Diagnostic Performance of Anti-Cyclic Citrullinated Peptide Antibodies in Rheumatoid Arthritis and Other Rheumatological Disorders (original) (raw)

"Association of Anti-CCP Antibodies with Disease Activity in Rheumatoid Arthritis"

Background: Rheumatoid arthritis (RA) is an autoimmune disease and it is characterized by the production of autoantibodies specific for the disease like rheumatoid factor, antibodies against cyclic citrullinated peptides (Anti-CCP), antinuclear autoantibodies (ANA) etc. We have very few specific data regarding these issues.. In total 165 patients with RA attended the mentioned units with proper documents were finalized as the study population. A pre-designed semi-structured questioner was used in collecting patient data. All data were collected, processed, analyzed and disseminated by MS-Office and SPSS version 20 as per need. Result: In this study, the DAS 28 score was significantly higher in anti-CCP positive patients than anti-CCP negative patients (6.3±0.92 vs. 5.9±0.8, p = 0.017). The number of tender joint count and swollen joint count were significantly higher in the anti-CCP positive group than those in the anti-CCP negative group (31±12 vs. 24±12, p=0.003; 6±5 vs. 3±2, p=0.002 respectively). ESR (mean±SD) was 61.7±31.4 in Anti-CCP positive group and 48.9±19.6 in Anti-CCP negative group, which was significantly higher in the Anti-CCP positive group (P=0.032). Anaemia was significantly higher in Anti-CCP positive group (55.3% vs. 33.3%, p=0.023). Patient's global assessment of disease activity and physician's global assessment of disease activity were also higher in the Anti-CCP positive group than negative group, which was nearly significant (57.0±15.4 vs. 52.7±9.8, p-0.054; 51.0±15.6 vs. 45.2±12.5, p= 0.053 respectively). On the other hand, there was no statistically significant difference in term of disease duration, VAS, HAQ, morning stiffness > 60 minutes, CRP, Haemoglobin, platelet count and joint deformity (p> 0.05). In comparison of disease activity indices level between Anti-CCP positive and negative patients with RA we observed DAS 28 was not associated with anti-CCP positivity (P=0.410), HAQ score < 1 was significantly less in patients with anti-CCP negativity (P=0.02), patient's global assessment and physician's global assessment score were much higher in the anti-CCP positive group and number of tender joint count was significantly higher in the former group. Conclusion: Anti-CCP antibodies test should be continued for diagnosis of rheumatoid arthritis especially for the RF negative rheumatoid arthritis patients. Anti-CCP antibody test does not appear to be useful as a marker of disease activity in rheumatoid arthritis.

Anticyclic Citrullinated Peptide Antibodies in Rheumatoid and Nonrheumatoid Rheumatic Disorders: Experience with 1162 Patients

The Journal of Rheumatology, 2014

Anticyclic citrullinated peptide antibodies (anti-CCP) are considered specific markers of rheumatoid arthritis (RA) and have been included in the revised classification criteria for RA diagnosis. However, these antibodies have also been detected in patients with other types of chronic inflammatory rheumatism. Our objectives were to identify the prevalence of positive anti-CCP patients in non-RA diseases, to determine the diagnostic value of anti-CCP for the diagnosis of RA, to specify the clinical characteristics of non-RA patients positive for anti-CCP, and to determine the discriminatory value of the levels of anti-CCP in patients among the various diseases. Methods. We carried out an observational and descriptive study. All the determinations of anti-CCP requested by the 2 rheumatology departments at Cochin Hospital over a period of 18 months were analyzed. Such determinations were requested for 1162 patients in total. Anti-CCP levels were determined with the Euro Diagnostica ELISA kit, with values ≥ 25 U for this test being considered positive. The diagnosis of rheumatic conditions was the responsibility of the treating physician. Results. Anti-CCP antibodies were detected in 357 (30.7%) of the 1162 patients. The prevalence of anti-CCP was 292/417 (70.0%) in RA, 13/122 (10.6%) in patients with psoriatic arthritis, 13/62 (20.9%) in patients with unclassified rheumatism, 11/33 (33.3%) in patients with primary Sjögren syndrome, 5/30 (16.6%) in patients with systemic lupus erythematosus, 3/28 (10.7%) in patients with mixed connective tissue disorder, 3/36 (8.3%) in patients with systemic sclerosis, 7/44 (15.9%) in patients with juvenile arthritis, and 6/220 (2.7%) in patients with noninflammatory diseases. In the population of patients positive for anti-CCP, mean anti-CCP levels were 869.4 (± 978.4) U/ml, with no significant difference between RA [854.8 (± 959.8) U/ml] and any of the non-RA conditions [922.7 (± 1070.0) U/ml]. Conclusion. Anti-CCP are a hallmark of RA, but may be observed in other inflammatory, systemic, or mechanical diseases. In this large cohort of patients, the presence of second-generation anti-CCP (anti-CCP2) antibodies is useful in diagnosing RA (70% sensitivity, 91.3% specificity), but examining the levels of these antibodies does not appear to offer further discriminatory power among patients who are anti-CCP2-positive.

The association of anti-CCP antibodies with disease activity in rheumatoid arthritis

Rheumatology International, 2008

Antibodies to citrullinated proteins have been described in patients with rheumatoid arthritis (RA) and these appear to be the most speciWc markers of the disease. Our objective was to determine the frequency of antibodies to cyclic citrullinated peptides (CCPs) in patients with RA and the association of anti-CCP antibodies with disease activity, radiological erosions and HLA DR genotype. Forty patients with RA and 38 patients with Wbromyalgia were included in this study. Serum samples were collected from both patient groups with RA and Wbromyalgia. Anti-CCP was measured by the corresponding enzyme-linked immunosorbent assay. Additionally, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), disease activity score (DAS), visual analog scala (VAS), HLA genotype and radiographic information were determined in patients with RA. The rate of sensitivity and speciWcity of anti-CCP reactivity for the diagnosis RA were measured (sensitivity 50%, speciWcity100%). There is no signiWcant diVerence between anti-CCP (+) and anti-CCP (¡) RA patients for DAS28, VAS, ESR, CRP, disease duration, HLA genotype, and radiological assessment of hand. However, there was a signiWcant diVerence between anti-CCP (+) and anti-CCP (¡) RA patients for RF and the radiological assessment of left and right wrists (respectively, P < 0.05, P = 0.04, P = 0.01). There was no signiWcant correlation between anti-CCP antibody and ESR, CRP, VAS, DAS 28 or radiological assessment. A small but signiWcant correlation was found between RF and anti-CCP antibody (P = 0.02, r = 0.35).

Evaluation of anti-CCP antibody for diagnosis of rheumatoid arthritis

Clinical laboratory, 2011

Rheumatoid arthritis is a common, world wide, systemic disease that affects mainly joints. Rheumatoid factor is the only marker to diagnose rheumatoid arthritis; however these antibodies are present in other disorders and even in up to 15% of the healthy population. Many auto antibodies have been reported to diagnose rheumatoid arthritis e.g. APF and AKA, etc. but they are not specific and due to tedious laboratory procedure, they have not been generally adopted. Anti-CCP antibodies have been reported for their high sensitivity and specificity. This study was planed to determine the prevalence of anti-CCP antibodies and RA factor in clinically diagnosed patients of rheumatoid arthritis. Anti-CCP antibody was determined by ELISA technique and RA-factor was done by latex agglutination method. Forty five patients, 36 female and 9 male, were recruited for this study. Twenty-five (55.6%) patents were positive for anti-CCP antibodies while 20 patients were negative for anti-CCP antibodies...

Diagnostic value of anti-cyclic citrullinated peptide antibodies in Greek patients with rheumatoid arthritis

BMC Musculoskeletal Disorders, 2007

Background Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been of diagnostic value in Northern European Caucasian patients with rheumatoid arthritis (RA). In these populations, anti-CCP antibodies are associated with the HLA-DRB1 shared epitope. We assessed the diagnostic value of anti-CCP antibodies in Greek patients with RA where the HLA shared epitope was reported in a minority of patients. Methods Using an enzyme-linked immunosorbent assay (ELISA) (CCP2) kit, we tested anti-CCP antibodies in serum samples from 155 Greek patients with RA, 178 patients with other rheumatic diseases, and 100 blood donors. We also determined rheumatoid factor (RF) and compared it to anti-CCP antibodies for area under the curve (AUC), sensitivity, specificity and likelihood ratios. Results Sensitivity of anti-CCP2 antibodies and RF for RA was 63.2% and 59.1%, and specificity was 95.0% and 91.2%, respectively. When considered simultaneously, the AUC for anti-CCP antibodies was 0.90 with 95% CI of 0.87 to 0.93 and the AUC for RF was 0.71 with 95% CI of 0.64 to 0.77. The presence of both antibodies increased specificity to 98.2%. Anti-CCP antibodies were positive in 34.9% of RF-negative RA patients. Anti-CCP antibodies showed a correlation with the radiographic joint damage. Anti-CCP-positive RA patients had increased the swollen joint count and serum CRP concentration compared to anti-CCP-negative RA patients (Mann-Whitney U test, p = 0.01, and p < 0.001, respectively). However, no correlation was found between anti-CCP antibodies and DAS28 score (r = 0.13, p = 0.12). Conclusion In Greek patients with RA, anti-CCP2 antibodies exhibit a better diagnostic value than RF and a correlation with radiological joint damage and therefore are useful in everyday rheumatology practice.

Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review

Annals of the Rheumatic Diseases, 2005

To evaluate the two generations of anti-cyclic citrullinated protein (CCP) antibodies as a diagnostic marker of rheumatoid arthritis (RA) and as a predictor of future development of RA in healthy subjects and in patients with early undifferentiated arthritis. Methods: A systematic analysis of the literature published between 1999 and February 2006 was conducted. Data were collected on the sensitivity and specificity of the two generations of anti-CCP antibodies for diagnosing RA and predicting future development of the disease. Results: Among 107 studies initially identified, 68 had interpretable data and were analysed. Diagnostic properties were assessed in 58 studies: mean (SD) sensitivity was 53 (10)% (range 41-68) and 68 (15)% (range 39-94) for anti-CCP1 and anti-CCP2, respectively; mean (SD) specificity was 96 (3)% (range 90-99) and 95 (5)% (range 81-100) for anti-CCP1 and anti-CCP2, respectively. Predictive properties were assessed in 14 studies; odds ratio (95% confidence interval) of anti-CCP1 and anti-CCP2 for the future development of RA were 20 (14 to 31) and 25 (18 to 35), respectively, among patients with early undifferentiated arthritis and 64.5 (8.5 to 489) and 28 (8 to 95), respectively, among healthy subjects. Conclusion: Sensitivity of the second generation of anti-CCP is close to that of rheumatoid factor, with a higher specificity, for distinguishing RA from other rheumatic diseases. Moreover, anti-CCP antibodies appear to be highly predictive of the future development of RA in both healthy subjects and patients with undifferentiated arthritis.

Comparison of Rheumatoid Factor (RF) and Anti Cyclic Citrullinated Peptide (Anti -CCP) Antibodies in Early Diagnosis of Rheumatoid Arthritis

INDIAN JOURNAL OF APPLIED RESEARCH, 2020

Background: Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammation of joints causing deformities and functional impairment. Rheumatoid factor (RF) is an autoantibody specific for the Fc portion of human IgG. RF has low specificity as high false positive results are common in the general population. Anti CCP (Anti-cyclic citrullinated peptide) antibody is also a useful marker to diagnose rheumatoid arthritis and included in one of the criteria of the American College of Rheumatology (ACR) /European League against Rheumatism (EULAR) classification of RA. This study is done to compare the diagnostic utility of Anti CCP and RF test in RA patients. Aim & Objective: Comparison of rheumatoid factor (RF) and Anti cyclic citrullinated peptide (Anti -CCP) antibodies in diagnosis of rheumatoid arthritis- in a tertiary care hospital. Material &Methods: A total of 70 samples were taken from clinically suspected RA patients over a period of 6 months.RF and AntiCCP...

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

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 northeastern 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 cutoff 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 NorthEastern part of India.

Anti-cyclic citrullinated peptide versus anti-Sa antibodies in diagnosis of rheumatoid arthritis in an outpatient clinic for connective tissue disease and spondyloarthritis

The Journal of rheumatology, 2006

To compare the diagnostic value of anti-cyclic citrullinated peptide (anti-CCP) and anti-Sa antibodies in serum for prediction of rheumatoid arthritis (RA) in an outpatient clinic for connective tissue diseases and spondyloarthritides. Methods. A cross-sectional study was carried out to analyze the presence or absence of anti-CCP and anti-Sa antibodies in the sera of 250 randomly selected patients. The disease distribution in the study was as follows: 87 patients had RA (34.8%); 90 (36%) had other connective tissue diseases (CTD); 50 (20%) spondyloarthritis; 19 (7.6%) polymyalgia rheumatica; and 4 (1.6%) juvenile idiopathic arthritis. Results. Anti-CCP antibodies were detected in 63 patients with RA and in 9 patients with other illnesses [sensitivity 72.4%, specificity 94.4%, positive predictive value (PPV) 87.5%]. Anti-Sa antibodies were detected in 38 patients with RA and in 6 patients with other illnesses (sensitivity 43.6%, specificity 96.3%, PPV 86.3%). Anti-CCP and anti-Sa results were discordant in up to 47 of 87 RA patients. No relation between the presence of anti-Sa and higher or lower titers of anti-CCP antibodies was observed. Conclusion. The diagnostic value in RA is similar for both antibodies. However, the sensitivity of anti-CCP detection is higher than that of anti-Sa. Our results suggest that presence of anti-Sa antibodies in serum may be useful as a complementary assay when anti-CCP antibodies are negative and RA is suspected.