Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 39, Pages 16758-16763Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0909132106
Keywords
autoimmunity; complement; Fc receptor; rheumatic; lupus
Categories
Funding
- National Institutes of Health [R01 AR046580, K08 AR054317]
- Joslin's National Institute of Diabetes and Digestive and Kidney Diseases
- Diabetes and Endocrinology Research Center
- Pfizer Postdoctoral Fellowship
- Arthritis Foundation Arthritis Investigator Award
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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 FcR gamma-using receptors; conversely, endocarditis depended essentially on FcR gamma 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.
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