Predictor of SLE Activity. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2600
DOI:

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