Please enter verification code
A Study on the Importance of Anti Cyclic Cytrullinated Peptide Antibodies (Anti-CCP) and Rheumatoid Factor (RF) Assay in Detection of Patients with Rheumatoid Arthritis in North Eastern Part of India
International Journal of Immunology
Volume 4, Issue 5, October 2016, Pages: 27-34
Received: Oct. 15, 2016; Accepted: Oct. 31, 2016; Published: Nov. 23, 2016
Views 4316      Downloads 134
Anindya Das, Department of Microbiology, Gauhati Medical College and Hospital, Guwahati, India
Chimanjita Phukan, Department of Microbiology, Gauhati Medical College and Hospital, Guwahati, India
Chitralekha Baruah, Department of Medicine, Gauhati Medical College and Hospital, Guwahati, India
Article Tools
Follow on us
Objective: Rheumatoid arthritis (RA) is a polyarticular and systemic chronic inflammatory autoimmune disease, occurring throughout the world. The aim of the present study is to observe the role of anti-CCP antibody and Rheumatoid Factor (RF) assay in diagnosing patients of rheumatoid arthritis in north-eastern part of India, in the state of Assam and also to evaluate the individual and combined sensitivity and specificity of anti-CCP antibody and RF assay in diagnosing RA. Methods: A total of 88 cases presenting with history of polyarthritis were included in the study of which the study group comprised of 57 clinically diagnosed cases of rheumatoid arthritis and control group comprised of 31 patients of non-RA rheumatic diseases having joint pain. Individual sensitivity and specificity of the above tests, and also the combined specificity of the two tests and also the three tests were calculated and the results of the tests were compared with each other to examine the correlation between them. Results: Sensitivity of anti-CCP ELISA, RF IgM ELISA and RF Latex test was 91.23%, 75.44% and 40.35% with specificity of 70.97%, 67.74% and 90.32% respectively. If the three tests are combined then the combined specificity of the three tests is 99.59%. One important observation was that out of 9 anti-CCP positive cases in the control group(n = 31) 5 cases were weakly positive (titer 6.25 – 20 U/ml), considering cut-off value 6.25 U/ml as mentioned by the kit.If these weakly positive cases in the control group are considered as negative, then specificity of anti-CCP ELISA increases from 70.97% to 87.1% which is more acceptable. Conclusion: From this study it is observed that anti-CCP antibodies are highly sensitive and specific for diagnosing RA. If this test is combined with RF IgM ELISA and Latex test then combined specificity can be increased more than 99%. However, weakly positive titers of anti-CCP antibodies are more prevalent in other non-RA rheumatic diseases in North-Eastern part of India.
Anti-CCP Antibody, Rheumatoid Factor, Latex Agglutination Test, Combined Specificity, Resultant Sensitivity, Enzyme Linked Immunosorbent Assay (ELISA), Cut-Off Value
To cite this article
Anindya Das, Chimanjita Phukan, Chitralekha Baruah, A Study on the Importance of Anti Cyclic Cytrullinated Peptide Antibodies (Anti-CCP) and Rheumatoid Factor (RF) Assay in Detection of Patients with Rheumatoid Arthritis in North Eastern Part of India, International Journal of Immunology. Vol. 4, No. 5, 2016, pp. 27-34. doi: 10.11648/j.iji.20160405.11
Copyright © 2016 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Arnett FC, et al. The American Rheumatism Association 1987 revised criteria for the classification of Rheumatoid Arthritis. Arthritis Rheum 1988; 31: 315-324.
De Vries-Bouwastra JKD, Breedveld BAC, Ferdinand C. Biologics in early Rheumatoid Arthritis. Rheum Dis Clin North Am 2005; 31: 745-762
O’Dell JR. Treating Rheumatoid Arthritis early: a window of opportunity? Arthritis Rheum 2002;46:283-285.
Lee DM, Schur PH. Clinical utility of the anti-CCP assay in patients with rheumatic disease. Ann Rheum Dis 2003; 62:870-874.
Milgrom F. Development of rheumatoid factor research through 50 years. Scand J Rheumatol Suppl. 1988; 75: 2-12.
A J Soltys, J S Axford. Rheumatoid factors: where are we now?Ann Rheum Dis1997; 56:285-286.
Brian J. Sutton, Adam L. Corper, Maninder K. Sohi, Roy Jefferis, Dennis Beale, Michael J. Taussig. The Structure of a Human Rheumatoid Factor Bound to IgG Fc. Glycoimmunology 2Advances in Experimental Medicine and Biology 1998; 435: 41-50.
M. Herold, V. Boeser, E. Russe, & W. Klotz. Anti-CCP: History and its usefulness. Clinical & Developmental Immunology 2005; 2: 131–135.
Sebbag M, et al. The antiperinuclear factor and the so-called antikeratin antibodies are the same rheumatoid arthritis specific autoantibodies. J Clin Invest 1995; 95: 2672–2679.
Schellekens GA, et al. Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis specific autoantibodies. J Clin Invest 1998; 101: 273–281.
Alain Saraux et al. Value of Antibodies to Citrulline-containing Peptides for Diagnosing Early Rheumatoid Arthritis. The Journal of Rheumatology 2003; 30: 12.
Fariba Binesh, Hossein Soleimani Salehabadi, Nasim Behniafard, Kian Ranginkaman and NasrinBehniafard. A Comparative Assessment of the Diagnostic Value of Anti-cyclic Citrullinated Peptide Antibodies and Rheumatoid Factor in Rheumatoid Arthritis. J Clin Exp Pathol 2014; 4: 158.
Aflaky E, Shenavandeh S, Ashraf MJ. A comparison of performance of anti-cyclic citrullinated peptide 2 and citrullinated protein antibodies in the diagnosis of rheumatoid arthritis in Iranian patients. Rheumatol Int 2010; 30: 461-466.
Swedler W, Wallman J, Froelich CJ, Teodorescu M. Routine measurement of IgM, IgG, and IgA rheumatoid factors: high sensitivity, specificity, and predictive value for rheumatoid arthritis. J Rheumatol. 1997; 6:1037-44.
S. Bas, S. Genevay, O. Meyer and C. Gabay. Anti-cyclic citrullinated peptide antibodies, IgM and IgA rheumatoid factors in the diagnosis and prognosis of rheumatoid arthritis. Rheumatology 2003; 5: 677-680.
T. B. Niewold, M. J. Harrison, and S. A. Paget. Anti-CCP antibody testing as a diagnostic and prognostic tool in rheumatoid arthritis. Q J Med 2007; 100:193–201.
Gupta, Rajiv; Thabah, Molly M.; Aneja, Ritu; Kumar, Ashok; Varghese, Titus; Chandrasenan, P. J. Usefulness of Anti-CCP antibodies in rheumatic diseases in Indian patients. Indian Journal of Medical Sciences.2009; 3:92.
Schellekens GA, Visser H, de Jong BA, van den Hoogen FH, HazesJM, Breedveld FC, van Venrooij WJ. The diagnostic properties of rheumatoid arthritis antibodies recognizing a cycliccitrullinated peptide. Arthritis Rheum 2000; 43:155–163.
Goldbach-Mansky R, Lee J, McCoy A, Hoxworth J, YarboroC,Smolen JS, Steiner G, Rosen A, Zhang C, Menard HA, Zhou ZJ, Palosuo T, Van Venrooij WJ, Wilder RL, KlippelJH, Schumacher HR Jr, El-Gabalawy HS. Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset. Arthritis Res. 2000; 2:236–243.
Bizzaro N, Mazzanti G, Tonutti E, Villalta D, Tozzoli R. Diagnostic accuracy of the anti-citrulline antibody assay for rheumatoid arthritis. ClinChem 2001; 47:1089–1093.
Walther J, van Venrooij, Joyce J, B. C. van Beers and Ger J. M. Pruijn. Anti-CCP antibodies: the past, the present and the future. Nat. Rev. Rheumatol2011; 7: 391–398.
Suzuki K, Sawada T, Murakami A, Matsui T, Tohma S, NakazonoK, Takemura M, Takasaki Y, Mimori T, Yamamoto K. High diagnostic performance of ELISA detection of antibodies to citrullinated antigens in rheumatoid arthritis. Scand J Rheumatol 2003; 32: 197–204.
Mimori T. Clinical significance of anti-CCP antibodies in rheumatoid arthritis. Intern Med 2005; 44: 1122-1126.
Suzuki A, et al: Functional haplotypes of PADI4, encoding citrullinating enzyme peptidyl arginine deiminase4, are associated with rheumatoid arthritis. Nat Genet.2003; 34: 395.
Barton A, et al: A functional haplotype of the PADI4gene associated with rheumatoid arthritis in a Japanese population is not associated in a United Kingdom population. Arthritis Rheum. 2004; 50: 1117.
Vossenaar, E. R. et al. The presence of citrullinated proteins is not specific for rheumatoid synovial tissue. Arthritis Rheum 2004; 50: 3485–3494.
Münevver Serdaroğlu, Haşim Çakırbay, Orhan Değer, Sevil Cengiz, and Sibel Kul. The association of anti-CCP antibodies with disease activity in rheumatoid arthritis. Rheumatol Int. 2008;10: 965–970.
Rajul Parikh, Annie Mathai, Shefali Parikh, G Chandra Sekhar, and Ravi Thomas, Understanding and using sensitivity, specificity and predictive values. Indian J Ophthalmol. 2008; 1: 45–50.
Dennis L. Kasper, et al. Harrison’s Principles of Internal Medicine, 19th edition, vol 2, 380:2136-2149.
Science Publishing Group
1 Rockefeller Plaza,
10th and 11th Floors,
New York, NY 10020
Tel: (001)347-983-5186