Academic Journal
Antibodies and B cells recognising citrullinated proteins display a broad cross-reactivity towards other post-translational modifications
| العنوان: | Antibodies and B cells recognising citrullinated proteins display a broad cross-reactivity towards other post-translational modifications |
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| المؤلفون: | Kissel, T, Reijm, S, Slot, LM, Cavallari, M, Wortel, CM, Vergroesen, RD, Stoeken-Rijsbergen, G, Kwekkeboom, JC, Kampstra, ASB, Levarht, EWN, Drijfhout, JW, Bang, H, Bonger, KM, Janssen, GMC, van Veelen, PA, Huizinga, TWJ, Scherer, HU, Reth, M, Toes, REM |
| بيانات النشر: | BMJ Publishing Group Ltd |
| سنة النشر: | 2020 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | Rheumatoid arthritis |
| الوصف: | Objective Autoantibodies against antigens carrying distinct post-translational modifications (PTMs), such as citrulline, homocitrulline or acetyllysine, are hallmarks of rheumatoid arthritis (RA). The relation between these anti-modified protein antibody (AMPA)-classes is poorly understood as is the ability of different PTM-antigens to activate B-cell receptors (BCRs) directed against citrullinated proteins (CP). Insights into the nature of PTMs able to activate such B cells are pivotal to understand the ‘evolution’ of the autoimmune response conceivable underlying the disease. Here, we investigated the cross-reactivity of monoclonal AMPA and the ability of different types of PTM-antigens to activate CP-reactive BCRs. Methods BCR sequences from B cells isolated using citrullinated or acetylated antigens were used to produce monoclonal antibodies (mAb) followed by a detailed analysis of their cross-reactivity towards PTM-antigens. Ramos B-cell transfectants expressing CP-reactive IgG BCRs were generated and their activation on stimulation with PTM-antigens investigated. Results Most mAbs were highly cross-reactive towards multiple PTMs, while no reactivity was observed to the unmodified controls. B cells carrying CP-reactive BCRs showed activation on stimulation with various types of PTM-antigens. Conclusions Our study illustrates that AMPA exhibit a high cross-reactivity towards at least two PTMs indicating that their recognition pattern is not confined to one type of modification. Furthermore, our data show that CP-reactive B cells are not only activated by citrullinated, but also by carbamylated and/or acetylated antigens. These data are vital for the understanding of the breach of B-cell tolerance against PTM-antigens and the possible contribution of these antigens to RA-pathogenesis. |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| Relation: | http://ard.bmj.com/cgi/content/short/79/4/472; http://dx.doi.org/10.1136/annrheumdis-2019-216499 |
| DOI: | 10.1136/annrheumdis-2019-216499 |
| الاتاحة: | http://ard.bmj.com/cgi/content/short/79/4/472 https://doi.org/10.1136/annrheumdis-2019-216499 |
| Rights: | Copyright (C) 2020, BMJ Publishing Group Ltd |
| رقم الانضمام: | edsbas.2016E067 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1136/annrheumdis-2019-216499 |
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