Detection of antibodies to deiminated recombinant rat filaggrin by enzyme‐linked immunosorbent assay: A highly effective test for the diagnosis of rheumatoid arthritis

Abstract

Objective. To assay antifilaggrin autoantibodies, we developed an enzyme-linked immunosorbent assay (ELISA) using a "citrullinated" recombinant rat filaggrin. Our objectives were to assess its value for diagnosing rheumatoid arthritis (RA) and to compare the results with those obtained using 4 other reference methods for detection of antifilaggrin autoantibodies, including the commercially available ELISA that uses a modified "citrullinated" synthetic peptide derived from the sequence of human filaggrin (CCP-ELISA).Methods. We analyzed 711 sera from patients with well-characterized rheumatic diseases, including 240 patients with RA. Antifilaggrin autoantibodies were detected by an ELISA using a recombinant rat filaggrin deiminated in vitro as immunosorbent (ArFA-ELISA). The results considered were the differences between the optical densities obtained on deiminated and nondeiminated proteins. Antibodies to rat esophagus epithelium were detected by indirect immunofluorescence, while antibodies to human filaggrin were detected by immunoblotting and by a recently described ELISA using a deiminated recombinant human filaggrin. Finally, CCP-ELISA was performed according to the manufacturer's recommendations.Results. At the titer thresholds allowing diagnostic specificities of 0.95, 0.985, and 0.99 to be reached, the diagnostic sensitivities of the ArFA-ELISA were 0.76, 0.67, and 0.65, respectively. At these 3 thresholds, the sensitivities were significantly higher than those of the 4 other tests. Despite incomplete overlapping of the 5 tests, the high diagnostic performance of the ArFA-ELISA allows us to propose this test to replace all the other methods for antifilaggrin autoantibody detection. Conclusion.ArFA-ELISA appears to be the most efficient test among those available for the detection of antifilaggrin autoantibodies, in terms of diagnostic accuracy for RA. Its diagnostic performance in early RA and its prognostic value are currently under evaluation.

Usefulness of anti -CCP antibodies in rheumatic diseases in Indian patients

“…Anti-CCP antibodies are highly speciÞ c (>90%) in the diagnosis of RA even though the sensitivity ranges from 33% to 87%. [8][9][10][11][12]18,19] The second-generation assays for detecting anti-CCP antibodies increased the sensitivity to 80% while retaining the specificity. [12] Anti-CCP antibodies are important for diagnosis in RA because they are as sensitive as and more specific than the IgM RFs in early and fully established diseases.…”

Relationship Between Rheumatoid Factor Isotypes and IgG Anti-Cyclic Citrullinated Peptide Antibodies

“…The Journal of on May 9, 2018 -Published by www.jrheum.org Downloaded from proteins, such as filaggrin 11 , vimentin 12 , and fibrinogen 13 , etc., have been shown to have high specificity and PPV for RA, far superior to that of RF IgM measured by turbidimetry. The most widely used IgG anti-cyclic citrullinated peptide assay is the second generation (CCP2) ELISA.…”

Clinical Significance of Anti-CCP Antibodies in Rheumatoid Arthritis

“…To date, a number of reports have demonstrated the clinical significance of autoantibodies to citrullinated filaggrin and CCP in the diagnosis of RA as summarized in Table 1 (3,5,6,(11)(12)(13)(14). Although the specificity of antifilaggrin/CCP antibodies in RA is more than 90% in almost all reports, the prevalence (sensitivity) of the same antibodies ranges from 33% to 87.2%.…”