anti-CCP Antibody Levels Research Articles

Baseline serum adipokine levels predict radiographic progression in early rheumatoid arthritis

Adipose tissue can secrete soluble mediators (adipokines) with potent immune regulatory functions. Some adipokines have been previously associated with radiographic damage in patients with rheumatoid arthritis (RA). In the present study, we investigated the capacity of baseline adipokine levels to predict radiographic progression over a period of 4 years and studied their contribution relative to that of other known risk factors, such as anti-cyclic citrullinated peptide (anti-CCP) antibodies. Serum concentrations of leptin, visfatin, resistin, adiponectin, adipsin, tumor necrosis factor α (TNFα), and interleukin-6 (IL-6) were determined in serum samples obtained at baseline from 253 patients with RA from the Early Arthritis Cohort. The association between levels of these adipokines and radiographic progression was determined using a multivariate normal regression model correcting for age, sex, treatment strategy, body mass index (BMI), and the presence of anti-CCP antibodies. Levels of IL-6, TNFα, visfatin, and adiponectin were positively associated with radiographic progression over 4 years. This association was independent of BMI. However, only adiponectin levels remained significantly associated with radiographic progression when the model was corrected for the presence of anti-CCP antibodies, whereas a trend was observed for IL-6. The association of both TNFα and visfatin with radiographic damage disappeared after correction for the presence of anti-CCP antibodies, which is consistent with the fact that the levels of both cytokines correlated significantly with anti-CCP antibody levels in these patients. Our results indicate that adipokines are predictors of radiographic progression in RA, possibly through distinct underlying biologic mechanisms.

Diagnostic value of serum and joint fluid anti-CCP (citrulline-containing peptide) antibody for rheumatoid arthritis and its relationship with other inflammatory indicators

To investigate the diagnostic sensitivity and specificity of serum and joint fluid citrulline-containing peptide (CCP), variant antibody (anti-CCP antibody) for active rheumatoid arthritis (RA) and to explore their relationship with other clinical inflammatory indicators, the levels of serum and joint fluid anti-CCP antibodies, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and rheumatoid factors (RF) were detected in 104 active RA patients including 68 with knee joint effusion. The sensitivity of serum anti-CCP antibody to RA was 92.3% (96/104) and that of joint fluid anti-CCP antibody was 82.4% (56/68) (P>0.05). The specificity of serum and joint fluid anti-CCP antibody was 100%. There was no significant correlation between anti-CCP antibody and ESR, CRP, score of DAS28, and RF in RA patients positive for serum anti-CCP antibody (P>0.05). After treatment for half month with integrated traditional Chinese and Western medicine, all indicators were improved. The levels of ESR, CRP, RF, score of DAS28 and serum anti-CCP antibody were decreased significantly after treatment when compared with those before treatment (P<0.05). In our study, two patients with early RA (course<2 months) were negative for serum anti-CCP antibody but positive for joint fluid anti-CCP antibody, and seroconversion was noted with the prolongation of disease duration. Combination of serum anti-CCP antibody and joint fluid anti-CCP antibody is helpful for the “early diagnosis” of RA and evaluation of the severity of RA, thus providing basis for the early treatment. The negativity and positivity of anti-CCP antibody are interchangeable under certain conditions. Key words: Anti-CCP antibody, rheumatoid arthritis, early diagnosis.

Proteoglycan‐induced arthritis and recombinant human proteoglycan aggrecan G1 domain–induced arthritis in BALB/c mice resembling two subtypes of rheumatoid arthritis

To develop a simplified and relatively inexpensive version of cartilage proteoglycan-induced arthritis (PGIA), an autoimmunity model of rheumatoid arthritis (RA), and to evaluate the extent to which this new model replicates the disease parameters of PGIA and RA. Recombinant human G1 domain of human cartilage PG containing "arthritogenic" T cell epitopes was generated in a mammalian expression system and used for immunization of BALB/c mice. The development and progression of arthritis in recombinant human PG G1-immunized mice (designated recombinant human PG G1-induced arthritis [GIA]) was monitored, and disease parameters were compared with those in the parent PGIA model. GIA strongly resembled PGIA, although the clinical symptoms and immune responses in mice with GIA were more uniform than in those with PGIA. Mice with GIA showed evidence of stronger Th1 and Th17 polarization than those with PGIA, and anti-mouse PG autoantibodies were produced in different isotype ratios in the 2 models. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies were detected in both models; however, serum levels of IgG-RF and anti-CCP antibodies were different in GIA and PGIA, and both parameters correlated better with disease severity in GIA than in PGIA. GIA is a novel model of seropositive RA that exhibits all of the characteristics of PGIA. Although the clinical phenotypes are similar, GIA and PGIA are characterized by different autoantibody profiles, and the 2 models may represent 2 subtypes of seropositive RA, in which more than 1 type of autoantibody can be used to monitor disease severity and response to treatment.

Are the anti-cyclic citrullinated peptide antibodies independent predictors of myocardial involvement in patients with active rheumatoid arthritis?

The anti-CCP antibodies are specific serological markers of RA, especially the aggressive course of joint disease. It has been postulated that the chronic inflammatory state is underlain by cardiovascular (CV) disease and that a higher level of anti-CCP antibodies is implicated in CV risk. The aim of the study was to assess: (i) the possible impact of anti-CCP antibodies on left ventricular diastolic dysfunction; and (ii) the possible differences in the effects of DASs on diastolic dysfunction. The study included 80 RA patients (70 females and 10 males) with no clinically evident CV disease, or concomitant diseases, and 80 matched healthy controls. Upon clinical and laboratory evaluation, all subjects underwent M-mode, two-dimensional and colour Doppler echocardiographic examination. Isovolumetric relaxation time (IVRT) prolongation as the first sign of diastolic dysfunction was present in 36.25% of RA patients and in 15% of control subjects. IVRT was found to correlate with anti-CCP antibody titre (r = 0.382, P = 0.002) and modified DAS including CRP [DAS-28-CRP(4v)] (r = 0.204, P = 0.039). On multivariate linear regression analysis, anti-CCP antibody titre showed significant correlation with IVRT, while the ratio of early and late transmitral wave (E/A ratio) independently correlated with age and DAS-28-CRP(4v). Anti-CCP antibody is an important marker, independently associated with impaired left ventricular relaxation and the DAS-28-CRP(4v) is a more sensitive predictor of cardiac involvement in the RA than the DAS-28 variant including the ESR.

Associations of HLA-DRB1 alleles with anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in northern east part of Turkey

The aim of this study was to investigate the associations between human leukocyte antigen (HLA)-DRB1 alleles with genetic susceptibility to rheumatoid arthritis (RA) and production of antibodies against cyclic citrullinated peptide (anti-CCP antibody) and rheumatoid factor (RF) in Turkish RA patients. We studied 291 RA patients and 253 controls. Genotyping was performed by polymerase chain reaction with sequence-specific oligonucleotide probes hybridization method. Serum levels of anti-CCP antibody, IgM-RF and high sensitive C-reactive protein titers were measured by commercial kits using immunological methods. We found that HLA-DRB1*04 and *09 alleles were associated in anti-CCP+ and anti-CCP+ RA patients (P < 0.0001 and P < 0.001, respectively), while DRB1*01 and *04 were determined to be higher in RF+ RA patients (P < 0.001 and P < 0.0001, respectively). Moreover, DRB1*11 and DRB1*13 alleles were determined to be lower in RF and anti-CCP/RF+ RA patients (P < 0.001 for both). HLA-DRB1*04 was identified as a common responsible allele for susceptibility to the disease in anti-CCP, RF and anti-CCP/RF- RA patients (P = 0.0018, P = 0.0004 and P = 0.0023, respectively). HLA-DRB1*13 allele alone was found to be protective against to anti-CCP+ and RF- RA (P = 0.0003 and P = 0.006, respectively). On the contrary, there was no protective allele in anti-CCP/RF- RA as well as anti-CCP- RA patients. This study indicates that associate and protective HLA-DRB1 allele distributions are different in autoantibody (anti-CCP or RF or anti-CCP/RF)+ RA and autoantibody- RA patients, with exceptions of DRB1*04 and DRB1*13.

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.

Relationship between Anti-CCP Antibodies and Oxidant and Anti-Oxidant Activity in Patients with Rheumatoid Arthritis

A new group of autoantibodies in Rheumatoid Arthritis (RA), the anti-cyclic citrullinated peptide (anti-CCP) antibodies directed to citrulline-containing proteins, which are of value for the severity of RA. Up to date, the relationship between anti-CCP antibodies and oxidant, anti-oxidant activity in patients with RA has not been elucidated in the previous studies. In this study we aimed to investigate the effect of anti-CCP antibodies in the circulation on whole blood, serum and synovial fluid oxidant and anti-oxidant activity in patients with RA. RA patients with anti-CCP (+) (n=25) and anti-CCP (-) (n=24) were recruited into the study. All patients had a positive rheumatoid factor (RF). The patients who were under treatment with only non-steroidal antiinflammatory drugs (NSAID) at the study time included in the study. Catalase (CAT), Glutathione peroxidase (GSHPx), Myeloperoxidase (MPO) activities and the levels of Malondialdehyde (MDA) were measured in whole blood, serum and synovial fluid in both groups. There were no significant differences in terms of the mean whole blood and serum antioxidative activity (CAT, GSHpx) and the mean blood and serum MDA and MPO values (oxidative activity), between the patients with anti-CCP(+) and those with anti-CCP(-). There was increased synovial oxidant activity (MDA and MPO levels) (p<0.05) in anti-CCP(+) RA patients with or without ESR negativity when compared with anti-CCP(-) RA patients. There was positive correlation between anti-CCP antibody levels and synovial MDA and MPO levels (r=0.435, p<0.05, r=0.563, p<0.05 respectively) in anti-CCP (+) group. In conclusion, anti-CCP antibody positivity seems to be associated with increased synovial fluid oxidant activity (increased MDA and MPO levels) in patients with RA. These conclusions need to be validated in a larger controlled study population.

Association study of single nucleotide polymorphisms in pre-miRNA and rheumatoid arthritis in a Han Chinese population

The aim of this study was to perform an association study between two single nucleotide polymorphisms (SNPs) rs2910164 G>C and rs3746444 T>C in pre-miRNA (hsa-mir-146a and hsa-mir-499) and rheumatoid arthritis (RA) in the Han Chinese population. 208 Han Chinese patients with RA and 240 healthy controls were recruited in this study. The SNPs was genotyped by polymerase chain reaction-restriction fragment length polymorphism. Anti-cyclic citrullinated peptide (anti-CCP) antibody was measured by enzyme linked immunosorbent assay and rheumatoid factor (RF) was measured by rate nephelometry. The genotype frequencies between cases and controls were compared by χ(2) analysis. No significant association between the SNPs (rs2910164 and rs3746444) and RA was observed (P = 0.631 and 0.775, respectively), and the SNPs did not show any association with the RF-positive (P = 0.631 and 0.775, respectively). However, there was a significant difference on the level of anti-CCP antibody between different genotypes in rs3746444 (P = 0.007). The heterozygote CT had significantly higher level of anti-CCP antibody compared with homozygote CC and TT (P = 0.054 and 0.003, respectively). We first investigated the association between the SNPs (rs2910164 G>C and rs3746444 T>C) in the pre-miRNA (hsa-mir-146a and hsa-mir-499) and RA in a Han Chinese population. We did not find a significant association between the SNPs and the susceptibility to RA, while the SNP rs3746444 may affect anti-CCP antibody production.

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.

Rheumatoid arthritis and periodontal disease

The prevalence of periodontal disease has increased two-fold among patients with rheumatoid arthritis (RA) compared to the general population. This increased prevalence is unrelated to secondary Sjögren's syndrome but instead reflects shared pathogenic mechanisms, including an increased prevalence of the shared epitope HLA-DRB1-04; exacerbated T-cell responsiveness with high tissue levels of IL-17; exaggerated B-cell responses, with plasma cells being the predominant cell type found within gingival tissue affected with periodontitis and B cells being twice as numerous as T cells; RANK overexpression; and an increase in the ratio of RANK-L over osteoprotegerin with a high level of RANK-L expression on gingival B cells, most notably those capable of recognizing Porphyromonas gingivalis. Other factors conducive to periodontitis include smoking and infection with the Epstein-Barr virus or cytomegalovirus, which act by promoting the growth of organisms such as P. gingivalis, whose DNA is often found in synovial tissue from RA patients. P. gingivalis produces the enzyme peptidylarginine deiminase that induces citrullination of various autoantigens, and levels of anti-CCP antibodies are considerably higher in RA patients with than without periodontal disease, suggesting that periodontitis may contribute to the pathogenesis of RA. Further support for this hypothesis comes from evidence that other antigens involved in RA, such as HC-gp39, are also present in gingival tissue. TNFα antagonists slow alveolar resorption but may perpetuate infection of periodontal pockets. Therefore, rheumatology patients, including those taking biotherapies, are likely to benefit from increased referral to dental care (e.g., scaling, root planing and, if needed, dental surgery), particularly as periodontitis is also associated with an increased risk of premature atheroma.

Increased concentration of two different advanced glycation end-products detected by enzyme immunoassays with new monoclonal antibodies in sera of patients with rheumatoid arthritis

BackgroundLevels of pentosidine (representative of advanced glycation end-products) in sera of patients with rheumatoid arthritis are increased when compared with sera of other diagnoses or healthy controls. These levels have been reported to correlate with clinical indices of rheumatoid arthritis activity and with laboratory markers of inflammation. The purpose of this study was to find out if these findings pertain to other advanced glycation end-products.MethodsWe have developed two immunoassays based on new monoclonal antibodies to advanced glycation end-products. Antibody 103-E3 reacts with an unidentified antigen, formed in the reaction of proteins with ribose, while antibody 8-C1 responds to Nε-(carboxyethyl)lysine. We have used these monoclonal antibodies to measure levels of advanced glycation end-products in sera of patients with rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, and healthy controls. We calculated the correlations between advanced glycation end-product levels in rheumatoid arthritis sera and the Disease Activity Score 28 (DAS28), age, disease duration, CRP, anti-CCP, rheumatoid factor and treatment with corticosteroids, respectively.ResultsLevels of both glycation products were significantly higher in sera of patients with rheumatoid arthritis when compared with sera of patients with systemic lupus erythematosus, osteoarthritis, or the healthy controls. Neither the level of Nε-(carboxyethyl)lysine nor the level of the 103-E3 antigen in rheumatoid arthritis sera correlated with the DAS28-scored rheumatoid arthritis activity. The levels of both antigens in rheumatoid arthritis sera did not correlate with age, gender, corticosteroid treatment, or levels of CRP, anti-CCP antibodies, and rheumatoid factor in sera.ConclusionsWe report highly specific increases in the levels of two advanced glycation end-products in sera of patients with rheumatoid arthritis. This increase could be explained neither by rheumatoid arthritis activity nor by inflammation. We propose a working hypothesis that presumes the existence of a link between advanced glycation end-product formation and induction of autoimmunity.

Left ventricular structure and function in patients with rheumatoid arthritis, as assessed by cardiac magnetic resonance imaging

Heart failure is a major contributor to cardiovascular morbidity and mortality in patients with rheumatoid arthritis (RA), but little is known about myocardial structure and function in this population. This study was undertaken to assess the factors associated with progression to heart failure in patients with RA. With the use of cardiac magnetic resonance imaging, measures of myocardial structure and function were assessed in men and women with RA enrolled in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis study, a cohort study of subclinical cardiovascular disease in patients with RA, in comparison with non-RA control subjects from a cohort enrolled in the Baltimore Multi-Ethnic Study of Atherosclerosis. Measures of myocardial structure and function were compared between 75 patients with RA and 225 frequency-matched controls. After adjustment for confounders, the mean left ventricular mass was found to be 26 gm lower in patients with RA compared with controls (P < 0.001), an 18% difference. In addition, the mean left ventricular ejection fraction, cardiac output, and stroke volume were modestly lower in the RA group compared with controls. The mean left ventricular end systolic and end diastolic volumes did not differ between the groups. In patients with RA, higher levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies and current use of biologic agents, but not other measures of disease activity or severity, were associated with significantly lower adjusted mean values for the left ventricular mass, end diastolic volume, and stroke volume, but not with ejection fraction. The combined associations of anti-CCP antibody level and biologic agent use with myocardial measures were additive, without evidence of interaction. These findings suggest that the progression to heart failure in RA may occur through reduced myocardial mass rather than hypertrophy. Both modifiable and nonmodifiable factors may contribute to lower levels of left ventricular mass and volume.

Anti-cyclic citrullinated peptide antibodies are not associated with familial Mediterranean fever

This study investigated the presence of anti-cyclic citrullinated peptide (anti-CCP) antibodies in familial Mediterranean fever (FMF) patients and controls. Forty-nine patients with FMF were enrolled (23 had a history of arthritis during attacks and 26 had no such history). Two control groups were enrolled: 20 patients with rheumatoid arthritis (RA) and 30 healthy individuals. Clinical and laboratory assessments of the FMF patients were performed during attack-free periods. Erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), rheumatoid factor (RF), and anti-CCP antibody levels were measured. In RA patients' ESR and CRP levels, frequency of RF, and anti-CCP antibody levels were significantly higher than in both FMF patients and healthy controls (p 0.001). Moreover, anti-CCP was negative in all healthy controls as well as in all FMF patients. Our results show that anti-CCP antibodies are not associated with FMF.

Efficacy of Shenshi Qianghuo Dihuang Decoction in rheumatoid arthritis: a randomized controlled trial

In China, patients with rheumatoid arthritis (RA) are often treated with traditional Chinese herbal medicine. There are certain advantages of traditional Chinese medicine therapy in treatment of RA. To assess the efficacy and adverse reaction of Shenshi Qianghuo Dihuang Decoction (SQDD), a compound traditional Chinese herbal medicine, in treatment of RA. This was a 24-week prospective, randomized, controlled trial. Ninety RA patients meeting inclusion criteria from Shanghai Municipal Hospital of Traditional Chinese Medicine were randomly assigned to receive SQDD or methotrexate (MTX) with 45 cases in each group. The patients in SQDD group were orally administered with SQDD twice daily, and the patients in MTX control group were treated by oral administration of 15 mg MTX once a week. All the RA patients were treated for 24 weeks. The primary outcome was the number of patients achieving the American College of Rheumatology 20% response. Clinical and laboratory parameters including tender joint count and swollen joint count, patient's global assessment and physician's global assessment (using a 0-10 cm visual analogue scale), duration of morning stiffness, plasma C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR) and value of anti-cyclic citrullinated peptide (CCP) antibody were assessed. After 24-week treatment, the response rates in SQDD group and MTX group were 62.53% (24/41) and 67.5% (28/40) respectively, and there was no statistical difference between the two groups (P>0.05). The patient's global assessment and physician's global assessment, morning stiffness, grip strength, tender joint count, swollen joint count and the levels of ESR, CRP and anti-CCP antibody in SQDD and MTX groups were improved significantly as compared with those before treatment, and there were no significant differences between the two groups. The efficacy of MTX in improving rest pain and joint tenderness was better than that of SQDD (P<0.05). The incidence rate of adverse reactions in SQDD group was 9.75%(4/41), significantly lower than 32.5% (13/40) in MTX group (P<0.05). SQDD has a therapeutic effect on RA, and the adverse reactions are less than MTX.

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.

Anti-cyclic citrullinated peptide antibody (anti-CCP antibody) is present in the sera of patients with dementia of Alzheimer’s type in Asian

In the hippocampi of Alzheimer's disease (AD) patients, aberrant expression of citrullinated proteins and peptidylarginase 2 (PADI2) has been identified. We explored the functional roles of these proteins by means of detection of serum anti-cyclic citrullinated peptide antibody (anti-CCP antibody) in patients with dementia of Alzheimer's type (DAT). Sera were obtained from 42 patients with DAT, 30 patients with other neurological disorders and 42 healthy controls. Gender ratio and age were comparable among the three groups. The level of anti-CCP antibody in sera was examined by ELISA. Anti-CCP antibody was not found in the 30 patients with other neurological disorders, and only one of the 42 healthy controls (2.4%) was positive. However, surprisingly, anti-CCP antibody was clearly detected in eight of the 42 DAT patients. Anti-CCP antibody appears to be a simple and early serologic biomarker for DAT among dementia patients. Additionally, our data imply that citrullinated proteins accumulated in the astrocytes of AD patients acquire neo-antigenicity, inducing anti-CCP antibody production.

Anti-agalactosyl IgG antibodies in Thai patients with rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis

This study was performed to determine the prevalence of anti-agalactosyl IgG antibodies in Thai patients with RA, systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), and determine the sensitivity and specificity of anti-agalactosyl IgG antibodies in the diagnosis of RA in comparison with IgM-rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Serum samples were obtained from 100 patients with RA, 50 cases of SLE, 50 cases of SSc, and 100 healthy controls and analyzed for the presence of anti-agalactosyl IgG antibodies, IgM-RF and anti-CCP antibodies. A serum value greater than mean + 2 standard deviation of normal value of anti-agalactosyl IgG antibodies and anti-CCP antibodies was considered positive. The prevalence of anti-agalactosyl IgG antibodies in RA, SLE, and SSc patients was 88.0%, 14.0%, and 12.0%, respectively. The serum level of anti-agalactosyl IgG antibodies in patients with RA (227.10 +/- 353.64 AU/mL) was significantly higher than those in SLE (11.84 +/- 52.04 AU/mL), SSc (18.85 +/- 99.60 AU/mL), and healthy controls (2.14 +/- 1.97 AU/mL), (p < 0.001). There was a good correlation between the log serum level of anti-agalactosyl IgG antibodies and IgM-RF (r = 0.92, p < 0.001), anti-CCP antibodies and IgM-RF (r = 0.49, p < 0.001), and anti-agalactosyl IgG antibodies and anti-CCP antibodies (r = 0.55, p < 0.001). The sensitivity and specificity in the diagnosis of RA was 88.00% and 96.00% for anti-agalactosyl IgG antibodies, 90.00% and 99.00% for anti-CCP antibodies, and 91.00% and 95.00% for IgM-RF, respectively. The serum level of anti-agalactosyl IgG antibodies was significantly higher in RA than in SLE, SSc, and healthy controls. There was a good correlation between serum levels of anti-agalactosyl IgG antibodies, anti-CCP antibodies, and IgM-RF. These three tests had comparable sensitivity and specificity.

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.

Prevalence of anti cyclic citrullinated peptide antibodies in Malaysian rheumatoid arthritis patients and its correlation with disease activity

The objectives of this study are to provide data regarding the prevalence of anti-cyclic citrullinated peptide (CCP) antibodies in Malaysian rheumatoid arthritis (RA) patients and to correlate the levels of anti-CCP antibody with the Disease Activity Score (DAS). We studied the prevalence of anti-CCP antibodies in 51 RA patients attending our clinic and 29 controls. We also looked for correlation between anti-CCP antibody levels with the DAS and parameters such as duration of disease, rheumatoid factor (RF) and disease-modifying anti rheumatic drug (DMARD) usage. None of the controls demonstrated anti-CCP antibodies. Forty-one out of 51 patients (80.4%) were positive for anti-CCP antibodies. Sensitivity and specificity were 80.4% and 100% respectively in this study. Anti-CCP levels correlated significantly with rheumatoid factor, but no correlation was observed with the other parameters. Anti-CCP antibody is prevalent in Malaysian RA patients at 80.4% and more sensitive than RF in our cohort of established RA patients. Even though the anti-CCP levels correlated with RF, it did not show correlation with DAS.

Third generation anti-cyclic citrullinated peptide antibodies do not predict anti-TNF-α treatment response in rheumatoid arthritis

Objective of this study is to retrospectively compare the third generation anti-cyclic citrullinated peptide (anti-CCP3) test with the second generation (anti-CCP2) assay as markers of disease activity and predictors of clinical response in rheumatoid arthritis (RA) patients treated with TNF-alpha blocking agents. This study was performed in 42 RA patients treated either with infliximab (n = 11), etanercept (n = 7) or adalimumab (n = 24). Serum anti-CCP3 and anti-CCP2 levels were tested before and 6 months after starting a TNF-alpha blocking treatment using commercially available ELISA kits. Anti-CCP3 and anti-CCP2 antibody levels did not significantly change after 6 months of TNF-alpha blocking treatment. Furthermore, neither anti-CCP3 nor anti-CCP2 was useful to predict anti-TNF-alpha treatment response using receiving operating characteristic curve and logistic regression analyses. Both anti-CCP3 and anti-CCP2 are not differentially influenced by TNF-alpha blocking agents in RA patients and failed to predict anti-TNF-alpha treatment response.