title: Lupus nephritis: role of antinucleosome autoantibodies.
abstract: The discovery of autoantigen clustering in blebs at the surface of apoptotic cells boosted research on the role of apoptosis in systemic lupus erythematosus (SLE) and led to the discovery of autoantigen modification during apoptosis. Normally, apoptotic cells are cleared efficiently and swiftly. However, it became clear that in SLE insufficient removal of apoptotic material leads to the release of these modified autoantigens. This creates the danger that these modified autoantigens are recognized by the immune system. Indeed, dendritic cells, the professional antigen-presenting cells, phagocytose these modified autoantigens, which leads to maturation and induction of a proinflammatory state of these dendritic cells. As a consequence, they present these modified autoantigens to T cells in an immunogenic way, which become activated and stimulate autoreactive B cells to secrete autoantibodies. In this review the currently available evidence for the sequential steps in the pathogenesis of SLE is discussed. Furthermore, the mechanisms responsible for the nephritogenicity of antinucleosome antibodies are reviewed. This will reveal that nucleosomes are not only a major driving force in the formation of antinuclear antibodies, but also play a pivotal role in the development of tissue lesions by mediating binding of autoantibodies to basement membranes as exemplified for the kidney.
authors.affiliation: Nephrology Research Laboratory, Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: van der Vlag
authors.forename: Jo H M
authors.initials: JH
authors.lastname: Berden
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D017209:Apoptosis; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008181:Lupus Nephritis / Q000209:etiology* / Q000276:immunology; D009707:Nucleosomes / Q000276:immunology*; D051193:Toll-Like Receptors / Q000502:physiology
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D016207:Cytokines; D009707:Nucleosomes; D051193:Toll-Like Receptors