title: Autoantibodies in lupus: culprits or passive bystanders?
abstract: Several autoantibodies are culprits in the pathogenesis of organ damage in systemic lupus erythematosus, by means of established or postulated mechanisms, whereby inducing a perturbation of cell structure and function, with consequent tissue-organ impairment. Common autoantibody-mediated mechanisms of damage include cell surface binding with or without cytolysis, immune complex-mediated damage, penetration into living cells, binding to cross-reactive extracellular molecules. Experimental data from both murine models and humans have recently clarified the key role of autoantibodies in severe organ involvements, including nephritis, neuropsychiatric (NP) dysfunction, and cerebrovascular disease (CVD). In lupus nephritis early and late phases are distinguishable and mediated by different processes in which anti-chromatin antibodies are both inducing and perpetuating agents, by immune-complex formation and massive deposition in mesangial matrix at first, and in glomerular basement membrane at end-stage. Also NP abnormalities occur very early, much earlier than other systemic manifestations, and exacerbate with the increase in autoantibody titers. Among the autoantibodies mainly implicated in neurolupus, anti-β2 glycoprotein I (β2GPI) antibodies are preferentially involved in focal NP events which are a consequence of non-inflammatory microangiopathy; otherwise, anti-ribosomal P protein antibodies and N-methyl-d-aspartate receptor (NMDAR) antibodies cause diffuse NP events through a direct cytotoxic effect on neuronal cells at specific brain zones.
authors: Molecular Pathology Research Group, Institute of Medical Biology, University of Tromsø, Norway.
authors: Ole P
authors: OP
authors: Rekvig
authors: Chaim
authors: C
authors: Putterman
authors: Cinzia
authors: C
authors: Casu
authors: Hua-Xin
authors: HX
authors: Gao
authors: Anna
authors: A
authors: Ghirardello
authors: Elin S
authors: ES
authors: Mortensen
authors: Angela
authors: A
authors: Tincani
authors: Andrea
authors: A
authors: Doria
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D024201:Bystander Effect; D002843:Chromatin / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D050533:Glomerular Basement Membrane / Q000276:immunology*; D006801:Humans; D008181:Lupus Nephritis / Q000175:diagnosis / Q000276:immunology*; D020945:Lupus Vasculitis, Central Nervous System / Q000175:diagnosis / Q000276:immunology*; D026901:Membrane Transport Proteins / Q000276:immunology; D009474:Neurons / Q000276:immunology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D001324:Autoantigens; D002843:Chromatin; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; D016194:Receptors, N-Methyl-D-Aspartate