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A comparative study of IgG second- and third-generation anti-cyclic citrullinated peptide (CCP) ELISAs and their combination with IgA third-generation CCP ELISA for the diagnosis of rheumatoid arthritis

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Abstract

To compare IgG anti-cyclic citrullinated peptide (CCP) enzyme-linked immunosorbent assays (ELISAs) of second (anti-CCP2) and third generations (anti-CCP3) for the diagnosis of rheumatoid arthritis (RA), an IgA CCP3 ELISA was also evaluated. Combinations of the use of the three tests were evaluated. Anti-CCP2 IgG, anti-CCP3 IgG, and anti-CCP3 IgA antibody levels were determined by ELISAs in the serum of 70 patients with rheumatoid arthritis, 34 patients with systemic lupus erythematosus (SLE), and 54 normal subjects. We evaluated the serum levels, diagnostic performance, and the use of a combination of tests for RA diagnosis. Statistical analyses include receiver operating curves (ROCs) and others. The serum levels were higher in RA patients. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio (LR), and negative LR were, respectively, 78.6%, 94.3%, 91.7%, 84.7%, 13.8, and 0.23 for anti- CCP2 IgG and 82.9%, 93.2%, 90.6%, 87.2%, 12.2, and 0.18 for anti-CCP3 IgG. These values were better than the same statistical tests for anti-CCP3 IgA. ROC analysis showed that anti-CCP2 IgG and anti-CCP3 IgG had good performance and similar areas. Measuring both IgG and IgA anti-CCP tests increases the specificity if both tests were positive and increases the sensitivity if either test were positive. In our population, anti-CCP2 IgG and anti-CCP3 IgG had good diagnostic performance. Anti-CCP3 IgG had 4.3% more sensitivity than the anti-CCP2 IgG test while sustaining high specificity. This and other studies suggest the development of a dual test—CCP3 IgG and IgA that may be a potential diagnostic tool.

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Acknowledgments

We are grateful to patients and healthy subjects who joined the study for contributed their valuable specimens and to the Hospital Universitario-Universidade Federal de Santa Catarina personnel for the special attention.

Disclosure

Lisiane M. E. Anjos: none; Ivanio A. Pereira: none; Eleonora d‘Orsi: none; and Edelton F. Morato: none. Andrea P. Seaman and Rufus W. Burlingame are employees of Inova Diagnostics, San Diego, CA, USA.

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Authors and Affiliations

  1. Universidade do Sul de Santa Catarina (UNISUL), Tubarao, Brazil

    Lisiane Maria Enriconi dos Anjos

  2. Universidade Federal de Santa Catarina (UFSC), Florianopolis, Brazil

    Ivanio Alves Pereira, Eleonora d ‘Orsi & Edelton Flavio Morato

  3. Inova Diagnostics, San Diego, CA, USA

    Andrea Piette Seaman & Rufus Watson Burlingame

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  1. Lisiane Maria Enriconi dos Anjos
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  6. Edelton Flavio Morato
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Correspondence to Edelton Flavio Morato.

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Enriconi dos Anjos, L.M., Pereira, I.A., d ‘Orsi, E. et al. A comparative study of IgG second- and third-generation anti-cyclic citrullinated peptide (CCP) ELISAs and their combination with IgA third-generation CCP ELISA for the diagnosis of rheumatoid arthritis. Clin Rheumatol 28, 153–158 (2009). https://doi.org/10.1007/s10067-008-0999-5

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