Kissel T, Reijm S, Slot LM, et al. - In this study, the cross-reactivity of monoclonal AMPA and the ability of different types of post-translational modification (PTM)-antigens to activate citrullinated proteins (CP)-reactive B-cell receptors (BCRs) were examined. BCR sequences from B cells isolated utilizing citrullinated or acetylated antigens were applied to deliver monoclonal antibodies (mAb) followed by a detailed analysis of their cross-reactivity towards PTM-antigens. While no reactivity was noted to the unmodified controls, most mAbs were highly cross-reactive towards multiple PTMs. Evidence showed that B cells carrying CP-reactive BCRs confirmed activation on stimulation with various types of PTM-antigens. This research demonstrates that AMPA exhibit a high cross-reactivity towards at least two PTMs showing that their recognition pattern is not limited to one type of modification. Moreover, the evidence display that CP-reactive B cells are not only activated by citrullinated, but also by carbamylated and/or acetylated antigens. These findings are essential for the belief of the breach of B-cell tolerance against PTM-antigens and the feasible contribution of these antigens to RA-pathogenesis.