title: Interferon alpha on NZM2328.Lc1R27: enhancing autoimmunity and immune complex-mediated glomerulonephritis without end stage renal failure.
abstract: Interferon alpha (IFNα) may play a significant role in systemic lupus erythematosus (SLE) pathogenesis. Recent literature suggests that IFNα does not correlate with disease activities and blockade of IFNα is not effective in treating SLE. This study aims to delineate further the role of IFNα in SLE. 12-week old NZM2328 and its congenic NZM2328.Lc1R27 (R27) female mice were challenged with adenovirus-IFNα (adeno-IFNα) or adenovirus-LacZ (adeno-LacZ). Only adeno-IFNα treated NZM2328 developed severe proteinuria and died of chronic glomerulonephritis (GN) and end stage renal disease. Adeno-IFNα treated R27 did develop immune complex-mediated GN but had normal renal function. Adeno-LacZ treated NZM2328 showed enlarged glomeruli and increased cellularity without immune complex deposition. Adeno-LacZ treated R27 did not show serological and histological abnormalities. Adeno-IFNα induced anti-dsDNA and anti-kidney autoantibodies in NZM2328 and R27. These results suggest that end organ damage is host-dependent and less related to autoimmunity and may have significant implications in SLE pathogenesis.
authors: Center for Immunity, Inflammation and Regenerative Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
authors: Chao
authors: C
authors: Dai
authors: Center for Immunity, Inflammation and Regenerative Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
authors: Hongyang
authors: H
authors: Wang
authors: Center for Immunity, Inflammation and Regenerative Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
authors: Sun-Sang J
authors: SS
authors: Sung
authors: Center for Immunity, Inflammation and Regenerative Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
authors: Rahul
authors: R
authors: Sharma
authors: Center for Immunity, Inflammation and Regenerative Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
authors: Carol
authors: C
authors: Kannapell
authors: Center for Immunity, Inflammation and Regenerative Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
authors: Wei
authors: W
authors: Han
authors: Center for Immunity, Inflammation and Regenerative Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
authors: Qian
authors: Q
authors: Wang
authors: Center for Autoimmunity and Musculoskeletal Diseases, Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors: Anne
authors: A
authors: Davidson
authors: Department of Psychiatry and Neurobehavioral Sciences, School of Medicine, University of Virginia, Charlottesville, VA, USA.
authors: Felicia
authors: F
authors: Gaskin
authors: Center for Immunity, Inflammation and Regenerative Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, USA; Division of Rheumatology, Department of Medicine, University of Virginia, Charlottesville, VA, USA; Department of Microbiology, Immunology and Cancer Biology, School of Medicine, University of Virginia, Charlottesville, VA, USA. Electronic address: sf2e@virginia.edu.
authors: Shu Man
authors: SM
authors: Fu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000276:immunology* / Q000503:physiopathology; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology*; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000503:physiopathology; D008181:Lupus Nephritis / Q000276:immunology*; D051379:Mice
chemical_list: D016898:Interferon-alpha
keywords: Interferon α; Mouse model for lupus nephritis; SLE