Performance characteristics of three random access cyclic citrullinated peptide antibody assays

Abstract

Background: Cyclic citrullinated peptide antibodies (CCP Ab) are useful biomarkers for the early detection and diagnosis of rheumatoid arthritis (RA).

Methods: We evaluated the performance of 3 random access 2nd generation CCP Ab assays, the Abbott AxSYM and Architect analyzers and the Roche Modular Analytics E170 analyzer, for limit of detection (LOD), imprecision, results for samples from healthy subjects, analytic concordance, and interferences. Method comparison testing was performed using the AxSYM analyzer as the comparison method and a 3rd generation INOVA Quanta Lite ELISA assay was included.

Results: LOD determinations met the manufacturers' claims. Total CVs ranged from 1.6% to 8.2%. Results from healthy subjects were generally much lower than the manufacturers' decision cutoffs. Comparison to the AxSYM assay resulted in overall concordance ranging from 82.1% to 98.3%. These assays were resistant to interference from hemolysis, icterus, lipemia and rheumatoid factor.

Conclusion: All 3 random access CCP Ab assays performed according to the manufacturers' claims and have the potential to improve workflow in clinical laboratories.

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Evaluation of three automated enzyme immunoassays for detection of anti-cyclic citrullinated peptide antibodies in qualitative and quantitative aspects

Abstract

Objective. The anti-cyclic citrullinated peptide (anti-CCP) antibody has been increasingly used in the field of rheumatology, and various manufacturers have developed a variety of anti-CCP assays using mainly ELISA techniques. This study evaluated the performance of recently marketed automated chemiluminescence enzyme immunoassays for anti-CCP.

Methods. We investigated four anti-CCP assays (Diastat anti-CCP ELISA assay, Axsym anti-CCP assay on the Axsym system, the Architect anti-CCP assay on the Architect i2000 system and the Elecsys anti-CCP assay on the Cobas e 411 analyzer). Samples from 64 patients with RA and 152 controls, including patients with various autoimmune diseases, were studied. We assessed the clinical sensitivities and specificities, and compared the qualitative and quantitative results of each anti-CCP assay.

Results. Using the manufacturers' cut-off, diagnostic sensitivities ranged from 90.6 to 93.8% and the specificities ranged from 85.5 to 86.8%. The areas under the curve were comparable among the different assays, and qualitative agreements ranged from 97.2 to 99.1%. In the quantitative results, all anti-CCP assays were significantly correlated (P<0.001), but the correlation coefficient ranged from 0.615 to 0.861. Especially, the correlation coefficients between the automated anti-CCP assays were higher than those between the ELISA assay (Diastat) and the automated assays

Conclusions. The overall diagnostic performance of the automated anti-CCP assays was comparable, and it provides reliable information on antibody levels, making them useful in monitoring disease activity.

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Comparison of the second and third generation anti-cyclic citrullinated peptide antibody assays in the diagnosis of Japanese patients with rheumatoid arthritis

Abstract

The anti-cyclic citrullinated peptide (CCP) antibody has become increasingly important in the diagnosis of rheumatoid arthritis (RA), especially for early diagnosis. The purpose of this study is to compare the diagnostic usefulness of the second and third generation anti-CCP antibody kits among Japanese patients with RA. Anti-CCP antibody titers were measured with the second generation (MESACUP CCP test, Medical and biological laboratories) and third generation (QUANTA Lite CCP3 IgG ELISA, Inova Diagnostics) kits using serum samples from 106 rheumatoid arthritis (RA) patients and 57 non-RA patients. Sensitivities and specificities were compared. The sensitivity and specificity of the second generation anti- CCP (anti-CCP2) kit were 88.7 and 89.5%, and those of the third generation anti-CCP (anti-CCP3) kit were 91.5 and 87.7%. Area under the receiver operating curve showed that anti-CCP2 and anti-CCP3 had similar diagnostic performances. Diagnostic performance of the anti-CCP3 assay was comparable with the ant-CCP2 assay in Japanese patients with RA.

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Anti–Citrullinated Peptide Antibody Assays and Their Role in the Diagnosis of Rheumatoid Arthritis

The diagnosis of early rheumatoid arthritis (RA) has relied on clinical criteria, including history and physical examination findings and laboratory and radiographic results. Irreversible damage frequently occurs early in RA (1-5). With mounting evidence supporting early diagnosis and aggressive treatment to prevent damage and disability, there is a need to improve identification and diagnosis of early RA (6). Until recently, assays detecting rheumatoid factor (RF), antibodies directed against the Fc portion of the IgG molecule, have been the primary serologic tests for RA diagnosis. Anti-citrullinated peptide antibody (ACPA) assays, developed and commercialized in the past decade, are now being employed clinically. Since ACPAs are present before the onset of RA symptoms and are predictive of RA development, they are a valuable diagnostic test early in the course of the disease (4).

This review synthesizes currently available data regarding the diagnostic properties of RF and ACPAs for the diagnosis of early RA. We focus on ACPAs, given their recent development and their potential role in the improved identification of early, undifferentiated RA. Data included in this review were obtained from medical literature searches, Web sites of and contact with companies marketing the assays, and information and opinions obtained from experts in the field. We have included information on the biologic basis and development of ACPA assays, the available assays, and data concerning assay performance characteristics, in particular those published in peer-reviewed journals, but also those publicized by manufacturers. Diagnostic properties of these tests are reviewed, including but not limited to sensitivity, specificity, and positive and negative predictive values.

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