title: Oxidative stress and Treg depletion in lupus patients with anti-phospholipid syndrome.
abstract: 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.
authors: Division of Rheumatology, Department of Medicine, State University of New York Upstate Medical University, College of Medicine, Syracuse, NY 13210, USA; Department of Microbiology and Immunology, State University of New York Upstate Medical University, College of Medicine, Syracuse, NY 13210, USA.
authors: Zhi-wei
authors: ZW
authors: Lai
authors: Division of Rheumatology, Department of Medicine, State University of New York Upstate Medical University, College of Medicine, Syracuse, NY 13210, USA; Department of Microbiology and Immunology, State University of New York Upstate Medical University, College of Medicine, Syracuse, NY 13210, USA.
authors: Ivan
authors: I
authors: Marchena-Mendez
authors: Division of Rheumatology, Department of Medicine, State University of New York Upstate Medical University, College of Medicine, Syracuse, NY 13210, USA; Department of Microbiology and Immunology, State University of New York Upstate Medical University, College of Medicine, Syracuse, NY 13210, USA. Electronic address: perla@upstate.edu.
authors: Andras
authors: A
authors: Perl
mesh_terms: D000328:Adult; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000378:metabolism*; D015415:Biomarkers; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000378:metabolism*; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: Anti-phospholipid syndrome; Mechanistic target of rapamycin; Oxidative stress; Systemic lupus erythematosus; Treg; mTOR