Important new findings presented in this study include the following observations: There is a major heterogeneity among monoclonal ACPA generated from B cells from RA patients; We find that some, but not all, of these monoclonal ACPA show strong anti-nuclear binding patterns including binding to apoptotic cells; These anti-nuclear ACPA also react with activated neutrophils and NETs and the binding of these antibodies is largely independent on PAD-expression and is mediated by acetylation. This evidence concerns the gene PADI4 and rheumatoid arthritis.