抗原
瓜氨酸化
抗体
表位
单克隆抗体
自身抗体
B细胞
免疫学
化学
生物
细胞生物学
瓜氨酸
生物化学
氨基酸
精氨酸
作者
Theresa Kissel,Sanne Reijm,Linda M. Slot,Marco Cavallari,C. Wortel,Rochelle D Vergroesen,Gerrie Stoeken-Rijsbergen,Joanneke C Kwekkeboom,Arieke S. B. Kampstra,E. W. Nivine Levarht,Jan W. Drijfhout,Holger Bang,Kimberly M. Bonger,George M.C. Janssen,Peter A. van Veelen,Tom W J Huizinga,Hans Ulrich Scherer,Michael Reth,René Toes
标识
DOI:10.1136/annrheumdis-2019-216499
摘要
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.
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