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The Diagnostic Value of Anti-Cyclic Citrullinated Peptide Antibodies (anti-CCP) in Patients with Rheumatoid Arthritis

A cross-sectional study was carried out to analyze the prevalence of anti-CCP antibodies and IgM RF in the sera of 160 randomly selected patients from the Rheumatology Department: 60 with RA, 50 with other rheumatic diseases (non-RA), 50 healthy controls (HC). The mean age of the group was 50.06+/-11.9 years. There were 141 females (88.1%) and 19 males (11.9%). RA patients fulfilled the revised ACR criteria. The mean duration of the disease was 82.4 months. Anti-CCP ELISA kit and IgM RF Latex test were used. The mean anti-CCP values were as follows: RA 60.4+/-57.6, non-RA 2.1+/-3.6, HC 1.3 +/-0.4 U/mL. Respectively, the mean values of IgM RF were: RA 515.8+/-525, non-RA 102+/-294, HC 15+/-57.5. Forty out of 60 (66.6%) RA patients were anti-CCP positive. Forty one out of 60 (68.3%) RA patients were positive for IgM RF. As expected, anti-CCP showed comparable sensitivity (66.8% vs. 68.3%) and higher specificity (98% vs. 87%) than IgM RF, at optimal cut-off values. The presence of either anti-CCP or IgM RF increased the testing sensitivity for the diagnosis of RA to 76.6%. AUC was greater for anti-CCP than for IgM RF (0.92 vs. 0.82).

-Oleas, Servicio de Inmunologı́a, Edificio de Laboratorios, 3a planta, Hospital Universitario Virgen del Rocı́o, Avenida Manuel Siurot s/n, 41013, Sevilla, Spain Phone: q34-955013231, Fax: q34-955013221, E-mail: Keywords: anti-cyclic citrullinated peptide antibodies (anti-CCP); rheumatoid arthritis; rheumatoid factor; third-generation anti-CCP ELISA. Introduction Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of peripheral joints, leading to severe destruction. This disease affects between 0.5% and 1% of

antibodies for very early rheumatoid arthritis. J Rheumatol 2006; 33 (12): 2390-7. Damjanovska V, Atanasovska V, Gruev T. The diagnostic value of anti-cyclic citrullinated peptide antibodies (anti-CCP) in patients with rheumatoid arthritis. Journal of Medical Biochemistry 2007; 26 (4): 285-288. Spasovski D, Gruev T, Marina N, Calovski J, Perčinkova S, Rajčevska Lj Osmani B, Cakalaroski K. The diagnostic value of the second generation anti-CCP test in rheumatoid arthritis. Journal of Medical Biochemistry 2008; 27 (1): 52-58. Spasovski D, Gruev T, Marina N, Calovski J


Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation and destruction of joint cartilage and bone. Different cytokines play important role in the processes that cause articular destruction and extra-articular manifestations in RA. The contribution of cytokines representing the Th1 (INF-γ), Th2 (IL-4) and IL-17A to the pathogenesis of early RA and bone mineral density (BMD) loss in still poorly understood. Serum samples of 38 early RA patients were evaluated for erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibodies (anti-CCP) and for the tested cytokines (IL-17A, IL-4 and INF-γ). BMD was evaluated by dualenergyX-ray absorptiometry (DXA). Disease activity score (DAS28) calculation was assessed for all patients. Control serum samples were obtained from 34 healthy volunteers. The levels of tested cytokines were significantly higher (IL-17A, p<0.001; INF-γ, P<0.001; IL-4, P<0.01) in patients with early RA, compared to the healthy controls. In early RA patients, strong correlation of serum IL-17A was found with DAS28, ESR and CRP. Also, a significant negative correlation was found between serum INF-γ levels and the DAS28 score. Significantly positive correlation of BMD values and CRP, DAS28 IL-17A were also demonstrated. DXA analysis revealed that the most common site for osteoporosis was the lumbar spine followed by the femoral neck. BMD values significantly correlated with CRP, DAS28 score and IL-17A serum levels. The mean serum IL-17A levels, in patients with early RA, corresponded with disease activity, severity and BMD loss, indicating the potential usefulness of serum IL-17A in defining the disease activity and bone remodeling.

(CRP), anti-cyclic citrullinated peptide antibody (anti- CCP), rheumatoid factor (RF) and TNFα, as posible factors implicated in the pathogenesis of RA. Methods. We investigated sera from 60 RA and 20 healthy control, during 3 years, for anti-CCP(second and third generation), FR and TNFα using ELISA-INOVA kit and for CRP by Mancini technique. Results. Anti-CCP antibodies were found to be positive in 60% of cases and FR at 75% of patients. We have found that serum anti-CCP and IgA RF are present for a median of 2-3 years prior to the onset of symptoms in patients who

were renewed in order to detect the disease earlier [4]. In the newest criteria set serological findings were weighted. About 60%–70% of the patients with RA have elevated levels of either rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibodies (anti-CCP), or both [5, 6]. IgG antibodies directed towards a synthetic citrullinated type II collagen peptide were detectable in 40% of the cases in a cohort of early RA patients. These autoantibodies are specifically bound to the citrullinated triple helical collagen type II amino acid residues 359–369 [7

were based on combinations of the following index terms: rheumatoid arthritis; CCP; anti-CCP antibodies; anti-CCP antibody; anti-cyclic citrullinated peptide antibodies and anti-cyclic citrullinated peptide antibody; second-generation assays of anti-cyclic citrullinated peptide antibodies; anti-CCP-2 and anti-CCP3; and CCP-2 and CCP-3. We also reviewed the reference lists of retrieved studies and review articles. Study selection Two reviewers independently scanned abstracts that met the inclusion criteria. We included studies that evaluated the utility of assaying

peptide antibodies (anti-CCP) are a serological marker of rheumatoid arthritis and also have a prognostic value for more aggressive disease. This study aimed to investigate vitamin D status on anti-CCP and rheumatoid factor serum levels in RA patients. Methods Cross-sectional study. January, February and March were considered winter, April, May and June, were evaluated as spring, summer months were July, August and September and finally, autumn included October, November and December. Anti- CCP over 60 U/mL and rheumatoid factor (RF) above 15 IU/mL were considered

24 % with breast tumor. Patients were examined for the presence of autoantibodies: rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP) test was performed by enzyme-linked immunosorbent assay (ELISA); anti-nuclear antibodies (ANA) were tested by indirect immunofluorescence on Hep-2 cells; immunoblotting technique was used to detect autoantibodies to anti-neuronal antibodies (ANNA). RESULTS RF was detected in 31% of patients with paraneoplastic rheumatic syndrome and in 20% of control group; it should be noted that 45% of patients with

) depending on anti-cyclic citrullinated peptide antibody (anti-CCP) status may be helpful in distinguishing different aetiopathologies and in predicting course of disease (1). HLA-DRB1 shared epitope and peptidylarginine deiminase type 4 (PADI4) genotype, which have been implicated in anti-CCP generation and protein citrullination, respectively, are assumed to be associated with susceptibility to RA (2). Aims: To elucidate whether PADI4 affects clinical characteristics of RA, and whether it modulates the effect of anti-CCP on clinical course. Methods: In 373 RA