title: Autoantigens as Partners in Initiation and Propagation of Autoimmune Rheumatic Diseases.
abstract: Systemic autoimmune diseases are characterized by specific targeting of a limited group of ubiquitously expressed autoantigens by the immune system. This review examines the mechanisms underlying their selection as immune targets. Initiation of autoimmune responses likely reflects the presentation of antigens with a distinct structure not previously encountered by the immune system, in a proimmune context (injury, malignancy, or infection). Causes of modified structure include somatic mutation and posttranslational modifications (including citrullination and proteolysis). Many autoantigens are components of multimolecular complexes, and some of the other components may provide adjuvant activity. Propagation of autoimmune responses appears to reflect a bidirectional interaction between the immune response and the target tissues in a mutually reinforcing cycle: Immune effector pathways generate additional autoantigen, which feeds further immune response. We propose that this resonance may be a critical principle underlying disease propagation, with specific autoantigens functioning as the hubs around which amplification occurs.
authors.affiliation: Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224; email: arosen@jhmi.edu , lcr@jhmi.edu.
authors.forename: Antony
authors.initials: A
authors.lastname: Rosen
authors.affiliation: Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224; email: arosen@jhmi.edu , lcr@jhmi.edu.
authors.forename: Livia
authors.initials: L
authors.lastname: Casciola-Rosen
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity; D025461:Feedback, Physiological; D006801:Humans; D007108:Immune Tolerance; D016056:Immunodominant Epitopes / Q000276:immunology*; D046912:Multiprotein Complexes / Q000276:immunology*; D012216:Rheumatic Diseases / Q000276:immunology*; D013329:Structure-Activity Relationship
chemical_list: D000276:Adjuvants, Immunologic; D001324:Autoantigens; D016056:Immunodominant Epitopes; D046912:Multiprotein Complexes
keywords: autoantibodies; immunodominance; modified structure