TY - JOUR T1 - Antibodies and B cells recognising citrullinated proteins display a broad cross-reactivity towards other post-translational modifications JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 472 LP - 480 DO - 10.1136/annrheumdis-2019-216499 VL - 79 IS - 4 AU - T Kissel AU - S Reijm AU - LM Slot AU - M Cavallari AU - CM Wortel AU - RD Vergroesen AU - G Stoeken-Rijsbergen AU - JC Kwekkeboom AU - ASB Kampstra AU - EWN Levarht AU - JW Drijfhout AU - H Bang AU - KM Bonger AU - GMC Janssen AU - PA van Veelen AU - TWJ Huizinga AU - HU Scherer AU - M Reth AU - REM Toes Y1 - 2020/04/01 UR - http://ard.bmj.com/content/79/4/472.abstract N2 - 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. ER -