OP0117 MICRO-STRUCTURAL CHANGES ASSOCIATED WITH ANTI-CITRULLINATED VIMENTIN AUTOIMMUNITY IN RA-AT-RISK INDIVIDUALS PRECIPITATE THE ONSET OF RHEUMATOID ARTHRITIS
Authors: Arnd Kleyer, David Simon, Cong Duy Bui, Axel Hueber, Holger Bang, Andreas Ramming, Jürgen Rech, Gerhard Krönke, Georg Schett
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Development of rheumatoid arthritis (RA) is characterized by a several years lasting phase of autoimmunity, characterized by the presence of anti-modified protein antibodies (AMPA), recognizing citrullinated, carbamylated or acetylated proteins, as well as rheumatoid factor (RF) which precedes the onset of clinical disease (1,2).High resolution peripheral quantitative (HR-pQCT) technique enables the depiction of small cortical changes in peripheral joints (3). <h3>Objectives</h3> To describe microstructural bone lesions in rheumatoid arthritis (RA) at-risk individuals using HR-pQCT technique, their relation to rheumatoid arthritis specific autoimmunity, particularly osteoclast-inducing citrullinated vimentin (cVIM) antibodies and their impact on the later development of RA. <h3>Methods</h3> Cortical micro-channels (CoMiCs) as well as volumetric cortical and trabecular bone densities were analyzed by high-resolution computed tomography in the hand joints of RA at-risk individuals. Anti-modified protein antibody (AMPA) response was profiled including reactivities against citrullinated proteins (vimentin, enolase, fibrinogen) as well as carbamylated and acetylated vimentin. All subjects were followed for the development of RA. <h3>Results</h3> RA at-risk subjects (all N=75) with high-level (&gt;1000U) cVIM antibodies showed a broader AMPA response and significantly more severe microstructural changes (higher CoMiCs, lower cortical and trabecular bone volume) compared to subjects with low/no cVIM reactivity. High cVIM antibodies and microstructural changes (&gt;15 radial CoMiCs/joint) were associated with the presence of arthralgia. Furthermore, progression to RA was high in subjects with high cVIM (53%) vs. those with low (22%) or no (5%) antibodies and those with microstructural changes (46%) vs. those without such changes (16%). Conclusion: cVIM antibodies are associated to microstructural changes in RA at-risk individuals and predict the onset of RA. These data support the concept of structural priming of joints by autoimmunity before the onset of RA. <h3>References</h3> [1] McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365:2205-19. [2] Catrina AI, Svensson CI, Malmström V, Schett G, Klareskog L. Mechanisms leading from systemic autoimmunity to joint-specific disease in rheumatoid arthritis. Nat Rev Rheumatol. 2017;13:79-86. [3] Werner D, Simon D, Englbrecht M, et al. Early Changes of the Cortical Micro-Channel System in the Bare Area of the Joints of Patients With Rheumatoid Arthritis. Arthritis Rheumatol. 2017;69:1580-7. <h3>Disclosure of Interests</h3> Arnd Kleyer Grant/research support from: Lilly, Consultant for: Lilly, Speakers bureau: Abbvie, David Simon Grant/research support from: Novartis, Consultant for: Lilly, Speakers bureau: Janssen, Cong Duy Bui: None declared, Axel Hueber Grant/research support from: Novartis, Pfizer, Consultant for: Lilly, Speakers bureau: Lilly, Novartis, Janssen, Abbvie, Holger Bang Employee of: Dr. Bang is employee of the diagnostic company Orgentec Diagnostika., Andreas Ramming Grant/research support from: Novartis, Jürgen Rech Grant/research support from: Bristol-Myers Squibb and Celgene (greater than $10,000), Consultant for: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Speakers bureau: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Gerhard Krönke Grant/research support from: Lilly, Pfizer, Speakers bureau: Novartis, Georg Schett: None declared