Autoantibodies to deiminated fibrinogen are the most efficient serological criterion for the diagnosis of rheumatoid arthritis

Background

Antifilaggrin autoantibodies are recognized as the most specific serum marker in rheumatoid arthritis (RA). Their high diagnostic value led in the past few years to the development of several efficient tests for detection of these autoantibodies directed against deiminated ('citrullinated') peptidic epitopes borne by profilaggrin. We recently showed that deiminated forms of the α and β chains of fibrin are the major targets of antifilaggrin autoantibodies in the synovial tissue of RA patients. Consequently, we developed a new test to assay the serum autoantibodies to deiminated fibrinogen (AhFibA) and evaluated its diagnostic value in RA.

Methods

An enzyme-linked immunosorbent assay (ELISA) using in vitro deiminated human fibrinogen as immunosorbent was developed, and 617 sera from patients with well characterized rheumatic diseases, including 181 RA, were tested. The diagnostic performance of the AhFibA-ELISA was compared, in the same cohort of patients, to that of rheumatoid factor (RF) assayed by nephelometry, and to those of various methods for detection of antifilaggrin autoantibodies: indirect immunofluorescence ('antikeratin antibodies'), immunoblotting onto human epidermis filaggrin, CCP-ELISA and an ELISA on deiminated recombinant rat filaggrin (ArFA-ELISA).

Results

With a cut-off value allowing 95% of specificity to be reached, AhFibA were detected in 83% of the RA sera. At 98.5% specificity, 76% of the RA sera were positive. In contrast, at the same specificities, RF was detected in only 56% and 6% of the RA sera, respectively. In addition, the diagnostic performance of the AhFibA-ELISA was significantly higher than those of all the tests for antifilaggrin autoantibodies, including CCP-ELISA and ArFA-ELISA.

Conclusions

Presence of autoantibodies to deiminated human fibrinogen appears as the most efficient (specific and sensitive) serological criterion for the diagnosis of RA. Moreover, these results confirm that deiminated fibrin is a major B autoantigen in RA and sustain its probable involvement in the pathophysiology of the disease.