Anti–Cyclic Citrullinated Peptide Antibodies in the Diagnosis of Rheumatoid Arthritis: Bayes Clears the Haze (original) (raw)
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Anti-Cyclic Citrullinated Peptide Antibodies in Patients with Juvenile Idiopathic Arthritis
Immunological Investigations, 2008
Rheumatoid arthritis (RA) is associated with progressive joint destruction and disability. Early diagnosis of RA is important, since early and aggressive treatments lead to a better outcome. Circulating autoantibodies are a serological hallmark of systemic rheumatic diseases. More recently, antibodies directed to a cyclic citrullinated peptide, anti-CCP antibodies, have been established as specifi c diagnostic and prognostic tools for RA. The aims of this study were to assess the diagnostic and radiological prognostic value of the anti-CCP antibody in Turkish patients with RA (n = 97) and those with Behçet's disease (BD) (n = 46). The study also included 35 healthy controls. Anti-CCP antibodies were measured by ELISA, and radiological damage was evaluated by using modifi ed Larsen scoring. In the RA group, sensitivity and specifi city were 80.4% and 93.5% for rheumatoid factor (RF), and 74.2% and 97.8% for anti-CCP antibody, respectively. RF was positive in 3 BD patients (6.5%) and in one of the controls (2.9%). In contrast, anti-CCP antibodies were detected in one BD patient (2.2%), but not in the control subjects. Deformed joint counts and radiographic scores were higher in anti-CCP antibody-positive RA patients (n = 72) than those in anti-CCP antibody-negative patients (n = 25) (p < 0.05). Moreover, anti-CCP antibody titer correlated with deformed joint count (r = 0.224, p < 0.05) and radiographic score (r = 0.308, p < 0.05). This study indicates the diagnostic and prognostic utility of anti-CCP antibodies in Turkish patients with RA. Importantly, anti-CCP antibodies are not associated with BD. Rheumatoid arthritis; Behçet's disease; anti-cyclic citrullinated peptide antibody; radiological progression
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.
Indonesian Journal of Rheumatology, 2018
Background. The second generation anti-cyclic citrullinated peptide test (CCP2) displays sensitivity comparable to that of rheumatoid factor (RF) (approximately 80%) but with superior specificity (98%) . Several observations have indicated that early rheumatoid arthritis (RA) patients with positive anti-CCP may develop a more erosive disease than those without anti-CCP. Objective. The purpose of this cross-sectional study was to investigate the correlation between anti-CCP antibodies and clinical and laboratory parameters and radiological joint destruction in RA patients. Methods. We studied 31 patients with RA fulfilling the 1987 revised criteria of American College of Rheumatology in Rheumatology Clinic of Saiful Anwar General Hospital, Malang, Indonesia. Clinical parameters were collected such as age, sex, visual analog scale, disease duration and diseases activity score (DAS28-3(CRP)). Laboratory parameters were WBC, hemoglobin, platelet count, erythrocyte sedimentation rate, an...
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).
Predictive value of antibodies to cyclic citrullinated peptide in patients with early arthritis
Clinical Rheumatology, 2006
The objective of this study was to determine the diagnostic value for rheumatoid arthritis (RA) of antibodies to cyclic citrullinated peptides (anti-CCP) in patients with early arthritis and vasculitis. Sixty-four adult patients with early arthritis and disease duration of less than 4 months were clinically diagnosed by an experienced rheumatologist as having RA (n=27), spondyloarthropathy (n=11), and undifferentiated arthritis (n=26). Eighteen patients with vasculitis were also included in the study. The patients with early arthritis were followed up for 9 months. After the follow-up period, five of 26 patients with undifferentiated arthritis were diagnosed as having RA. All serum samples were tested for anti-CCP and IgM rheumatoid factor (IgM-RF). The anti-CCP positivity in RA patients (44.4%) was significantly more frequent than in patients with undifferentiated arthritis (3.8%), spondyloarthropathy (0%), and vasculitis (5.6%) (p=0.001, p<0.01, and p<0.01, respectively). The frequency of IgM-RF positivity was 40.7% in RA, 7.7% in undifferentiated arthritis, 0% in spondyloarthropathy, and 22.2% in vasculitis groups. The respective specificity of anti-CCP and IgM-RF tests for early RA were 97.3 and 94.6%, and the respective sensitivity of them were 44.4 and 40.7%, respectively. The combination of anti-CCP and IgM-RF positivity had a very high specificity and positive predictive value (100%) but a rather low sensitivity (33.3%). When either anti-CCP or IgM-RF positivity combined into one criterion, the sensitivity became high (51.9%) but the specificity decreased to 91.9%. Overall performance of anti-CCP test alone for the early RA was higher than IgM-RF and the combination of anti-CCP and IgM-RF (p<0.05), and was similar to the combination of anti-CCP or IgM-RF. The specificity of positive anti-CCP test for diagnosis of established RA reached up to 100%. In conclusion, the anti-CCP test is a new diagnostic test with extremely high specificity for RA. Anti-CCP antibody testing combined with IgM-RF testing has additional value over IgM-RF testing alone in patients with early arthritis.
"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.
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.
Diagnostic performances of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis
Rheumatology International, 2007
To evaluate the rheumatoid arthritis (RA) diagnostic performances of anti-cyclic citrullinated peptide antibodies (anti-CCP). Anti-CCP was detected by an enzyme linked immunosorbent assay in 164 patients with RA and 343 controls. In addition, anti-CCP predictive value for radiological damage were investigated in 37 recent-onset RA patients followed up prospectively for 2 years. Radiological damages were assessed by Sharp method modified by van der Heijde. The sensitivity of anti-CCP was 78.7% and the specificity was 95.6%. The positive predictive value and the negative predictive value were 90.2% and 90.3%, respectively. Anti-CCP were detected in sera of 79.3% of patients with recent onset RA and 78.3% of patients with long disease duration. In univariate and multivariate analyses, anti-CCP were not predictive for radiological damage. Our study confirms the high diagnostic performances of anti-CCP in RA. They are very useful to aid the diagnostic of RA in clinical practice.