Issues‎ > ‎vol2n1‎ > ‎

jsmc-10022


DIAGNOSTIC VALUE OF ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODIES IN RHEUMATOID ARTHRITIS; COMPARED WITH IGM AND IGA RHEUMATOID FACTORS


Dana Mohammed Tofiq*, Khalida M. Mousawy ** and Raouf Rahim Mirza ***



*   Department of Microbiology, School of Medicine, Faculty of Medical Sciences, University of Sulaimani.
**  Department of Microbiology, College of Medicine, University of Baghdad.
*** Department of Medicine, School of Medicine, Faculty of Medical Sciences, University of Sulaimani.


Submitted: 5/2/2012; Accepted: 15/4/2012Published 1/12/2012


ABSTRACT


Background  

As modern treatment of rheumatoid arthritis is shifting toward aggressive anti-rheumatic therapy in an early phase of the disease to prevent the progression of joint damage (which is irreversible), diagnostic tests with high specificity are desirable.

Objective

To compare the diagnostic value (sensitivity and specificity) of the three tests (anti-cyclic citrullinated peptide antibodies, rheumatoid factors IgM and IgA) in rheumatoid arthritis; to determine the test which gives the best combination of diagnostic sensitivity and specificity.

Patients and Methods

There were 47 rheumatoid patients, 16 scleroderma patients and 26 apparently healthy peoples, which were enrolled voluntarily in the study. Blood samples were taken from the three groups and analyzed to measure the serum levels of the three diagnostic tests.

Results

The sensitivities of the three tests were as the following: anti-cyclic citrullinated peptide antibodies 68.1%, rheumatoid factor IgM 78.7% and rheumatoid factor IgA 72.3%. There were no significant differences in sensitivities of the three tests and nearly all had the same sensitivity. The specificities of the three tests were as the following: anti-cyclic citrullinated peptide antibodies 97.6%, rheumatoid factor IgM 83.3% and rheumatoid factor IgA 90.5%. The specificity of anti-cyclic citrullinated peptide antibodies was significantly higher than rheumatoid factor IgM. There were no significant differences between the specificities of anti- cyclic citrullinated peptide antibodies and rheumatoid factor IgA, rheumatoid factor IgM and rheumatoid factor IgA. Therefore, the anti-cyclic citrullinated peptide antibodies give the best specificity among the three diagnostic tests; and they were positive in 40% of seronegative (rheumatoid factor IgM negative) rheumatoid patients.

Conclusion

Anti-cyclic citrullinated peptide antibodies are useful tools in the diagnosis of rheumatoid arthritis, as they are comparably sensitive as the rheumatoid factors but they have the advantage of possessing excellent specificity. Also they have an additional diagnostic value, as they are positive in 40% of seronegative rheumatoid patients.

KEYWORDS

Anti-cyclic citrullinated peptide antibodies, Rheumatoid factor IgM, Rheumatoid factor IgA.

References 

1. Olsen NJ, Stein CM. New drugs for rheumatoid arthritis. N Engl J Med. 2004 May 20; 350(21):2167-79.

2. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar; 31(3):315-24.

3. Dörner T, Egerer K, Feist E, Burmester GR. Rheumatoid factor revisited. Curr Opin Rheumatol. 2004 May; 16(3):246-53.

4. Hassfeld W, Steiner G, Hartmuth K, Kolarz G, Scherak O, Graninger W, et al. Demonstration of a new antinuclear antibody (anti-RA33) that is highly specific for rheumatoid arthritis. Arthritis Rheum. 1989 Dec; 32(12):1515-20.

5. Cordonnier C, Meyer O, Palazzo E, de Bandt M, Elias A, Nicaise P, et al. Diagnostic value of anti-RA33 antibody, antikeratin antibody, antiperinuclear factor and antinuclear antibody in early rheumatoid arthritis: comparison with rheumatoid factor. Br J Rheumatol. 1996 Jul;35 (7):620-4.

6. Simon M, Girbal E, Sebbag M, Gomès-Daudrix V, Vincent C, Salama G, et al. The cytokeratin filament-aggregating protein filaggrin is the target of the so-called "antikeratin antibodies," autoantibodies specific for rheumatoid arthritis. J Clin Invest. 1993 Sep;92(3):1387-93.

7. Bas S, Perneger TV, Seitz M, Tiercy JM, Roux-Lombard P, Guerne PA. Diagnostic tests for rheumatoid arthritis: comparison of anti-cyclic citrullinated peptide antibodies, anti-keratin antibodies and IgM rheumatoid factors. Rheumatology (Oxford). 2002 Jul;41(7):809-14.

8. Nijenhuis S, Zendman AJ, Vossenaar ER, Pruijn GJ, vanVenrooij WJ. Autoantibodies to citrullinated proteins in rheumatoid arthritis: clinical performance and biochemical aspects of an RA-specific marker. Clin Chim Acta. 2004 Dec;350(1-2):17-34.

9. van Venrooij WJ, Vossenaar ER, Zendman AJ. Anti-CCP antibodies: the new rheumatoid factor in the serology of rheumatoid arthritis. Autoimmun Rev. 2004 Jun;3 Suppl 1:S17-9.

10. Zendman AJ, Vossenaar ER, van Venrooij WJ. Autoantibodies to citrullinated (poly)peptides: a key diagnostic and prognostic marker for rheumatoid arthritis.  Autoimmunity. 2004 Jun;37(4):295-9.

11. Al Rawi ZS, Al Shackarchi HA, Marjana NH, Hart FD. Reumatoid arthritis in Iraq. Rheumatol Rehabil. 1977 May;16(2):128-32.

12. Avouac J, Gossec L, Dougados M. Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review. Ann Rheum Dis 2006; 65: 845–851.

13. Sauerland U, Becker H, Seidel M, Schotte H, Willeke P, Schorat A, et al. Clinical utility of the anti-CCP assay: experiences with 700 patients. Ann N Y Acad Sci. 2005; 1050:314-8.

14. Choi SW, Lim MK, Shin DH, Park JJ, Shim SC. Diagnostic performances of anti-cyclic citrullinated peptides antibody and antifilaggrin antibody in Korean patients with rheumatoid arthritis. J Korean Med Sci. 2005; 20:473-8.

15. De Rycke L, Peene I, Hoffman IE, Kruithof E, Union A, Meheus L, et al. Rheumatoid factor and anticitrullinated protein antibodies in rheumatoid arthritis: diagnostic value, associations with radiological progression rate, and extraarticular manifestations. Ann Rheum Dis. 2004; 63:1587-93.

16. Girelli F, Foschi FG, Bedeschi E, Calderoni V, Stefanini GF, Martinelli MG. Is anti cyclic citrullinated peptide a useful laboratory test for the diagnosis of rheumatoid arthritis? Allerg Immunol (Paris). 2004; 36:127-30.

17. Grootenboer-Mignot S, Nicaise-Roland P, Delaunay C, Meyer O, Chollet-Martin S, Labarre C. Second generation anti-cyclic citrullinated peptide (anti-cyclic citrullinated peptide antibodies) antibodies can replace other anti-filaggrin antibodies and improve rheumatoid arthritis diagnosis. Scand J Rheumatol. 2004; 33:218-20.

18. Dubucquoi S, Solau-Gervais E, Lefranc D, Marguerie L, Sibilia J, Goetz J, et al. Evaluation of anti-citrullinated filaggrin antibodies as hallmarks for the diagnosis of rheumatic diseases. Ann Rheum Dis. 2004; 63:415-9.

19. Vallbracht I, Rieber J, Oppermann M, Fo¨rger F, Siebert U, Helmke K. Diagnostic and clinical value of anti-cyclic citrullinated peptide antibodies compared with rheumatoid factor isotypes in rheumatoid arthritis. Ann Rheum Dis. 2004; 63:1079-84.

20. Rantapaa-Dahlqvist S, de Jong BA, Berglin E, Hallmans G, Wadell G, Stenlund H, et al. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum. 2003; 48:2741-9.

21. Greiner A, Plischke H, Kellner H, Gruber R. Association of anti-cyclic citrullinated peptide antibodies, anti-citrullin antibodies, and IgM and IgA rheumatoid factors with serological parameters of disease activity in rheumatoid arthritis. Ann N Y Acad Sci. 2005; 1050:295-303.

22. Lee DM, Schur PH. Clinical utility of the anti-CCP assay in patients with rheumatic diseases. Ann Rheum Dis. 2003; 62:870-4.

23. Prujin GJM, Vossenaar E R, Drijfhout JW, van Venrooij WJ and Zendman AJW. Anti-CCP antibody detection facilitates early diagnosis and prognosis of rheumatoid arthritis. Curr Rheumatol Rev. 2005; 1, 1-7.

24. Kwok JS, Hui KH, Lee TL, Wong W, Lau YL, Wong RW, et al. Anticyclic citrullinated peptide: diagnostic and prognostic values in juvenile idiopathic arthritis and rheumatoid arthritis in a Chinese population. Scand J Rheumatol. 2005; 34:359-66.

25. Raza K, Breese M, Nightingale P, Kumar K, Potter T, Carruthers DM, et al. Predictive value of antibodies to cyclic citrullinated peptide in patients with very early inflammatory arthritis. J Rheumatol. 2005; 32:231-8.

26. Vittecoq O, Incaurgarat B, Jouen-Beades F, Legoedec J, Letourneur O, Rolland D, et al. Autoantibodies recognizing citrullinated rat filaggrin in an ELISA using citrullinated and non-citrullinated recombinant proteins as antigens are highly diagnostic for rheumatoid arthritis. Clin Exp Immunol. 2004; 135:173-80.

27. Bas S, Genevay S, Meyer O, Gabay C. Anti-cyclic citrullinated peptide antibodies, IgM and IgA rheumatoid factors in the diagnosis and prognosis of rheumatoid arthritis. Rheumatology (Oxford). 2003; 42:677-80.

28. Vasiliauskiene L, Wiik A, Høier-Madsen M. Prevalence and clinical significance of antikeratin antibodies and other serological markers in Lithuanian patients with rheumatoid arthritis. Ann Rheum Dis. 2001; 60:459-66.