title: The same systemic autoimmune disease provokes arthritis and endocarditis via distinct mechanisms.
abstract: The immune mechanisms that provoke concomitant inflammation of synovial joints and cardiac valves in disorders such as rheumatic fever and systemic lupus erythematosus remain poorly defined. Here, we report the discovery of spontaneous endocarditis-in addition to their well-studied autoimmune arthritis-in K/BxN T cell receptor (TCR) transgenic mice. The same adaptive immune system elements were required for initiation of arthritis and endocarditis, and both diseases were dependent on autoantibodies. In contrast, the participation of key innate immune system molecules and perhaps T cells as effectors of inflammation differed between the 2 target tissues. Arthritis in K/BxN TCR transgenic mice depended primarily on complement C5 and not FcRgamma-using receptors; conversely, endocarditis depended essentially on FcRgamma receptors and not C5. Elucidating how a single systemic autoimmune disease engages distinct immune effector pathways to damage different target tissues is essential for optimizing the treatment of such disorders.
authors.affiliation: Section on Immunology and Immunogenetics, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA. binstadt@umn.edu
authors.forename: Bryce A
authors.initials: BA
authors.lastname: Binstadt
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hebert
authors.forename: Adriana
authors.initials: A
authors.lastname: Ortiz-Lopez
authors.forename: Roderick
authors.initials: R
authors.lastname: Bronson
authors.forename: Christophe
authors.initials: C
authors.lastname: Benoist
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
mesh_terms: D000818:Animals; D001168:Arthritis / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D004195:Disease Models, Animal; D004696:Endocarditis / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D001323:Autoantibodies