Oxidative stress and Treg depletion in lupus patients with anti-phospholipid syndrome

Anti-phospholipid antibodies (APLA) represent a diagnostic criterion of systemic lupus erythematosus (SLE) and cause morbidity, termed anti-phospholipid syndrome (APS). Activation of the mechanistic target of rapamycin (mTOR) has been recently associated with APS. mTOR is a sensor of oxidative stress. Therefore, we examined mitochondrial mass, superoxide production, mTOR activity and FoxP3 expression in 72 SLE patients, twelve of whom also had APS, and 54 healthy controls by flow cytometry. Mitochondrial mass was increased in CD4(-)CD8(-) double-negative (DN) T cells of SLE patients with APS (2.7-fold) in comparison to those without APS (1.7-fold; p = 0.014). Superoxide production was increased in all lymphocyte subsets of APS patients. FoxP3(+) cells were depleted within CD4(+)CD25(+) Tregs in patients with APS (28.4%) relative to those without APS (46.3%, p = 0.008). mTOR activity was similar between SLE patients with and without APS. Thus, oxidative stress and Treg depletion rather than mTOR activation underlie APS in patients with SLE.