Arginine residues in the terminal clotting factor fibrinogen, which is present in high concentrations in blood, can be converted to citrulline residues by peptidylarginine deiminase 4 (PAD4). Antibodies capable of recognizing citrullinated proteins, including citrulliunated fibrinogen, are found in the majority of patients with rheumatoid arthritis (RA). Immunization of mice with PAD4-citrullinated human fibrinogen has been reported to induce an arthritis that resembles human RA .
Zhao, X., Okeke, N.L., Sharpe, O., et al. Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis. Arthritis Research & Therapy 10(4), (2008).
Saraiva AL, Peres RS, Veras FP, Talbot J, de Lima KA, Luiz JPM, Cunha TM, Louzada-Junior P, Cunha FQ, Alves-Filho JC. Citrullinated human fibrinogen triggers arthritis through an inflammatory response mediated by IL-23/IL-17 immune axis. Int Immunopharmacol. 2021 Dec;101(Pt B):108363. doi: 10.1016/j.intimp.2021.108363. Epub 2021 Nov 19.
Hill, J.A., Al-Bishri, J., Gladman, D.D., et al. Serum autoantibodies that bind citrullinated fibrinogen are frequently found in patients with rheumatoid arthritis. Journal of Rheumatology 33(11), 2115-2119(2006).
Jonathan A. Hill, David A. Bell, William Brintnell, David Yue, Bret Wehrli, Anthony M. Jevnikar, David M. Lee, Wolfgang Hueber, William H. Robinson, Ewa Cairns; Arthritis induced by posttranslationally modified (citrullinated) fibrinogen in DR4-IE transgenic mice . J Exp Med 14 April 2008; 205 (4): 967–979. doi: https://doi.org/10.1084/jem.20072051