Genetic factors for ACPA development in RA, especially human leukocyte antigen DR beta 1 (HLA-DRB1) shared epitope (SE) alleles, are thought to play a role in the epitope spreading and rise of ACPA levels after the initiation of ACPA production, which is HLA-DRB1 SE independent [35]. Here, PRTN3 is linked to rheumatoid arthritis.