Antibodies against citrullinated proteins enhance tissue injury in experimental autoimmune arthritis
Kristine A. Kuhn,Liudmila Kulik,Beren H. Tomooka,Kristin J. Braschler,William P. Arend,William H. Robinson,V. Michael Holers +6 more
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TLDR
It is demonstrated that antibodies against citrullinated proteins are centrally involved in the pathogenesis of autoimmune arthritis.Abstract:
Antibodies against citrullinated proteins are specific and predictive markers for rheumatoid arthritis although the pathologic relevance of these antibodies remains unclear. To investigate the significance of these autoantibodies, collagen-induced arthritis (CIA) in mice was used to establish an animal model of antibody reactivity to citrullinated proteins. DBA/1J mice were immunized with bovine type II collagen (CII) at days 0 and 21, and serum was collected every 7 days for analysis. Antibodies against both CII and cyclic citrullinated peptide, one such citrullinated antigen, appeared early after immunization, before joint swelling was observed. Further, these antibodies demonstrated specific binding to citrullinated filaggrin in rat esophagus by indirect immunofluorescence and citrullinated fibrinogen by Western blot. To evaluate the role of immune responses to citrullinated proteins in CIA, mice were tolerized with a citrulline-containing peptide, followed by antigen challenge with CII. Tolerized mice demonstrated significantly reduced disease severity and incidence compared with controls. We also identified novel murine monoclonal antibodies specific to citrullinated fibrinogen that enhanced arthritis when coadministered with a submaximal dose of anti-CII antibodies and bound targets within the inflamed synovium of mice with CIA. These results demonstrate that antibodies against citrullinated proteins are centrally involved in the pathogenesis of autoimmune arthritis.read more
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Fibrinogen as a key regulator of inflammation in disease
TL;DR: The role of fibrinogen in inflammatory disease is focused on highlighting its unique structural properties, cellular targets, and signal transduction pathways that make it a potent proinflammatory mediator and a potential therapeutic target.
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Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin
Ulrike Harre,Dan Georgess,Holger Bang,Aline Bozec,Roland Axmann,Elena Ossipova,Per-Johan Jakobsson,Wolfgang Baum,Falk Nimmerjahn,Eszter Szarka,Gabriella Sármay,G Krumbholz,Elena Neumann,René E. M. Toes,Hans Scherer,Anca I. Catrina,Lars Klareskog,Pierre Jurdic,Georg Schett +18 more
TL;DR: It is suggested that autoantibody formation in response to citrullinated vimentin directly induces bone loss, providing a link between the adaptive immune system and bone.
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Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage
Jing Shi,Rachel Knevel,Parawee Suwannalai,Michael P M van der Linden,George M.C. Janssen,Peter A. van Veelen,Nivine E. W. Levarht,Annette H M van der Helm-van Mil,Anthony Cerami,Tom W J Huizinga,René E. M. Toes,Leendert A. Trouw +11 more
TL;DR: Data show the presence of a unique autoantibody system recognizing carbamylated, but not citrullinated, protein antigens in the sera of rheumatoid arthritis patients, indicating that anti-CarP antibodies are a unique and relevant serological marker for ACPA-negative RA.
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Immunity to Citrullinated Proteins in Rheumatoid Arthritis
TL;DR: A new etiological model is proposed for ACPA-positive RA, built on MHC class II-dependent activation of adaptive immunity, which provides a new basis for molecular studies on the pathogenesis of AC PA-positive arthritis.
Journal ArticleDOI
Ectopic Lymphoid Structures Support Ongoing Production of Class-Switched Autoantibodies in Rheumatoid Synovium
Frances Humby,Michele Bombardieri,Antonio Manzo,Stephen Kelly,Mark Blades,Bruce Kirkham,Jo Spencer,Costantino Pitzalis +7 more
TL;DR: It is demonstrated that FDC+ follicular units invariably express AID and are surrounded by ACPA-producing plasma cells, providing strong evidence that ectopic lymphoid structures in the RA synovium are functional and support autoantibody production.
References
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Journal Article
Revised criteria for the classification of rheumatoid arthritis.
TL;DR: The Bulletin on the Rheumatic Diseases has published all of the classification criteria for the rheumatic diseases to date, and these new revised classified criteria for rheumatoid arthritis are very important as they should provide understanding of the possibly changing face of rheumatism.
Journal ArticleDOI
Revised criteria for the classification of rheumatoid arthritis.
TL;DR: The Bulletin on the Rheumatic Diseases has published all of the classification criteria for rheumatic diseases to date as mentioned in this paper, and these new revised classification criteria are very important as they should provide understanding of the possibly changing face of rheumatoid arthritis.
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