Furthermore, citrullinated proteins themselves can be pathogenic, as described for cFib.16, 17, 54 It will be interesting to see if ACPA for cTNC5 bind to cTNC found within the RA joint and trigger cytokine formation in the form of immune complexes, or whether citrullination of the FBG domain enhances its activation of TLR4.26 The citrullinated FBG peptide previously detected in RA synovial fluid31 comprised the sequence we found in cTNC1. This evidence concerns the gene TLR4 and rheumatoid arthritis.