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A comparison of the frequency of antibodies to cyclic citrullinated peptides using a third generation anti-CCP assay (CCP3) in systemic sclerosis, primary biliary cirrhosis and rheumatoid arthritis

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Abstract

The objective was to investigate the frequency of anti-cyclic citrullinated peptides (CCP) antibodies in systemic sclerosis (SSc) and primary biliary cirrhosis (PBC), utilizing a new “third generation” anti-CCP ELISA (anti-CCP3) kit and a conventional anti-CCP2 assay. Patients with PBC, SSc, RA, and normal controls were included in the study. Serum samples were screened for autoantibodies by indirect immunofluorescence (IIF), antibodies to CCP by a second- and third-generation ELISA, antibodies to “scleroderma” antigens (CENP B, Scl-70, PM/Scl and fibrillarin—Scl-34) by a line immunoassay (LIA), and IgM RF by ELISA. The frequency of anti-CCP2 antibodies in SSc and PBC samples was 14.8% (11/74) and 6.2% (5/80), respectively, and the frequency of anti-CCP3 antibodies in SSc was 13.5% (10/74) and in PBC was 3.7% (3/80). By comparison, in the RA group the frequency of anti-CCP3 and anti-CCP2 antibodies was 79.1% (38/48) and 77% (37/48), respectively. Anti-CCP3 ELISA had a sensitivity, specificity, and positive and negative likelihood ratios (LR) of 79% (95% confidence interval [CI] = 64–89%), 93% (95% CI = 88–96%), 11.8 (95% CI = 6.8–20.3), and 0.22 (95% CI = 0.12–0.38), respectively. By comparison, the anti-CCP2 assay had a sensitivity, specificity, and positive and negative LRs of 77% (95% CI = 62–87), 90% (95% CI = 85–94), 8.3 (95% CI = 5.2–13.2), and 0.25 (95% CI = 0.15–0.42), respectively. In patients with SSc, there was an association of anti-CCP2 antibodies with the presence of arthritis, but there was no association of anti-CCP2 or anti-CCP3 with anti-CENP B, anti-Scl 70, or RF. This study confirmed the high specificity and sensitivity of both anti-CCP assays for the diagnosis of RA. The presence of anti-CCP antibodies in SSc was only correlated with the presence of arthritis.

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Abbreviations

ALBIA:

Addressable laser bead immunoassay

CCP:

Cyclic citrullinated peptide

ELISA:

Enzyme linked immunoassay

PBC:

Primary biliary cirrhosis

RA:

Rheumatiod arthritis

SPSS:

Statistical package for the Social Sciences

SSc:

Systemic sclerosis

SSN:

Serum sample number

U:

Units

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Acknowledgments

The authors acknowledge the technical assistance of Jane Zhang and Mark Fritzler. This study was supported by grants #38034 and #10884 from the Canadian Institutes of Health Research. MJF holds the Arthritis Society Research Chair at the University of Calgary, and funds from this endowment supported the sabbatical leave of MS. MS also received a scholarship from CAPES—Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Diagnostic kits for CCP3, gp210, and rheumatoid factor were generous gifts of INOVA Diagnostics, San Diego, CA. HEp-2 kits were a gift of ImmunoConcepts Inc., Sacramento, CA.

Conflict of Interest Statement

Mittermayer Santiago: none

Murray Baron: none

Kiyomitsu Miyachi: none

Canadian Scleroderma Research Group: none

Marvin Fritzler: is a paid consultant of ImmunoConcepts Inc. (Sacramento, CA)

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Authors and Affiliations

  1. Servico de Reumatologia do Hospital do Santa Izabel, Escola Bahiana de Medicina e Saude Publica, Salvador, Brazil

    Mittermayer Santiago

  2. Division of Rheumatology, Jewish General Hospital, McGill University, Montréal, PQ, Canada

    Murray Baron

  3. First Diagnostic Division, Health Sciences Research Institute, Yokohama, Japan

    Kiyomitsu Miyachi

  4. Faculty of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB, T2N 4N1, Canada

    Marvin J. Fritzler

  5. Canadian Scleroderma Research Group, Calgary, AB, Canada

    M. Abu-Hakima & S. Leclercq

  6. Canadian Scleroderma Research Group, Toronto, ON, Canada

    M. Bell

  7. Canadian Scleroderma Research Group, Montreal, PQ, Canada

    M. Hudson, J-P. Mathieu & S. Taillefer

  8. Canadian Scleroderma Research Group, Edmonton, AB, Canada

    N. Jones

  9. Canadian Scleroderma Research Group, Moncton, NB, Canada

    P. Docherty

  10. Canadian Scleroderma Research Group, St John’s, NL, Canada

    M. Khraishi

  11. Canadian Scleroderma Research Group, Saskatoon, SK, Canada

    J. Markland

  12. Canadian Scleroderma Research Group, London, ON, Canada

    J. Pope

  13. Canadian Scleroderma Research Group, Winnipeg, MB, Canada

    D. Robinson

  14. Canadian Scleroderma Research Group, Ottawa, ON, Canada

    D. Smith

  15. Canadian Scleroderma Research Group, Halifax, NS, Canada

    E. Sutton

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  1. Mittermayer Santiago
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  2. Murray Baron
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  15. J. Pope
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  16. D. Robinson
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  18. E. Sutton
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Corresponding author

Correspondence to Marvin J. Fritzler.

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Santiago, M., Baron, M., Miyachi, K. et al. A comparison of the frequency of antibodies to cyclic citrullinated peptides using a third generation anti-CCP assay (CCP3) in systemic sclerosis, primary biliary cirrhosis and rheumatoid arthritis. Clin Rheumatol 27, 77–83 (2008). https://doi.org/10.1007/s10067-007-0656-4

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  • DOI: https://doi.org/10.1007/s10067-007-0656-4

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