PLASMA MITOCHONDRIAL DNA AS A BIOMARKER IN DIAGNOSIS AND FOLLOW-UP OF SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: S. Giaglis et al.
Mitochondrial DNA (mtDNA) participates in the formation of neutrophil extracellular traps (NETs), is interferogenic, and causes disease in lupus models. The diagnostic and prognostic value of cell-free DNA in human SLE is however still unknown. The aim of this study was therefore to examine the clinical utility of cell-free DNA measurements as a non-invasive biomarker in SLE.
Cell free DNA was quantified by PCR from the plasma of 56 healthy controls and 103 SLE patients. mtDNA levels were significantly elevated in SLE plasma (1.3×10 8 copies/ml plasma), compared to HC plasma (8.6×10 6 copies/ml plasma, p<0.0001, whereas nDNA levels did not differ. Receiver operating characteristic curve analysis showed that mtDNA copy numbers differentiated between SLE and HC with 87.4% sensitivity and 94.6% specificity (Figure).
mtDNA levels correlated with the SLE Activity at baseline. In 32 SLE patients with follow-up, delta mtDNA-levels also robustly correlated with changes in SLE activity (Figure).
(a) Receiver operating characteristic curve for mtDNA plasma concentrations to discriminate between HC and SLE patients. (b) In SLE patients, the changes in plasma mtDNA levels at follow-up correlate with the evolution of SLE activity.
Targeting B-cells dually by the RTX/BEL drug combination demonstrated a trend towards improved pSS activity and salivary flow, along with B-cell depletion in minor salivary gland biopsies. Larger studies must determine if patients benefit long-term in this difficult-to-treat connective tissue disease.