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42. Kongress der Deutschen Gesellschaft für Rheumatologie, 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie, 24. Wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie

17.-20. September 2014, Düsseldorf

Autoantibodies to citrullinated type II collagen directly bind to cartilage of patients with rheumatoid arthritis

Meeting Abstract

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  • Nadine Schneider - Klinikum der Johann Wolfgang Goethe-Universität, Medizinische Klinik II, Rheumatologie, Frankfurt/Main
  • Sabrina Haag - Karolinska Institute, Stockholm, Schweden

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 42. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 24. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Düsseldorf, 17.-20.09.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. DocER.03

doi: 10.3205/14dgrh070, urn:nbn:de:0183-14dgrh0702

Published: September 12, 2014

© 2014 Schneider et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

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Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease which is characterised by the presence of autoantibodies, such as rheumatoid factors and anti-citrullinated protein antibodies (ACPA), which are valuable biomarkers that can be detected even before clinical onset. Citrullination is catalyzed by a family of calcium dependent enzymes, called peptidylarginine deiminases (PADs), of which two isotypes, PAD2 and PAD4, are predominantly expressed in the inflamed synovium. To date the direct functional role of ACPAs in the induction of joint inflammation has not yet been clarified despite a mountain of indirect evidence for a significant contribution of citrullination to the pathogenesis of RA. The aim of the study was to indentify potential citrullinated neoepitopes of type II collagen (CII) in sera of RA patients as well as the detection of these epitopes in cartilage tissue in situ.

Methods: The identification of potential citrullinated neoepitopes was performed by high-resolution tandem mass spectrometry (MS) of in vitro PAD2 treated CII. Based on the MS analyses, synthetic peptides were designed and analyzed using ELISA for serum IgG reactivity in 356 RA patients. Affinity-purified antibodies from RA sera directed to citrullinated CII were used for immunohistochemistry.

Results: CII contains 52 arginines in its triple helical region, of which 30 were identified as being citrullinated, and six of those being only detected after PAD-treatment at 37°C. Seven of the identified citrullinated arginines are part of previously described antibody epitopes on CII (e.g. R927 and R933 on the F4 epitope). Affinity-purified antibodies directed against the citrullinated F4 epitope on CII stained RA cartilage both in the interterritorial and also pericellular extracellular matrix.

Conclusion: These experiments show for the first time that human ACPAs bind to cartilage from RA patients, suggesting a contribution of cartilage-directed anti-citrulline immunity to the induction of joint inflammation in RA.