Likewise, the detection of ACPA in the synovial fluid of patients with RA [33,34], the demonstration that ACPA are concentrated at this site [35], and the detection of ACPA in the sera of SCID mice xenotransplanted with human synovium [36], support the possibility that ACPA might be directly generated in the synovium. This evidence concerns the gene PRTN3 and rheumatoid arthritis.