Serum Levels Of anti-CCP Antibodies Research Articles

Frequency of Positive Anti-CCP Antibodies in Rheumatoid Arthritis Patients with Negative Rheumatoid Factor

Background: Rheumatoid arthritis (RA) is a polyarticular autoimmune disease that affects about 1% of the adult population. The disease is characterized by synoviocyte hyperplasia, mainly synovial fibroblasts, resulting in bone and joint destruction. Recent studies have shown that cytokines and other systemic inflammation mediators have a key role in the development ofrheumatoid arthritis. Recently, Anti-Citrullinated Protein Antibodies (anti-CCP) have come into use for the diagnosis of rheumatoid arthritis (RA). It has been reported that anti-CCP has quite a high specificity for RA (98%), together with sensitivity similar to that for rheumatoid factor (RF). The study aimed to determine the frequency of positive anti-CCP antibodies in rheumatoid arthritis patients with negative rheumatoid factor.
 Methods: 91 patients (both male and females) aged 40-70years with negative RF were clinically diagnosed with rheumatoid arthritis. Patients with positive rheumatoid factor and joint injuries were disclaimed. The consultant pathologist used a second-generation enzyme-linked immunosorbent assay (ELISA) to assess the serum levels of anti-CCP antibodies, >20IU/ ml is considered positive p-value of 0.05 were considered statistically significant.
 Results: In the study, the age range was 40 to 70 years, averaging 53.44 ± 7.16 years. 59 (64.84%) of the patients were between the ages of 40 and 55. Of 91 patients, 56 (61.54%) were women, and 35 (38.46%) were men with aratio of 1.6:1 man to women. In patients with negative rheumatoid factors, 27 (40.66%) patients were found to have the levels of positive anti-CCP antibodies.
 Conclusion: Patients with negative rheumatoid factor showed the high frequency of positive anti-CCP.

Association of anti-cyclic citrullinated peptide antibodies and rheumatoid factor isotypes with HLA-DRB1 shared epitope alleles in Egyptian rheumatoid arthritis patients.

The most common genetic risk factor for rheumatoid arthritis (RA) is human leucocyte antigen DRB1 (HLA-DRB1) shared epitope (SE). To investigate the relationship between anti-cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), immunoglobulin (Ig)G, IgM and IgA and HLA-DRB1 SE among Egyptian patients with RA. Serum levels of anti-CCP antibodies and RFIgG, RFIgM, RFIgA were assayed using enzyme-linked immunosorbent assay for 157 Egyptian RA patients and 150 healthy controls attending the outpatient clinics of National Research Center and Kasr El Aini Hospital. HLA-DRB1 genotyping was performed by the DynalAllSetTM polymerase chain reaction (PCR) single specific primer low-resolution typing kits. Amplified PCR product was checked using 3% agarose gel. HLA-DRB1-SE was found among 129 (82.2%) RA patients and 67 (44.7%) controls (odds ratio [OR] 5.7, CI 3.4-9.6, P<.0001). The risk of RA development was higher with the presence of SE two alleles (OR 11.6, P<.0001), while the OR for 1 copy SE allele was 4.4 (P<.0001). HLA-DRB1-SE was significantly associated with positive as well as negative anti-CCP and RF isotypes. The stronger association was with anti-CCP positivity with OR 11 (5.1-23.6), P<.0001. Furthermore, the risk of development of positive anti-CCP and RF isotypes was higher with the presence of 2 copies of SE alleles than with 1 copy. The prevalence of HLA-DRB1-SE is high in Egyptian RA patients. The role of SE in RA patients is most probably related to the development of anti-CCP positive RA rather than the development of anti-CCP positivity.

Chronic administration of Cl-amidine, a pan-peptidylarginine deiminase inhibitor, does not reverse bone loss in two different murine models of osteoporosis.

Recent in vitro studies have shown a role for the peptidyl-arginine deiminases (PADs) in bone resorption. However, it is unknown whether these enzymes are involved in bone loss in vivo. Thus, we evaluated the antiresorptive effect of a pan-PAD inhibitor in two murine models of osteoporosis: (a) primary osteoporosis induced by ovariectomy (OVX); and (b) secondary osteoporosis associated to Type-1 diabetes induced by streptozotocin (STZ, 50 mg/kg, i.p., five daily administrations). Five weeks after OVX and 15 weeks after injections of STZ, mice received daily administrations of Cl-amidine (3 or 10 mg/kg, i.p.) or vehicle for 30 consecutive days. At the end of the treatment, femur and vertebra were harvested for microCT analysis. Blood samples were collected for determination of antibodies against cyclic citrullinated peptides (anti-CCP) by enzyme-linked immunosorbent assay. Serum levels of anti-CCP antibodies from diabetic mice were not significantly different compared to control mice. However, a significant loss of both trabecular bone at the femoral neck and cortical bone at the femoral diaphysis was found in diabetic mice, and Cl-amidine did not reverse the diabetes-induced bone loss. Mice with OVX had significantly lower serum levels of anti-CCP compared to mice with sham surgery. OVX resulted in significant loss of both trabecular bone at the L5 vertebra and distal femoral metaphysis. Cl-amidine did not block the OVX-induced bone loss. Our results suggest that chronic treatment with Cl-amidine at the doses and period of time administered is not long enough to inhibit bone loss in two different murine models of osteoporosis.

Interactions between smoking, increased serum levels of anti-CCP antibodies, rheumatoid factors, and erosive joint disease in patients with early, untreated rheumatoid arthritis

Objectives: To determine to what extent shared epitopes, smoking, and anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with disease activity and erosive disease in patients with rheumatoid arthritis (RA) at disease onset.Method: RA patients not previously treated with disease-modifying anti-rheumatic drugs (DMARDs) and with a disease duration of < 6 months (CIMESTRA study) were examined for shared epitopes, anti-CCP antibodies, immunoglobulin M rheumatoid factor (IgM-RF) and IgA-RF, radiographic erosive changes in hands and feet, and clinical disease activity.Results: The study comprised 153 patients, of whom 104 (68%) were ever-smokers. The prevalence of patients with 0, 1, or 2 shared epitopes was 40 (48%), 71 (49%), and 33 (23%), respectively. Anti-CCP antibodies, IgM-RF, and IgA-RF were present in 89 (58%), 99 (65%), and 82 (54%) patients, respectively. Among smokers, erosive disease was associated with anti-CCP antibodies [odds ratio (OR) 3.9, 95% confidence interval (CI) 1.6–9.3], IgM-RF (OR 4.9, 95% CI 1.9–12), and IgA-RF (OR 2.8, 95% CI 1.2–6.4) but absent with regard to shared epitopes. Among never-smokers, erosive disease was not associated with either shared epitopes or antibodies. All antibody levels measured were associated with smoking and shared epitopes.Conclusions: Shared epitopes and smoking were associated with the production of anti-CCP antibodies and rheumatoid factors of IgM and IgA isotypes, which again were associated with erosive disease at presentation only in smokers. As shared epitopes and smoking were not directly associated with erosive disease, smoking may enhance the development of erosive disease in RA at different levels or through separate pathways.

AB0356 Advantageous Effect of Small Doses of Atorvastatin on A Chemokines Profile and Clinical Activity of Rheumatoid Arthritis

BackgroundIn patients with rheumatoid arthritis (RA) treated with statins it is difficult to establish their pleiotropic, including anti-inflammatory, effect due to the high activity of the inflammatory process in the...

SAT0059 Association of Serum Antibody Responses to Porphyromonas Gingivalis and Periodontal Conditions with Clinical Response to Biologics in Rheumatoid Arthritis Patients

BackgroundThere is little evidence on prediction of clinical response to biologics in patients with RA. Recently, it has been suggested that clinical response to tumor necrosis factor (TNF) inhibitors was...

AB0276 Methotrexate therapy monitoring by MTOR, autophagy-related ULK1, caspase 3, CDK-inhibitor p21, TNF alpha, and osteoclast-specific cathepsin K and gelatinase MMP-9 gene expression in the peripheral blood of early rheumatoid arthritis patients

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia, mononuclear cell infiltration, bone erosion and joint destruction. Altered rates of cell proliferation and apoptosis were also observed...

AB0529 Rituximab therapy monitoring by mtor, autophagy-related ULK1, caspase 3, CDK-inhibitor P21, TNF alpha, and osteoclast-specific cathepsin K and gelatinase MMP-9 gene expression in the peripheral blood of rheumatoid arthritis patients

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia, mononuclear cell infiltration, bone erosion and joint destruction. Altered rates of cell proliferation and apoptosis were also observed...

Clinical immunology Effect of methotrexate on serum levels of anti-CCP antibodies and different classes of rheumatoid factors in rheumatoid arthritis patients

Clinical immunology Effect of methotrexate on serum levels of anti-CCP antibodies and different classes of rheumatoid factors in rheumatoid arthritis patients

Detection of autoantibodies to citrullinated BiP in rheumatoid arthritis patients and pro-inflammatory role of citrullinated BiP in collagen-induced arthritis

IntroductionAnti-citrullinated protein/peptide antibodies (ACPAs) are highly specific to rheumatoid arthritis (RA) patients and are thought to have a close relationship with the pathogenesis of arthritis. Several proteins, including fibrinogen, vimentin, and alpha-enolase, were reported as ACPA-target antigens, and their importance in RA pathogenesis was widely proposed. We identified citrullinated immunoglobulin binding protein (citBiP) as another ACPA target in RA patients and examined its pro-inflammatory role in arthritis.MethodsWe measured the levels of anti-citBiP, anti-BiP, and anti-cyclic citrullinated peptide (CCP) antibodies in the serum of RA patients (n = 100), systemic lupus erythematosus (SLE) patients (n = 60), and healthy controls (n = 30) using ELISA and immunoblotting. Epitope mapping was performed using 27 citBiP-derived peptides. In the mouse study, after DBA/1J mice were immunized with BiP or citBiP, serum titers of ACPAs were measured by ELISA and immunohistochemistry. The development of collagen-induced arthritis (CIA) was observed in BiP- or citBiP-pre-immunized mice.ResultsThe serum levels of anti-BiP and anti-citBiP antibodies were significantly increased in RA patients, although only anti-BiP antibodies were slightly increased in SLE patients. Interestingly, anti-citBiP antibody levels were higher than anti-BiP antibody levels in 72% of RA patients, whereas no significant increase in anti-citBiP antibody levels was detected in SLE patients and healthy controls. The serum levels of anti-CCP antibodies were correlated with those of anti-citBiP antibodies in RA patients (R2 = 0.41). Several citrulline residues of citBiP were determined to be major epitopes of anti-citBiP antibodies, one of which showed cross-reactivity with CCP. Immunization of DBA/1J mice with citBiP induced several kinds of ACPAs, including anti-CCP and anti-citrullinated fibrinogen antibodies. Pre-immunization with citBiP exacerbated CIA, and anti-CCP antibody levels were increased in citBiP-pre-immunized CIA mice.ConclusionsCitBiP is a newly described ACPA target that may play a pro-inflammatory role in arthritis.

Serum levels of anti-CCP antibodies, anti-MCV antibodies and RF IgA in the follow-up of patients with rheumatoid arthritis treated with rituximab

Rheumatoid arthritis (RA) is characterized by the presence of circulating rheumatoid factor (RF) and anticitrullinated peptide antibodies (ACPA), which are positive in about 70–80% of patients. APCA have a higher specificity and therefore a higher diagnostic power than RF, but are less informative than RF in monitoring the course of the disease in patients under treatment. Recently, it has been reported that the anticitrullinated vimentin (a-MCV) antibody test can identify a particular subgroup of APCA that may be negative for anticyclic citrullinated peptide (a-CCP) antibodies. Concerning RF, the RF IgA isotype has been described as a more specific marker of erosive joint damage than total RF. The aim of our study was to monitor the levels of a-CCP, a-MCV, total RF and RF IgA in the follow-up of patients with RA treated with B-lymphocytedepletive rituximab (RTX), to detect any differences or peculiarities in patterns of these autoantibodies, especially in relation to their potential use as predictive markers of therapeutic response. We studied 30 patients with RA treated with RTX. All patients were previously unresponsive to at least 6 months of therapy with disease-modifying antirheumatic drugs (DMARDs; methotrexate, leflunomide, cyclosporine, chloroquine) and/or at least 6 months of therapy with anti-TNF biologics. The evaluation of response to RTX was made at month +6 using the EULAR criteria (DAS28). a-CCP, a-MCV, total RF and RF IgA were determined at baseline (before the first infusion of RTX) and after 1, 3 and 6 months. In serum samples obtained before treatment two cytokines essential for Blymphocyte proliferation, interleukin 6 (IL-6) and B-lymphocyte stimulator (BLyS) were also determined. In all patients a significant and consistent reduction in all the tested antibodies was found during follow-up, with no differences in respect of the degree of response to RTX. Of note, at baseline, generally a higher titre of all autoantibodies was seen in patients who then showed a better response to RTX. Finally, there were no differences in serum concentrations of IL-6 and BLyS in patients in relation to the presence or absence of the autoantibodies investigated, nor was there any significant correlation between the serum concentrations of the cytokines and the titres of the autoantibodies. Thus, neither a-MCV compared to a- CCP, nor RF IgA compared to routine total RF, provided any additional predictive information in the follow-up of patients with RA treated with RTX.

Predicting the Progression of Palindromic Rheumatism to Rheumatoid Arthritis: The Role of Ultrasonography and Anti-cyclic Citrullinated Peptide Antibodies

We investigated whether sonography and anti-cyclic citrullinated peptide (anti-CCP) antibodies in Chinese patients with palindromic rheumatism (PR) during active episodes are of predictive value for development of rheumatoid arthritis (RA). Clinically involved regions of 84 PR patients during active episodes were examined with ultrasonography using a 6–13 MHz linear transducer. Serum levels of anti-CCP antibodies were determined by enzyme-linked immunosorbent assay. All patients were followed up monthly for 3 years after investigation. Thirteen (15%) of the PR patients had progressed to RA after a mean of 1.4 years (range, 0.4–3.0 years). Of these 13 patients, 11 patients (85%) had sonographic features of synovitis and 8 patients (62%) had a positive anti-CCP antibody test. The absence of sonographic features of synovitis during active episodes provided a very high 3-year predictive value in excluding the possibility of progression to RA for PR patients with a negative anti-CCP antibody test. Both the sonographic findings of synovitis and a positive anti-CCP antibody test were significant predictors for progression of PR to RA within 3 years by backward stepwise logistic regression analysis. Sonographic examination together with an anti-CCP antibody test during active episodes is useful for predicting the progression of PR to RA.

Association of Ultrasonographic Findings of Synovitis With Anti-Cyclic Citrullinated Peptide Antibodies and Rheumatoid Factor in Patients With Palindromic Rheumatism During Active Episodes

The purpose of this study was to investigate whether the presence of ultrasonographic findings of synovitis is associated with the presence of anti-cyclic citrullinated peptide (CCP) antibodies and rheumatoid factor (RF) in patients with palindromic rheumatism (PR) during active episodes. Clinically involved regions of 84 patients with PR during active episodes were examined with high-resolution ultrasonography. Serum levels of anti-CCP antibodies were determined by an enzyme-linked immunosorbent assay, and RF levels were measured by nephelometry. Thirty patients (36%) had ultrasonographic findings of synovitis during active episodes. Significantly higher positive rates of anti-CCP antibodies and RF were observed in patients with PR who had ultrasonographic findings of synovitis compared with those who had no ultrasonographic findings of synovitis (26.7% versus 5.6%; odds ratio, 6.18; P < .05; and 30.0% versus 5.6%; odds ratio, 7.29; P < .01, respectively). The intraobserver and interobserver agreement for the detection of synovitis and Doppler signals by ultrasonographic assessment was excellent. Ultrasonography is a reliable method for assessing the presence of synovitis in patients with PR during active episodes. The ultrasonographic findings of synovitis are associated with the presence of anti-CCP antibodies and RF in patients with PR.

The diagnostic value of anti-cyclic citrullinated peptide antibodies and rheumatoid factor in patients with rheumatoid arthritis

Objective: To identify the diagnostic value of anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF) in patients with rheumatoid arthritis (RA). Methods: Serum levels of anti-CCP antibodies were determined by enzyme-linked immunosorbent assay, and levels of RF were determined by nephelometry in 145 patients with RA and 75 patients with non-RA rheumatic diseases. Results: Among the 145 patients with RA, 119 patients (82.1%) tested positive for anti-CCP antibodies, and 116 patients (80.0%) tested positive for RF. The sensitivity, specificity, positive predictive value, and negative predictive value of anti-CCP antibodies for diagnosing RA were 82.1%, 88.0%, 93.0%, and 71.7% respectively. Those for RF were 80.0%, 62.7%, 81.1%, and 61.0% respectively. The presence of either anti-CCP antibodies or RF increased sensitivity to 88.3%, and when they both were present, the specificity increased to 94.7%. The positive rates for anti-CCP antibodies in the RF-positive RA, RFnegative RA, and non-RA patients were 93.1%, 37.9%, and 12.0% respectively. Conclusion: With its high sensitivity and specificity, the anti-CCP antibodies assay is a useful test for diagnosing RA. The use of anti-CCP antibodies and RF in combination further increases the diagnostic value for RA.