Diagnostic value of anti-human citrullinated fibrinogen ELISA and comparison with four other anti-citrullinated protein assays

Abstract

We studied the diagnostic performance of the anti-human citrullinated fibrinogen antibody (AhFibA) ELISA for rheumatoid arthritis (RA) in a consecutive cohort (population 1) and evaluated the agreement between the AhFibA ELISA and four other assays for anti-citrullinated protein/peptide antibodies (ACPAs) as well as rheumatoid factor in patients with longstanding RA (population 2). Population 1 consisted of 1024 patients with rheumatic symptoms; serum samples from these patients were sent to our laboratory for ACPA testing within the context of a diagnostic investigation for RA. Ninety-two of these patients were classified as having RA according to the American College of Rheumatology criteria and 463 were classified as non-RA patients. Population 2 consisted of 180 patients with longstanding RA and was used to assess agreement and correlations between five ACPA assays: anti-cyclic citrullinated peptide (CCP)1 and anti-CCP2 antibodies were detected using a commercially available ELISA, AhFibA using ELISA, and anti-PepA and anti-PepB antibodies using line immunoassay. Applying previously proposed cut-offs for AhFibA, we obtained a sensitivity of 60.9% and a specificity of 98.7% in population 1. Receiver operating characteristic curve analysis could not detect a significant difference in diagnostic performance between the AhFibA ELISA and anti-CCP2 assay. Performing a hierarchical nearest neighborhood cluster analysis of the five different ACPA assays in population 2, we identified two clusters: a cluster of anti-pepA, anti-pepB and anti-CCP1, and a cluster of AhFibA and anti-CCP2. In conclusion, we found that AhFibA and anti-CCP2 antibodies had similar diagnostic performance. However, disagreement between ACPA tests may occur.

Figure 1

ROC curve analyses of the RF, AhFibA and anti-CCP2 assay in population 1. (a) The whole curve is shown, and (b) with a focus on detail of the ROC curve at the 98% specificity level for the AhFibA and anti-CCP2 assay in population 1. AhFibA, anti-human fibrinogen (auto)antibodies; CCP, cyclic citrullinated peptide; RF, rheumatoid factor; ROC, receiver operating curve.

Figure 2

Scatter plot: AhFibA assay versus anti-CCP2 assay in population 1. Ab, antibody; AhFibA = anti-human fibrinogen (auto)antibodies; CCP = cyclic citrullinated peptide.

Figure 3

Dendrogram of the cluster analysis of the different ACPA assays in population 2. ACPA, anti-citrullinated protein/peptide antibody; AhFibA, anti-human fibrinogen (auto)antibodies; CCP, cyclic citrullinated peptide; RF, rheumatoid factor.