title: Nephritogenic-antinephritogenic antibody network in lupus glomerulonephritis.
abstract: Lupus glomerulonephritis (LGN) is one of the most threatening manifestations of systemic lupus erythematosus (SLE) and a major predictor of poor prognosis. The mechanisms leading to kidney inflammation are not completely clear; however, autoantibodies seem to play a pivotal role. Apoptosis dysregulation in SLE is likely to trigger generation of autoantibodies, the released nucleosomes being the driving autoantigen for further epitope amplification and selection of DNA or nucleosome-specific B cells. Growing evidence supports a multistep path to LGN involving initial autoantibody binding to chromatin fragments in the mesangial matrix, where they can induce mesangial inflammation leading to a shut-down of the renal DNase gene, generation and deposition of secondary necrotic chromatin on the glomerular basement membrane favouring antibody binding, complement activation and development of membrano-proliferative glomerular lesions. Anti-DNA IgG antibodies display the major pathogenetic potential in LGN initiation; however, other isotypes (IgA or IgE) as well as autoantibodies targeting other molecules (e.g. anti-C1q, anti-C reactive protein) can perpetuate renal injury. Conversely, protective autoantibodies are also likely in SLE which can contain renal damage targeting either DNA (i.e. IgM anti-DNA) or other molecules (e.g. pentraxin 3). Thus, lupus nephritogenic-antinephritogenic antibodies orchestrate the balance between harm and defence of renal tissue.
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Padova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Doria
authors.forename: M
authors.initials: M
authors.lastname: Gatto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D002843:Chromatin / Q000276:immunology; D004247:DNA / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation / Q000209:etiology / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008181:Lupus Nephritis / Q000276:immunology* / Q000503:physiopathology; D009707:Nucleosomes / Q000276:immunology
chemical_list: D001323:Autoantibodies; D002843:Chromatin; D007074:Immunoglobulin G; D009707:Nucleosomes; D004247:DNA