title: Emerging and critical issues in the pathogenesis of lupus.
abstract: Systemic lupus erythematosus (SLE) is a multisystemic, autoimmune disease, encompassing either mild or severe manifestations. SLE was originally labeled as being an immune complex-mediated disease, but further knowledge suggested its pathogenesis is motlier than that, involving complex interactions between predisposed individuals and their environment. People affected with SLE have their immune system skewed toward aberrant self-recognition usually after encountering a triggering agent. Defeats in early and late immune checkpoints contribute to tolerance breakdown and further generation and expansion of autoreactive cell-clones. B and T cells play a master role in SLE, however clues are emerging about other cell types and new light is being shed on SLE autoantibodies, since some of them display really harmful potential (pathogenic antibodies), while others are just connected with disease development (pathological antibodies) and may even be protective. Autoantibody generation is elicited by abnormal apoptosis and inefficient clearance of cellular debris causing intracellular autoantigens (e.g. nucleosomes) to persist in the extracellular environment, being further recognized by autoreactive cells. Here we explore the complexity of SLE pathogenesis through five core issues, i.e. genetic predisposition, B and T cell abnormalities, abnormal autoantigen availability, autoantibody generation and organ damage, relying on current knowledge and recent insights into SLE development.
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
authors.forename: Mariele
authors.initials: M
authors.lastname: Gatto
authors.forename: Margherita
authors.initials: M
authors.lastname: Zen
authors.forename: Anna
authors.initials: A
authors.lastname: Ghirardello
authors.forename: Silvano
authors.initials: S
authors.lastname: Bettio
authors.forename: Nicola
authors.initials: N
authors.lastname: Bassi
authors.forename: Luca
authors.initials: L
authors.lastname: Iaccarino
authors.forename: Leonardo
authors.initials: L
authors.lastname: Punzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Doria
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D044127:Epigenesis, Genetic; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D001323:Autoantibodies