Serum autoantibodies that bind citrullinated fibrinogen are frequently found in patients with rheumatoid arthritis

Objective. Autoantibodies that bind citrullinated antigens are a sensitive and specific marker for rheumatoid arthritis (RA). While synthetic cyclic citrullinated peptides (CCP) are typically used to identity these antibodies, little is known about antibody reactivity to the predominant citrullinated protein found in the inflamed synovium, citrullinated fibrinogen (CitFib). We assessed the prevalence of anti-CitFib antibodies in patients with various rheumatic diseases. Methods. In total, 65 patients with established RA and 63 patients with other rheumatic diseases were tested for serum IgM rheumatoid factor (RF), IgG anti-CCP2, and IgG anti-CitFib antibodies. This cohort was used to determine optimal positive cutoff values for antibody reactivity to CitFib through receiver operating characteristic curve analysis. The specificity of these assays was confirmed with sera from 49 patients with psoriatic arthritis. Results. Antibodies to both citrullinated antigens were identified in the majority of RA patients tested. The overall sensitivity and specificity of the assays were: CCP 82%, 96%, CitFib 75%, 98%, and IgM RF 80%, 64%, respectively. All but one patient that was positive for CitFib was also positive for CCP2, and close to half the RF-negative RA patients were positive for CitFib and CCP2. Conclusion. These results suggest that autoimmunity to CitFib is common in patients with RA and may play a role in disease pathogenesis