|Year : 2011 | Volume
| Issue : 2 | Page : 195-196
A combined diagnostic approach to Rheumatoid arthritis using anti-cyclic citrullinated peptide antibodies and rheumatoid factor
S Oommen, B Appalaraju, S Sivadarshini, Jayashree
Department of Microbiology, PSG Institute of Medical Sciences and Research Centre, Peelameedu, Coimbatore - 641 004, Tamil Nadu, India
|Date of Submission||24-Oct-2010|
|Date of Acceptance||30-Jan-2011|
|Date of Web Publication||2-Jun-2011|
Department of Microbiology, PSG Institute of Medical Sciences and Research Centre, Peelameedu, Coimbatore - 641 004, Tamil Nadu
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Oommen S, Appalaraju B, Sivadarshini S, Jayashree. A combined diagnostic approach to Rheumatoid arthritis using anti-cyclic citrullinated peptide antibodies and rheumatoid factor. Indian J Med Microbiol 2011;29:195-6
|How to cite this URL:|
Oommen S, Appalaraju B, Sivadarshini S, Jayashree. A combined diagnostic approach to Rheumatoid arthritis using anti-cyclic citrullinated peptide antibodies and rheumatoid factor. Indian J Med Microbiol [serial online] 2011 [cited 2020 May 28];29:195-6. Available from: http://www.ijmm.org/text.asp?2011/29/2/195/81782
Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease, most often involving the small joints of the hands and feet, although any synovial joint can be affected. It affects 1-2% of the world population with a female-to-male ratio of 2.5:1.  Recognition of RA as early as possible is important, not only because a significant proportion of the patients develops irreversible joint damage shortly after disease onset  but also because of the risks associated with its treatment.  The diagnosis of RA depends primarily on the American College of Rheumatology (ACR) 1987 revised criteria.  A patient is considered to have RA if at least four of the seven criteria have been present for at least six weeks; of which the only laboratory test criterion is the presence of serum Rheumatoid Factor (RF).
In established disease, IgM- RF can be detected with a sensitivity of 60-70% and a specificity of 80-90%.  Another antibody against the cyclic citrulline protein (CCP) specific for RA was discovered later.  Despite overwhelming evidence of its specificity, anti-CCP antibody detection for the diagnosis of RA is not requested on a regular basis in our country probably due to the lack of comparative studies or the non-availability of this test in routine laboratories. This study aims to explore the alternative and additional diagnostic value of anti-CCP antibodies compared with RF in the diagnosis of early RA.
This prospective study, which was carried out for a period of eight months in a tertiary care hospital included 93 consecutive patients with recent-onset arthritis for at least six weeks. Patients who had been previously treated for RA and juvenile arthritis were excluded. Blood was collected with informed consent and serum was subjected to RF detection (turbidometry, Quantia, Tulip diagnostics) and anti-CCP antibody detection by enzyme linked immunosorbent assay (ELISA) (Immunoscan, Eurodiagnostica) with the cut-off at 10 IU/ml and 25 Units/ml respectively. Basic demographic and disease-related details regarding clinical and radiological signs and treatment received and outcome were noted. Sensitivity and specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for each of the tests were calculated using SPSS statistical software Version 11.5.
Of the 93 patients, 22 patients were finally diagnosed as having RA by the ACR 1987 revised criteria.  Anti-CCP antibody was positive in 81.8% of these patients with titres equal to or above 800 units/ml while RF was positive in 77.2% [Table 1]. In a meta-analysis published in 2007 it was found that anti-CCP antibody displays sensitivities comparable to that of RF (approximately 80%) but with superior specificity (98%).  In our study too, the sensitivity of anti-CCP antibody (81%) was comparable with that of RF (77%) but the specificity was much better 98% in contrast to RF (76%). The PPV and NPV was 94% for anti-CCP in contrast to RF which was 50% and 91% respectively. RF is often detected in other conditions associated with chronic inflammation (e.g., lupus, primary Sjogren's syndrome, chronic osteomyelitis) and in up to 10% of the general population (usually in low titres).  Anti-CCP antibody represents a superior serological marker for RA as it is highly specific for the disease, , able to distinguish RA from other arthritides that mimic RA,  detectable very early in disease , and also helpful in predicting disease outcome  thus helping in earlier and focussed anti-rheumatoid therapy. Thus anti-CCP antibody detection may be used in combination with RF for an optimal early diagnostic strategy of RA.
| ~ References|| |
|1.||Wright PE. Rheumatoid Arthritis. In: Canale T, Beaty JH, editors. Campbell's Operative Orthop. 11 th ed, Vol. 2. Chapter 70. Pennsylvania, Philadelphia: Mosby Elsevier; 2008. |
|2.||Van Gaalen FA, LinnRasker SP, Van Venrooij WJ, de Jong BA, Breedveld FC. Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: A prospective cohort study. Arthritis Rheum 2004;50:709-15. |
|3.||El-Gabalawy HS, Duray P, Goldbach-Mansky R. Evaluating patients with arthritis of recent onset: Studies in pathogenesis and prognosis. JAMA 2000284:2368-73. |
|4.||Pruijn JM, Vossenaar ER, 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 |
|5.||Symmons DP. Classification criteria for rheumatoid arthritis-time to abandon rheumatoid factor? Rheumatology 2007;46:725-6. |
|6.||Nishimura K, Sugiyama D, Kogata Y, Tsuji G, Nakazawa T, Kawano S, et al. Meta-analysis: Diagnostic Accuracy of Anti-Cyclic Citrullinated Peptide Antibody and Rheumatoid Factor for Rheumatoid Arthritis. Ann Intern Med 2007;146:797-808. |
|This article has been cited by|
||Citrulline: pharmacological perspectives and its role as an emerging biomarker in future
| ||Shilpa N. Kaore,Hanmant S. Amane,Navinchandra M. Kaore |
| ||Fundamental & Clinical Pharmacology. 2013; 27(1): 35 |
|[Pubmed] | [DOI]|