Objective. To assess if microstructural bone lesions in individuals at risk of developing rheumatoid arthritis (RA) are related to the spectrum of anti-modified protein antibodies (AMPAs) and affect the risk of developing RA.Methods. Cortical microchannels as well as cortical and trabecular bone mineral density (BMD) volumes (expressed as mg hydroxyapatite/cm 3 ) were analyzed by high-resolution peripheral quantitative computed tomography of the hand joints of individuals at risk of RA. AMPA response was profiled, including reactivities against citrullinated proteins (vimentin, enolase, and fibrinogen) as well as carbamylated and acetylated vimentin. All subjects were followed up for the development of RA.Results. Subjects at risk of developing RA (n = 75) who had broad-spectrum AMPAs (6-8 reactivities) had significantly more severe microstructural changes, including a higher mean AE SD number of cortical microchannels per joint (95 AE 3) and lower total volumetric BMD (vBMD; 265 AE 45), trabecular vBMD (176 AE 42), and cortical vBMD (585 AE 138), than those with moderate AMPA reactivity (3-5 reactivities) (number of cortical microchannels, 79 AE 30; total vBMD, 293 AE 33; trabecular vBMD, 195 AE 32; and cortical vBMD, 627 AE 91) and those with narrow AMPA reactivity (1-2 reactivities) (number of cortical microchannels, 47 AE 20; total vBMD, 311 AE 34; trabecular vBMD, 211 AE 30; and cortical vBMD, 674 AE 56). Progressors to RA had significantly higher numbers of cortical microchannels (103 AE 30 versus 71 AE 35) and lower bone volume (258 AE 37 versus 295 AE 34) compared to nonprogressors. Furthermore, rate of progression to RA was high in subjects with broad AMPA reactivity (48%) versus those with medium AMPA reactivity (26%) or narrow AMPA reactivity (0%), as well as in those with a high number of cortical microchannels (44%) versus those with a low number of cortical microchannels (10%).Conclusion. Microstructural changes in individuals at risk of RA are associated with broad-spectrum autoimmunity and predict the onset of RA. These data support the concept of structural priming of joints by autoimmunity before the onset of the inflammatory phase of the disease.
BackgroundDevelopment 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).ObjectivesTo 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.MethodsCortical 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.ResultsRA at-risk subjects (all N=75) with high-level (>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 (>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.References[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.Disclosure of InterestsArnd 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 ...
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