PADI4 and rheumatoid arthritis: In addition, it has been demonstrated that ACPAs in the peripheral blood and synovial fluid of RA patients support neutrophil extracellular trap (NET) formation [129] and release of PAD enzymes [130], which increases the milieu of citrullinated antigens that could drive the generation of new high-affinity ACPAs and/or amplify ACPA production in the synovium [131], thus forming a vicious cycle in RA development.