Diagnostic value of third generation anti-cyclic citrullinated peptide antibody (Anti-CCP3) assay in rheumatoid arthritis patients
A cross sectional observational study
Keywords:
anti-cyclic citrullinated, peptide antibodies, rheumatoid arthritis, diagnostic biomarker, ACPAAbstract
Objective: To evaluate the efficacy of anti-CCP3 as a diagnostic marker in Egyptian early rheumatoid arthritis patients. Subjects and Methods: A total of 60 rheumatoid arthritis patients and 30 aged and sex matched volunteers participated in the study. Basic demographic, functional and clinical data were collected alongside laboratory assessment of Anti-cyclic citrullinated peptide 3 (Anti-CCP3) by ELISA. Results: Anti-CCP3 level was significantly higher in RA patients compared to controls (p 0.001) .At cut off value 20.65 (U/mL) and AUC 0.950, Anti-CCP 3 could significantly distinguish between RA patients and controls (p 0.001) .The sensitivity and specificity were 83.33%, and 93.33% respectively. Also, Anti-CCP 3 levels significantly correlated with the number of swollen and tender joints (P 0.05), VAS (P 0.05), DAS-28 (P 0.05), m HAQ (P 0.001), bone erosions (P 0.001), and narrow joint space (P 0.001). Conclusion: Anti-CCP3 is a potent diagnostic as well as prognostic laboratory marker and its positivity resulted in more specific identification of RA patients. Moreover, anti-CCP3 is considered the most acceptable choice for diagnosing early rheumatoid arthritis especially sero-negative type, with 83.33% sensitivity and 93.33% specificity.
Downloads
References
Shrivastava AK, Pandey A Inflammation and rheumatoid arthritis. J Physiol Biochem. 2013; 69:335-347.
Dos Anjos LM, Pereira IA, d 'Orsi E et al: A comparative study of IgG second- and third-generation anti-cyclic citrullinated peptide (CCP) ELISAs and their combination with IgA third-generation CCP ELISA for the diagnosis of rheumatoid arthritis. Clin Rheumatol; 28:153-158 (2009).
Neogi T, Aletaha D, Silman AJ, et al. The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis: Phase 2 methodological report. Arthritis Rheum. 2010; 62:2582-2591.
Van L, Renskers L. The Disease Activity Score (DAS) and the Disease Activity Score using 28 joint counts (DAS28) in the management of rheumatoid arthritis. Clin Exp Rheumatol. 2016; 34:40-44.
Ono K, Ohashi S, Oka H, et al. The impact of joint disease on the Modified Health Assessment Questionnaire scores in rheumatoid arthritis patients: A cross-sectional study using the National Database of Rheumatic Diseases by iR-net in Japan. Mod Rheumatol. 2016; 26:529-533.
Akkececi NS, Cetin GY, Gogebakan H, et al. The C-reactive protein/albumin ratio and complete blood count parameters as indicators of disease activity in patients with Takayasu arteritis. Med Sci Monit. 2019; 25:1401.
Ying P, Lu T, Xu Y, et al. Preoperative erythrocyte sedimentation rate in patients with rheumatoid arthritis predicts deep vein thrombosis following total knee arthroplasty. Clin Hemorheol Microcirc. 2021;1-9.
Tyker A, Ventura IB, Lee CT, et al. High-titer rheumatoid factor seropositivity predicts mediastinal lymphadenopathy and mortality in rheumatoid arthritis-related interstitial lung disease. Sci Rep. 2021; 11:1-8.
Khadim R, Al-Fartusie F. editors. Evaluation of Liver Function and Lipid profiles in Iraqi patients with Rheumatoid Arthritis. Journal of Physics: Conference Series; 2021; IOP Publishing: DOI:10.1088/1742-6596/1853/1/012040.
Chinnadayyala SR, Cho S. Electrochemical immunosensor for the early detection of rheumatoid arthritis biomarker: anti-cyclic citrullinated peptide antibody in human serum based on avidin-biotin system. Sensors. 2021; 21:124.
Demoruelle MK, Wang H, Davis RL, et al. Anti-peptidylarginine deiminase-4 antibodies at mucosal sites can activate peptidylarginine deiminase-4 enzyme activity in rheumatoid arthritis. Arthritis Res Ther. 2021; 23:1-8.
Salaffi F, Carotti M, Beci G, et al. Radiographic scoring methods in rheumatoid arthritis and psoriatic arthritis. Radiol Med. 2019; 124:1071-1086.
Hodkinson B, Meyer PWA, Musenge E, et al. The diagnostic utility of the anti-CCP antibody test is no better than rheumatoid factor in South Africans with early rheumatoid arthritis. Clinical Rheumatology. 2010;29(6):615-8.
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. Clinical Rheumatology. 2008; 27(1):77-83.
Vos I, Van Mol C, Trouw LA, et al. Anti-citrullinated protein antibodies in the diagnosis of rheumatoid arthritis (RA): diagnostic performance of automated anti-CCP-2 and anti-CCP-3 antibodies assays. Clinical Rheumatology. 2017; 36(7):1487-92.
Santiago M, Baron M, Miyachi K, Fritzler MJ, Abu-Hakima M, Leclercq S 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 2008; 27(1):77–83.
Wu R, Shovman O, Zhang Y, Gilburd B, Zandman-Goddard G, Shoenfeld Y. Increased prevalence of anti-third generation cyclic citrullinated peptide antibodies in patients with rheumatoid arthritis and CREST syndrome. Clin Rev Allergy Immunol 2007; 32(1):47–56.
Luis Caro-Oleas J, Fernández-Suárez A, Reneses Cesteros S, Porrino C, Núñes-Roldán A, Wichmann Schlipf I. Diagnostic usefulness of a third-generation anti-cyclic citrulline antibody test in patients with recent-onset polyarthritis. Clin Chem Lab Med 2007; 45(10):1396–401.
Lutteri L, Malaise M, Chapelle JP. Comparison of second- and third-generation anti-cyclic citrullinated peptide antibodies assays for detecting rheumatoid arthritis. Clin Chim Acta 2007; 386(1–2):76–81.
Szekanecz Z, Szabó Z, Zeher M, et al. Superior performance of the CCP3.1 test compared to CCP2 and MCV in the rheumatoid factor-negative RA population. Immunol Res. 2013;56(2-3):439-43.
Mutlu N, Bicakcigil M, Tasan DA, et al. Comparative performance analysis of 4 different anti-citrullinated protein assays in the diagnosis of rheumatoid arthritis. J Rheum.. 2009;36(3):491-500.
Predeteanu D, Varzaru L, Balanescu A, et al. Anti-cyclic citrullinated peptide antibodies--activity markers in rheumatoid arthritis. Journal of medicine and life. 2009;2(1):36-41.
Swart A, Burlingame RW, Gürtler I, et al. Third generation anti-citrullinated peptide antibody assay is a sensitive marker in rheumatoid factor negative rheumatoid arthritis. Clinica chimica acta. 2012;414:266-72.
Sockalingam S, Khuan CS and Sthaneshwar P. Prevalence of anticyclic citrullinated peptide antibodies in Malaysian rheumatoid arthritis patients and its correlation with disease activity. Int. J. Rheum. 2009, 12: 211-5.
Onder B, Kurtaran A, Kimyon S, Selcuk B and Akyuz, M. Association of anti-CCP positivity with serum ferritin and DAS-28. Rheumatol Int.2009;30: 223-7.
Shah B G , Quershi H.J, Zafar U. Serum Anti-CCP Antibody and its Correlation with Disease Activity in Local Pakistani Rheumatoid Arthritis Patients. Pak J. Med and Health Sci. 2014, ( 8); 1041-44.
Vanichapuntu M, Phuekfon P, Suwannalai P, Verasertniyom O, Nantiruj K. and Janwityanujit, S. Are anti-citrulline autoantibodies better serum markers for rheumatoid arthritis than rheumatoid factor in Thai population? Rheumatol Int.2010;30: 755-9.
Rydell E, Forslind K, Nilsson J-Å, et al. Predictors of radiographic erosion and joint space narrowing progression in patients with early rheumatoid arthritis: a cohort study. Arthritis research & therapy. 2021;23(1):1-13.
Yee A, Webb T, Seaman A, et al. Anti-CarP antibodies as promising marker to measure joint damage and disease activity in patients with rheumatoid arthritis. Immunologic research. 2015;61(1):24-30.
Chen Z, Fang W, Qin Y, et al. Citrullinated Antigens with Multiple Citrulline Similar Motif in the Diagnosis of Rheumatoid Arthritis: A Preliminary Single-Center Study. Journal of Immunology Research. 2021;2021.
Kroot E, De Jong B, Van Leeuwen M, et al. The prognostic value of anti-cyclic citrullinated peptide antibody in patients with onset rheumatoid arthritis. Arthritis Rheum 2000; 43: 1831-35 22.
Forslind K, Ahlmen M, Eberhardt K, Hafstrom I, Svensson B. Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: role of antibodies to citrullinated peptides (anti-CCP). Ann Rheum Dis 2004; 63:1090-95
Published
How to Cite
Issue
Section
Copyright (c) 2023 International journal of health sciences

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Articles published in the International Journal of Health Sciences (IJHS) are available under Creative Commons Attribution Non-Commercial No Derivatives Licence (CC BY-NC-ND 4.0). Authors retain copyright in their work and grant IJHS right of first publication under CC BY-NC-ND 4.0. Users have the right to read, download, copy, distribute, print, search, or link to the full texts of articles in this journal, and to use them for any other lawful purpose.
Articles published in IJHS can be copied, communicated and shared in their published form for non-commercial purposes provided full attribution is given to the author and the journal. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
This copyright notice applies to articles published in IJHS volumes 4 onwards. Please read about the copyright notices for previous volumes under Journal History.








