OBJECTIVE: Defective or inefficient DNA double-strand break (DSB) repair results 
in failure to preserve genomic integrity leading to apoptotic cell death, a 
hallmark of systemic lupus erythematosus (SLE). Compelling evidence linked 
environmental factors that increase oxidative stress with SLE risk and the 
formation of DSBs. In this study, we sought to further explore genotoxic stress 
sensitivity in SLE by investigating DSB accumulation as a marker linking the 
effect of environmental stressors and the chromatin microenvironment.
METHODS: DSBs were quantified in peripheral blood mononuclear cell subsets from 
patients with SLE, healthy controls, and patients with rheumatoid arthritis (RA) 
by measuring phosphorylated H2AX (phospho-H2AX) levels with flow cytometry. 
Phospho-H2AX levels were assessed in G0/G1, S and G2 cell-cycle phases using 
propidium iodide staining, and after oxidative stress using 0.5 µM hydrogen 
peroxide exposure for 0, 2, 5, 10, 30 and 60 min.
RESULTS: DSB levels were significantly increased in CD4+ T cells, CD8+ T cells 
and monocytes in SLE compared with healthy controls (p=2.16×10(-4), 1.68×10(-3) 
and 4.74×10(-3), respectively) and RA (p=1.05×10(-3), 1.78×10(-3) and 
2.43×10(-2), respectively). This increase in DSBs in SLE was independent of the 
cell-cycle phase, and correlated with disease activity. In CD4+ T cells, CD8+ T 
cells and monocytes, oxidative stress exposure induced significantly higher DSB 
accumulation in SLE compared with healthy controls (60 min; p=1.64×10(-6), 
8.11×10(-7) and 2.04×10(-3), respectively).
CONCLUSIONS: Our data indicate that SLE T cells and monocytes have increased 
baseline DSB levels and an increased sensitivity to acquiring DSBs in response 
to oxidative stress. Although the mechanism underlying DSB sensitivity in SLE 
requires further investigation, accumulation of DSB may serve a biomarker for 
disease activity in SLE and help explain increased apoptotic cell accumulation 
in this disease.