Anti-Cyclic Citrullinated Peptide Antibody and Rheumatoid Factor Isotypes in Iranian Patients with Rheumatoid Arthritis: Evaluation of Clinical Value and Association with Disease Activity
Abstract
In this study we determined the frequency, sensitivity and specificity of anti cyclic citrullinated peptides (anti-CCP) IgG antibody, total rheumatoid factor (RF-T), and RF isotypes in Iranian patients with rheumatoid arthritis (RA) and their association with age, clinical and serological parameters.
Anti-CCP and RF-T and RF isotypes level were measured in 418 patients and 399 healthy controls by enzyme-linked immunosurbant assay (ELISA). Additionally, serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), visual analog scale (VAS) and disease activity score (DAS28) were evaluated in RA patients.
The anti-CCP was positive in 53.1% of RA patients and 4.7% of controls. The frequency of RF-T was 61.87% and 17.66% in RA patients and controls respectively. The prevalence of RF isotypes in RA patients was 46.52% for RF-IgM, 23.47% for RF-IgA and 21.74% for RF-IgG.
31.39% of RA patients were RF-IgM positive without RF-IgA and RF-IgG and 21.9% were positive for all three RF classes. The anti-CCP positive patients showed increased number of swollen joints. On the other hand, RF-T positive patients exhibited a longer disease duration, lower age of onset and also higher ESR, CRP level and increased swollen joints. RF-T titer was significantly higher in RA patients with active disease compared to remission, low and moderate active groups. The sensitivity and specificity were 53.1, 95.3 for anti-CCP antibody and 61.8, 82.3 for RF-T.
Our results support that anti-CCP and RF titer maybe valuable in estimation of disease activity and other inflammatory parameters in RA patients.
1. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med 2011; 365(23):2205-19.
2. Song YW, Kang EH. Autoantibodies in rheumatoid arthritis: rheumatoid factors and anticitrullinated protein antibodies. QJM 2010; 103(3):139-46.
3. Lee AN, Beck CE, Hall M. Rheumatoid factor and anti- CCP autoantibodies in rheumatoid arthritis: a review. Clin Lab Sci 2008; 21(1):15-8.
4. Conrad K, Roggenbuck D, Reinhold D, Dörner T.Profiling of rheumatoid arthritis associated autoantibodies. Autoimmun Rev 2010; 9(6):431-5.
5. Vencovský J, Machácek S, Sedová L, Kafková J, Gatterová J, Pesáková V, et al. Autoantibodies can be prognostic markers of an erosive disease in early rheumatoid arthritis. Ann Rheum Dis 2003; 62(5):427-30.
6. Berglin E, Johansson T, Sundin U, Jidell E, Wadell G, Hallmans G, et al. Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies against cyclic citrullinated peptide before and at disease onset, and by IgA-RF at disease onset. Ann Rheum Dis 2006;65(4):453-8.
7. Lindqvist E, Eberhardt K, Bendtzen K, Heinegård D, Saxne T. Prognostic laboratory markers of joint damage in rheumatoid arthritis. Ann Rheum Dis 2005; 64(2):196-201.
8. Zeng X, Ai M, Tian X, Gan X, Shi Y, Song Q, et al.Diagnostic value of anti-cyclic citrullinated Peptide antibody in patients with rheumatoid arthritis. J Rheumatol 2003; 30(7):1451-5.
9. Heidari B, Firouzjahi A, Heidari P, Hajian K. The prevalence and diagnostic performance of anti-cyclic citrullinated peptide antibody in rheumatoid arthritis: the predictive and discriminative ability of serum antibody level in recognizing rheumatoid arthritis. Ann Saudi Med 2009, 29(6):467-70.
10. Rantapää-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(10):2741-9.
11. Singwe-Ngandeu M, Finckh A, Bas S, Tiercy JM, Gabay C. Diagnostic value of anti-cyclic citrullinated peptides and association with HLA-DRB1 shared epitope alleles in African rheumatoid arthritis patients. Arthritis Res Ther 2010; 12(2):R36.
12. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010;62(9):2569-81.
13. 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; 31(3):315-24.
14. van Gestel AM, Prevoo ML, van 't Hof MA, van Rijswijk MH, van de Putte LB, van Riel PL. Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism Criteria. Arthritis Rheum 1996; 39(1):34-40.
15. van Vollenhoven, RF. Sex differences in rheumatoid arthritis: more than meets the eye. BMC Med, 2009; 7:12.
16. Sockalingam S, Khuan CS, Sthaneshwar P. Prevalence of anti cyclic citrullinated peptide antibodies in Malaysian rheumatoid arthritis patients and its correlation with disease activity. Int J Rheum Dis 2009; 12(3):211-5.
17. Sihvonen S, Korpela M, Mustila A, Mustonen J. The predictive value of rheumatoid factor isotypes, anti-cyclic citrullinated peptide antibodies, and antineutrophil cytoplasmic antibodies for mortality in patients with rheumatoid arthritis. J Rheumatol 2005; 32(11):2089-94.
18. Jaskowski TD, Hill HR, Russo KL, Lakos G, Szekanecz Z, Teodorescu M. Relationship between rheumatoid factor isotypes and IgG anti-cyclic citrullinated peptide antibodies. J Rheumatol 2010; 37(8):1582-8.
19. Mimori T. Clinical significance of anti-CCP antibodies in rheumatoid arthritis. Intern Med 2005; 44(11):1122-6.
20. 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.
Files | ||
Issue | Vol 13, No 3 (2014) | |
Section | Articles | |
Keywords | ||
Anti-CCP C-Reactive Protein Disease Activity Rheumatoid Arthritis Rheumatoid Factor |
Rights and permissions | |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |