Fibrinogen structure is a large complex protein — a 340 kDa hexameric homodimer — that has complex roles in hemostasis and homeostasis. Synthesis of fibrinogen is constitutively expressed in the liver and synthesis upregulated at the transcriptional and translational levels in response to inflammation. During coagulation, thrombin-mediated proteolytic cleavage of fibrinogen yields protofibrils that mature into mechanical stabile fibrin clots. The interaction of fibrinogen with plasma proteins and with receptors on many cell types play roles in multiple physiological and pathological processes, including hemostasis, thrombosis, pregnancy, inflammation, infection, and cancer. Disorders in fibrinogen concentration and/or function increase risk of bleeding, thrombosis, and infection.
Arginine residues in fibrinogen and other proteins can be converted to citrulline residues by peptidylarginine deiminases. 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 .
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