J Korean Med Sci.  2005 Jun;20(3):473-478. 10.3346/jkms.2005.20.3.473.

Diagnostic Performances of Anti-Cyclic Citrullinated Peptides Antibody and Antifilaggrin Antibody in Korean Patients with Rheumatoid Arthritis

• Choi SW
• Lim MK
• Shin DH
• Park JJ
• Shim SC

• KMID: 1778509
• DOI: http://doi.org/10.3346/jkms.2005.20.3.473

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease of unknown etiology. We studied the diagnostic performances of anti-cyclic citrullinated peptides antibody (anti-CCP) assay and recombinant anti-citrullinated filaggrin antibody (AFA) assay by enzyme linked immunosorbent assay (ELISA) in patients with RA in Korea. Diagnostic performances of the anti-CCP assay and AFA assay were compared with that of rheumatoid factor (RF) latex fixation test. RF, anti-CCP, and AFA assays were performed in 324 RA patients, 251 control patients, and 286 healthy subjects. The optimal cut off values of each assay were determined at the maximal point of area under the curve by receiver-operator characteristics (ROC) curve. Sensitivity (72.8%) and specificity (92.0%) of anti-CCP were better than those of AFA (70.3%, 70.5%), respectively. The diagnostic performance of RF showed a sensitivity of 80.6% and a specificity of 78.5%. Anti-CCP and AFA showed positivity in 23.8% and 17.3% of seronegative RA patients, respectively. In conclusion, we consider that anti-CCP could be very useful serological assay for the diagnosis of RA, because anti-CCP revealed higher diagnostic specificity than RF and AFA at the optimal cut off values and could be performed by easy, convenient ELISA method.

Keyword

Arthritis, Rheumatoid; Rheumatoid Factor; Anti-cyclic citrullinated peptide; Anti-citrullinated filaggrin Antibody

MeSH Terms

Adolescent
Adult
Aged
Antibodies/*diagnostic use/immunology
Arthritis, Rheumatoid/*diagnosis/immunology
Comparative Study
Enzyme-Linked Immunosorbent Assay/methods
Female
Humans
Intermediate Filament Proteins/*immunology
Korea
Male
Middle Aged
Peptides, Cyclic/*immunology
Research Support, Non-U.S. Gov't
Rheumatoid Factor/immunology
Sensitivity and Specificity

Figure

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  Fig. 1 Receiver operator characteristics (ROC) curves of anti-CCP and RF with or without RA (p=0.857).

• 

  Fig. 2 Receiver operator characteristics (ROC) curves of AFA and RF with or without RA (p=0.000).

Reference

1. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988; 31:315–324. PMID: 3358796.

2. Schellekens GA, Visser H, de Jong BA, van den Hoogen FH, Hazes JM, Breedveld FC, van Venrooij WJ. The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum. 2000; 43:155–163. PMID: 10643712.

3. Kroot EJ, de Jong BA, van Leeuwen MA, Swinkels H, van den Hoogen FH, van't Hof M, van de Putte LB, van Rijswijk MH, van Venrooij WJ, van Riel PL. The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis. Arthritis Rheum. 2000; 43:1831–1835. PMID: 10943873.

4. Nienhuis RL, Mandema E. A new serum factor in patients with rheumatoid arthritis, the antiperinuclear factor. Ann Rheum Dis. 1964; 23:302–305. PMID: 14178016.

5. Simon M, Girbal E, Sebbag M, Gomes-Daudrix V, Vincent C, Salama G, Serre G. The cytokeratin filament-aggregating protein filaggrin in the target of the so-called "antikeratin antibodies", autoantibodies specific for rheumatoid arthritis. J Clin Invest. 1993; 92:1387–1393. PMID: 7690781.

6. Girbal E, Sebbag M, Gomes-Daudrix V, Simon M, Vincent C, Serre G. Characterization of the rat oesophagus epithelium antigens defined by the so-called "antikeratin antibodies", specific for rheumatoid arthritis. Ann Rheum Dis. 1993; 52:749–757. PMID: 7504913.

7. Serre G. Autoantibodies to filaggrin/deiminated fibrin (AFA) are useful for the diagnosis and prognosis of rheumatoid arthritis, and are probably involved in the pathophysiology of the disease. Joint Bone Spine. 2001; 68:103–105. PMID: 11324923.

8. Sebbag M, Simmon M, Vincent C, Masson-Bessiere C, Girbal E, Durieux JJ, Serre G. The antiperinuclear factor and the so-called "antikeratin antibodies" are the same rheumatoid arthritis-specific autoantibodies. J Clin Invest. 1995; 95:2672–2679. PMID: 7539459.

9. Vincent C, de Keyser F, Masson-Bessiere C, Sebbag M, Veys EM, Serre G. Antiperinuclear factor compared with the so called "antikeratin" antibodies and antibodies to human epidermis filaggrin, in the diagnosis of arthritides. Ann Rheum Dis. 1999; 58:42–48. PMID: 10343539.

10. Schellekens GA, de Jong BA, van den Hoogen FH, van de Putte LB, van Venrooij WJ. Citrulline is an essential constitute of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest. 1998; 101:273–281. PMID: 9421490.

11. Tarcsa E, Marekov LN, Mei G, Melino G, Lee SC, Steinert PM. Protein unfolding by peptidylarginine deiminase: substrate specificity and structural relationship of the natural substrates trichohyalin and filaggrin. J Biol Chem. 1996; 271:30709–30716. PMID: 8940048.

12. Nogueira L, Sebbag M, Vincent C, Arnaud M, Fournié B, Cantagrel A, Jolivet M, Serre G. Performance of two ELISAs for antifilaggrin autoantibodies, using either affinity purified or deiminated recombinant human filaggrin, in the diagnosis of rheumatoid arthritis. Ann Rheum Dis. 2001; 60:882–887. PMID: 11502616.

13. Visser H, Gelinck LB, Kampfraath AH, Breedveld FC, Hazes JM. Diagnostic and prognostic characteristics of the enzyme linked immunosorbent rheumatoid factor assays in rheumatoid arthritis. Ann Rheum Dis. 1996; 55:157–161. PMID: 8712877.

14. Emery P. The optimal management of early rheumatoid disease: the key to preventing disability. Br J Rheumatol. 1994; 33:765–768. PMID: 8055205.

15. Girbal-Neuhauser E, Durieux JJ, Arnaud M, Dalbon P, Sebbag M, Vincent C, Simon M, Senshu T, Masson-Bessière C, Joliver-Reynaud C. The epitopes targeted by the rheumatoid arthritis-associated anti-filaggrin autoantibodies are post-translationally generated on various sites of (pro) filaggrin by deimination of arginine residues. J Immunol. 1999; 162:585–594. PMID: 9886436.

16. Palosuo T, Lukka M, Alenius H, Kalkkinen N, Aho K, Kurki P, Heikkilä R, Nykänen M, von Essen R. Purification of filaggrin from human epidermis and measurement of antifilaggrin autoantibodies in sera from patients with rheumatoid arthritis by an enzyme-linked immunosorbent assay. Int Arch Allergy Immunol. 1998; 115:294–302. PMID: 9566352.

17. Aho K, Palosuo T, Lukka M, Kurki P, Isomaki H, Kautiainen H, von Essen R. Antifilaggrin antibodies in recent-onset arthritis. Scand J Rheumatol. 1999; 28:113–116. PMID: 10229141.

18. Harding CR, Scott IR. Histidine-rich proteins (filaggrins):structural and functional heterogeneity during epidermal differentiation. J Mol Biol. 1983; 170:651–673. PMID: 6195345.

19. Vittecoq O, Jouen-Beades F, Krzanowska K, Bichon-Tauvel I, Ménard JF, Daragon A, Tron F, Le Loët X. Rheumatoid factors, anti-filaggrin antibodies and low in vitro interleukin-2 and interferon-γ production are useful immunological markers for early diagnosis of community cases of rheumatoid arthritis. A preliminary study. Joint Bone Spine. 2001; 68:144–153. PMID: 11324930.