title: 17-β-estradiol affects BLyS serum levels and the nephritogenic autoantibody network accelerating glomerulonephritis in NZB/WF1 mice.
abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects fertile women, suggesting sex hormones are involved in disease pathogenesis. B lymphocyte stimulator (BLyS) has been found to be elevated in SLE patients and to drive a lupus-like syndrome in transgenic mice. Our aim was to evaluate the effects of estrogen administration on BLyS and nephritogenic anti-C1q and anti-dsDNA antibodies in lupus-prone NZB/WF1 mice. We implanted pellets releasing 17-β-estradiol (18.8 µg/day) on the back side the ear of 10 NZB/WF1 mice (group 1), and compared them with 10 mice intraperitoneally injected with PBS 200 μl twice a week (group 2), as controls. We evaluated BLyS, anti-dsDNA and anti-C1q serum levels starting one week after pellet implantation. We also analyzed time to proteinuria onset, proteinuria-free survival and overall survival. Kidneys, spleen, liver and lungs were harvested for histological analysis. Mice were bred until natural death. BLyS serum levels were higher in group 1 than in group 2 mice at each evaluation. Group 1 mice developed nephritogenic antibodies and proteinuria significantly earlier and at higher levels than controls. Direct correlation between BLyS and anti-C1q (R (2 )= 0.6962, p < 0.0001) or anti-dsDNA (R (2 )= 0.5953, p < 0.0001), and between anti-C1q and anti-dsDNA autoantibodies (R (2 )= 0.5615, p < 0.0001) were found. Proteinuria-free and global survival rates were significantly lower in group 1 than in controls. Histological analyses showed more severe abnormalities in group 1 mice. Estrogen administration is associated with increased levels of BLyS as well as of anti-C1q and anti-dsDNA antibodies, leading to accelerated glomerulonephritis and disease progression in NZB/WF1 mice.
authors: Division of Rheumatology, Department of Medicine-DIMED.
authors: N
authors: N
authors: Bassi
authors: Division of Surgical, Oncological, and Gastroenterological Sciences.
authors: R
authors: R
authors: Luisetto
authors: Division of Rheumatology, Department of Medicine-DIMED.
authors: A
authors: A
authors: Ghirardello
authors: Division of Rheumatology, Department of Medicine-DIMED.
authors: M
authors: M
authors: Gatto
authors: Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Italy.
authors: M
authors: M
authors: Valente
authors: Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Italy.
authors: M
authors: M
authors: Della Barbera
authors: Division of Rheumatology, Department of Medicine-DIMED.
authors: L
authors: L
authors: Nalotto
authors: Division of Rheumatology, Department of Medicine-DIMED.
authors: L
authors: L
authors: Punzi
authors: Division of Rheumatology, Department of Medicine-DIMED adoria@unipd.it.
authors: A
authors: A
authors: Doria
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D053264:B-Cell Activating Factor / Q000097:blood*; D004195:Disease Models, Animal; D018450:Disease Progression; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005921:Glomerulonephritis / Q000473:pathology*; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000150:complications*; D051379:Mice; D008814:Mice, Inbred NZB; D011507:Proteinuria / Q000652:urine
chemical_list: D001323:Autoantibodies; D053264:B-Cell Activating Factor; D004958:Estradiol
keywords: BLyS; Systemic lupus erythematosus; anti-dsDNA; estrogens; nephritis