Presence Of anti-CCP Antibodies Research Articles

Some Aspect of Accuracy of Acpa Assay in Patients with Psoriatic Arthritis

Aims:To compare the values and acuracy of the test in anticyclic citrullinatedpeptides (Anti-CCP /ACPA) antibodies, Rheumatoid factor (RF), C-Reactive Protein (CRP) and disease activity index (PASI) in early diagnosis of untreated Psoriatic arthritis(PsA).Methods:Using the ELISA method of DIA-STATTM Anti CCP (Axis–Shield Diagnostics), sera of 70 participants were examined (35 untreated patients with PsA and 35 persons from the healthy control group). RF and CRP were determined with the agglutination test (Lateks test) in the same participants. In the same time we determined the sensitivity, specificity, predictive value for positive and negative test and accuracy.Results:From 35 pts with PsA, 1 patient showed presence of Anti-CCP antibodies (sensitivity test 2.86%), while RF was present in 0 pts (sensitivity test 0%). In the healthy control group positive values for RF, CRP and Erythroid Sedimentation Rate (ESR) were detected in 1 participant.Conclussion:ACPA antibodies have low sensitivity, but high specificity in PsA.Key words: Anti cyclic citrullinated peptide (Anti-CCP) Psoriatic arthritis (PsA), Rheumatoid factor (RF)

To Study The Prevalence of Ocular Manifestations in Rheumatoid Arthritis And their Correlation with Anti Cyclic Citrullinated Peptide Antibodies And Rheumatoid Factor .

Introduction: Ocular involvement in rheumatoid arthritis (RA) is significant as sometimes if missed can be potentially blinding.Their presence also aids in making the final diagnosis of RA with atypical presentation. During the course of treatment of RA ,flaring of ocular signs and symptoms may signal impending deterioration or relapse of RA . Thus the study was undertaken in our tertiary care hospital to know the prevalence of ocular manifestations in patients of RA and their correlation with disease activity. Material and Methods: The present prospective observational study was conducted in Regional Institute of ophthalmology on 139 patients of rheumatoid arthritis. Detailed ocular examination was done and besides routine investigations RA factor(RF) and anti cyclic citrullinated peptide antibodies(ACCP) of each patient was recorded.Chi-square test was used to correlate their significance to ocular manifestations. Probability (p) value less than 0.05 was considered significant. Results: Among 139 patients of rheumatoid arthritis included in our study , 53(38%) patients had ocular signs and symptoms. 31(22 %) patients had dry eye,13(9%) had keratoconjunctivitis sicca(KCS), 7 (5%) had anterior uveitis , 4(3%) had episcleritis, 3(2%) had scleritis, 2(1.4%) had peripheral ulcerative keratitis(PUK), 2(1.4%) had sclerosing keratitis, 5(3.5%) had cataract,and1(0.7%) had rental vasculitis. The prevalence of ocular manifestations was significantly higher in patients with positive serology than those with negative serology (p .05) Conclusion: Patients of rheumatoid arthritis need to get routine ocular examination for the early diagnosis and timely management so as to prevent permanent irreparable loss of vision. The presence of anti CCP antibodies and RF provides effective clue to ophthalmologists for identifying patients at risk for vision threatening inflammatory ocular complications.

Disease Activity, Oxidized-LDL Fraction and Anti-Oxidized LDL Antibodies Influence Cardiovascular Risk in Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) have a shortened lifespan compared to the general population. The high rate of premature mortality in the RA population can be attributed to cardiovascular disease (CVD). The aim of the study was to look for non-classic risk factors that can at least partially explain the enhanced cardiovascular (CV) risk in patients with RA. This was an observational study with 37 RA patients and 24 healthy volunteers as controls. The participants' medical history was taken, and systematic coronary risk evaluation (SCORE) and carotid ultrasonography examinations were performed on all the participants. Laboratory tests included antibodies anti-cyclic citrullinated peptide (anti-CCP), inflammatory markers, lipid level, oxidized low-density lipoprotein (oxLDL) level and the level of anti-oxLDL antibodies. Both SCORE and oxLDL fraction were elevated in RA patients as compared to the healthy controls (3.1 ± 3.7 vs. 0.8 ± 1.2, p = 0.005; and 0.029 ± 0.033% vs. 0.014 ± 0.006%, p = 0.04, respectively). In the RA group, the presence of anti-CCP was associated with thickening of the carotid intima-media complex and SCORE elevation. In the RA group, significant correlations were found between SCORE and mean carotid intima-media thickness (IMT; RP = 0.34, p = 0.040), disease activity score (RP = 0.42, p = 0.011), erythrocyte sedimentation rate (ESR; RP = 0.35, p = 0.036), and disease duration (RP = 0.52, p = 0.002). In RA patients with carotid plaques, the oxLDL fraction was significantly elevated in comparison to those without plaques (0.055 ± 0.070% vs. 0.022 ± 0.018%, p = 0.033). In the RA group, there was a significant negative correlation between mean carotid IMT and the serum concentration of anti-oxLDL antibodies (RP = -0.38, p = 0.02). No association was noted between the presence of rheumatoid nodules and SCORE or carotid IMT. Among RA patients, disease activity, ESR, disease duration, the presence of anti-CCP antibodies, the oxLDL fraction and the level of anti-oxLDL antibodies influence CV risk.

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...

A116: Increased Antibody Responses to Porphyromonas Gingivalis in Children With Anticyclic Citrullinated Peptide Antibody‐Positive Juvenile Idiopathic Arthritis

Background/Purpose:Rheumatoid arthritis (RA) is an inflammatory arthritis typically presenting in women in their fifth decade. Most individuals with RA have antibodies to citrullinated peptide antigens, such as anti‐cyclic citrullinated peptide antibodies (CCP). In addition to genetic factors, cigarette smoking and periodontal disease (PD) secondary to Porphyromonas gingivalis are risk factors for RA. Some children with juvenile idiopathic arthritis (JIA) phenotypically resemble adults with seropositive RA, characterized by the presence of anti‐CCP antibodies. Our objective was to investigate the association between anti‐CCP antibodies and anti‐P. gingivalis antibodies, as well as the association between anti‐CCP antibodies and symptoms of PD, in children with CCP‐positive (CCP+) JIA vs. children with CCP‐negative (CCP−) JIA.Methods:Study participants included 77 children with CCP+JIA and 130 children with CCP‐JIA. Antibodies to P. gingivalis, P. intermedia, and F. nucleatum outer membrane antigen were measured using ELISA in 71 children with CCP+JIA and 74 children with CCP‐JIA. Oral health history and smoke exposure history were collected using a parent questionnaire from 37 children with CCP+JIA and 127 CCP‐JIA. T‐tests were used to compare means between the two groups; Chi‐Square or Fisher's tests were used to compare categorical variables.Results:Children with CCP+JIA were more likely to be female (89% vs. 64%), older at the time of diagnosis (10.3 vs. 6 years), and either African American (29.9% vs. 11%) or Hispanic (17% vs. 9.2%) compared to children with CCP‐JIA. Anti‐P. gingivalis IgG antibody titers were significantly higher in the CCP+JIA cohort than in the CCP‐JIA cohort (9.04 vs. 5.69; p < 0.003). Anti‐P. intermedia IgG and anti‐F. nucleatum IgG antibody titers were not different between the two groups. There was no association between CCP+JIA and smoke exposure in the prenatal period or in the 6 months prior to JIA symptom onset. Several symptoms of poor oral hygiene were higher among children with CCP+JIA: red/swollen gums (35% vs. 20%, p < 0.08), tender bleeding gums (41% vs. 24%, p < 0.06), pain on chewing (38% vs. 18%, p < 0.03), and never/rarely flossing (49% vs. 32%, p < 0.08). Of note, there was no significant difference in the frequency of cavities between children with CCP+JIA and children with CCP‐JIA. When oral health comparisons were limited to Non‐Hispanic white subjects, red/swollen gums (p < 0.003) and tender bleeding gums (p < 0.002) were even more prevalent in children with CCP+JIA compared to children with CCP‐JIA.Conclusion:We have shown that children with CCP+JIA have higher titers of antibodies to P. gingivalis compared to children with CCP‐JIA. Furthermore, children with CCP+JIA appear to have symptoms of poor oral health. There was no association between smoke exposure and CCP+JIA. To our knowledge, this is the first study to explore the relationship between these risk factors and the onset of CCP+JIA.

Therapeutic potential of hydroxychloroquine on serum B-cell activating factor belonging to the tumor necrosis factor family (BAFF) in rheumatoid arthritis patients

ObjectiveTo assess the serum B-cell activating factor belonging to the tumor necrosis factor family (BAFF) level in rheumatoid arthritis (RA) patients in view of different treatment regimens received and evaluate its relation with disease activity. Patients and methodsNinety female RA patients were included. Sixty were on disease modifying anti-rheumatic drugs (DMARDs); 34 on hydroxychloroquine (HCQ) plus methotrexate (MTX), 26 on leflunomide (LFN) plus MTX and 30 newly diagnosed cases not yet on any treatment. Thirty age and gender matched healthy subjects served as controls. Full history taking, clinical examination and relevant laboratory investigations were performed. Disease activity score, in 28 joints (DAS-28), was calculated. ResultsSerum BAFF level was significantly higher in patients (1.82±0.91ng/ml) compared to control (0.71±0.33ng/ml; p<0.001). There was a significantly lower BAFF and disease activity in patients receiving DMARDs (1.55±0.73ng/ml and 3.08±0.73) compared to new cases (2.36±1.02ng/ml and 3.46±0.82) (p<0.001 and p=0.036, respectively). Those receiving HCQ+MTX had a lower BAFF level (1.29±0.51ng/ml) compared to those receiving LFN+MTX (1.94±0.85ng/ml; p=0.002). The BAFF level significantly correlated with the presence of anti-CCP antibodies, DAS28 and MTX dose in all RA patients (r=0.24, p=0.02; r=0.504, p<0.001; r=0.51, p<0.001, respectively). Only DAS28 and MTX dose would highly influence the BAFF level (p=0.015 and p=0.001, respectively). ConclusionElevated level of BAFF in RA has been confirmed with a notable relation to disease activity making it a promising marker. The beneficial effect of hydroxychloroquine in dampening BAFF level throws light on the importance of considering it in combination among the newly developed biologics that also target B-cells.

Circulating anti-cyclic citrullinated peptide antibody in patients with rheumatoid arthritis and chronic obstructive pulmonary disease

Anti-cyclic citrullinated peptide (anti-CCP) antibody is highly specific for diagnosing rheumatoid arthritis (RA). Cigarette smoking is a lifestyle and environmental factor associated with anti-CCP production and is strongly associated with chronic obstructive pulmonary disease (COPD). This study assessed levels of anti-CCP antibodies and rheumatoid factor (RF) among patients with RA and COPD. The study sample comprised 63 patients with RA and 70 patients with COPD, all of whom underwent assessment of anti-CCP antibody and RF levels. Testing revealed that 54.2% of RA patients and 0% of COPD patients were positive for anti-CCP antibodies. Additionally, 82.5% of RA patients and 42% of COPD patients were positive for RF. Among RA patients, levels of anti-CCP antibodies were higher among smokers than among nonsmokers (242.7 ± 128.3 vs. 68.1 ± 112.1, P < 0.001). COPD patients had low titers of RF but were negative for anti-CCP antibodies. The presence of anti-CCP antibodies was a reliable serologic marker in RA diagnosis and was associated with cigarette smoking.

FRI0247 Serum level of interleukin 33, a novel independent predictive biomarker of clinical response to rituximab in rheumatoid arthritis: results from the smart trial

BackgroundInterleukin-33 (IL33) is a recently identified member of the interleukin-1 family that binds to its ST2 receptor expressed on various cells including mast cells, T-cells and also B1-cells in mice...

OP0134 Risk stratification in patients with undifferentiated arthritis according to the 2010 ACR/EULAR criteria

BackgroundEarly recognition and treatment of Rheumatoid Arthritis (RA) is associated with an improved outcome. The 2010 ACR/EULAR criteria for RA identify RA patients earlier than the 1987 criteria. Nevertheless, we...

AB0057 Soluble pd-1 and spd-l2 are unaffected by adalimumab treatment in early ra and associated with presence of anti-ccp and igm-rf

BackgroundDisturbance of the balance in the immune system plays a major role in rheumatoid arthritis (RA). Programmed Death 1 (PD-1) expressed by activated T cells and its ligand (PD-L2) expressed...

AB0284 Local and systemic (ESPOIR cohort) human soluble fadd is a new inflammatory marker in rheumatoid arthritis

BackgroundFas-associated death domain (FADD) is the key adaptor transmitting the apoptotic signal mediated by death receptors. It is also implicated in numerous non apoptotic functions. In particular, FADD is a...

FRI0111 Unexpected finding of anti-citrullinated protein antibodies (ACPA) in cerebrospinal fluid of RA patients with intact blood brain barrier - potential for autoimmune reactions in the CNS

BackgroundArthritis is known to associate with upregulation of inflammatory mediators in the central nervous system (CNS) as shown in earlier experimental studies (1). However, little is known about the possible...

The diagnostic utility of matrix metalloproteinase-3 and high-sensitivity C-reactive protein for predicting rheumatoid arthritis in anti-cyclic citrullinated peptide antibody-negative patients with recent-onset undifferentiated arthritis

Anti-cyclic citrullinated peptide (anti-CCP) antibodies are well-established serological markers that show high sensitivity and specificity in early rheumatoid arthritis (RA) and are associated with bone erosions of RA. However, some patients subsequently progress to RA even if there is no presence of anti-CCP antibodies in an early stage. The aim of this study is to evaluate the diagnostic utility of matrix metalloproteinase-3 (MMP-3), high-sensitivity C-reactive protein (hsCRP) and IgM rheumatoid factor for predicting RA in anti-CCP-negative patients with recent-onset undifferentiated arthritis (UA). Baseline levels of those markers were measured at the entry of the study. A total of 99 patients with UA were included, among them 44 patients (44.4 %) had been classified as having RA by a skilled rheumatologist at some point during 1-year follow-up. Of these 99 patients, 34 patients (34.3 %) had anti-CCP antibodies and 65 patients (65.7 %) had no anti-CCP antibodies. Eleven patients who were anti-CCP-negative developed RA. We compared sensitivity, specificity, positive predictive value and negative predictive value of serum markers of these anti-CCP-negative RA patients. The combined usage of MMP-3 with hsCRP is relatively superior to other markers as predictors of RA.

Anti-CCP Antibodies Are Not Associated with Familial Mediterranean Fever in Childhood

Objective. Anticyclic citrullinated peptide antibodies (anti-CCP) testing is useful in the diagnosis of rheumatoid arthritis (RA) with high specificity. Arthritis is a very common clinical manifestation in children with familial Mediterranean fever (FMF). The aim of the study was to show the presence of anti-CCP antibodies in child individuals diagnosed with FMF. Material and Methods. The study groups comprised one hundred and twenty-six patients (126) diagnosed with FMF (female/male (n): 66/60) and 50 healthy controls (female/male (n): 25/25). Clinical and laboratory assessments of the FMF patients were performed during attack-free periods. Erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), fibrinogen, and anti-CCP antibody levels were measured. Results. Anti-CCP was negative in healthy controls and also in all FMF patients. There was not a significant difference in anti-CCP between the patient and the control groups. Our study has shown that anti-CCP was correlated moderately with age (rs = 0.271; P = 0.0020), duration of illness (rs = 0.331; P < 0.0001), and colchicine therapy (rs = 0.259; P = 0.004). Conclusion. Our data show that anti-CCP antibodies are not associated with FMF. Anti-CCP does not have a priority for identifying FMF arthritis from the other inflammatory arthritis.

The relationship between peripheral arthritis and anti-cyclic citrullinated peptide antibodies in ankylosing spondylitis

ObjectivesAlthough ankylosing spondylitis (AS) primarily affects the axial skeleton, peripheral arthritis occurs in up to 35% of cases. Anti-cyclic citrullinated peptide (anti-CCP) antibodies are highly specific for rheumatoid arthritis, whereas their role in AS remains unclear. In this study we aimed to assess the prevalence of anti-CCP antibodies in AS patients with peripheral arthritis and their clinical association with peripheral arthritis. MethodsWe retrospectively selected for this study 625 AS patients who fulfilled the modified New York criteria. The patients were divided into those with and those without peripheral arthritis on smoking history, the basis of symptoms, physical examination and medical records. The presence of anti-CCP antibodies was investigated in all the patients. ResultsAnti-CCP antibodies were found in 4% (25/625) of the patients, and peripheral arthritis was diagnosed in 37.4% (234/625) of the patients. In multiple logistic regression, peripheral arthritis was significantly associated with female gender (P=0.001) and the presence of anti-CCP antibodies (P=0.001), especially with the presence of titers of anti-CCP antibodies over three times the normal upper limit of the laboratory and assay. ConclusionsAnti-CCP antibodies are occasionally present in AS, and their presence may be helpful as a serum marker for predicting peripheral arthritis.

Expression of peptidylarginine deiminase‐2 and ‐4, citrullinated proteins and anti‐citrullinated protein antibodies in human gingiva

The presence of citrullinated proteins, and peptidylarginine deiminase types -2 (PAD-2) and -4 (PAD-4) in periodontal tissues, determine the presence of anti-cyclic citrullinated protein antibodies (anti-CCP) in gingival crevicular fluid (GCF) and compare the expression of these proteins between inflamed and non-inflamed sites. Tissue sections were stained using antibodies against citrullinated proteins, PAD-2 and PAD-4. RT-PCR was performed to investigate PAD-2 and PAD-4 mRNA in inflamed and non-inflamed gingival tissues. Anti-CCP antibodies in gingival crevicular fluid were detected by ELISA. Citrullinated proteins, PAD-2 and PAD-4 were detected in gingiva. There was a correlation between inflammation and expression of these proteins. mRNAs for PAD-2 and PAD-4 were detected in both inflamed and non-inflamed gingival tissues. Antibodies to CCP were found mostly in the GCF of individuals with periodontitis. PAD-2 and PAD-4 (protein and mRNA) as well as citrullinated proteins are present in inflamed gingiva, and anti-CCP antibodies can be detected in the GCF of some patients. Tissue expression of citrullinated proteins and PAD increased with the severity of inflammation. The presence of anti-CCP antibodies in GCF was almost exclusive to a subset of patients with periodontitis. Increased expression of these proteins in inflamed gingiva lends support to the notion that periodontal inflammation contributes to the inflammatory burden in a similar way to rheumatoid arthritis.

Unexpected finding of anticitrullinated protein antibodies in cerebrospinal fluid of RA patients with intact blood brain barrier

BackgroundThe authors have recently shown upregulation of inflammatory mediators in cerebrospinal fluid (CSF) from patients with rheumatoid arthritis (RA), with correlations to fatigue mechanisms. The authors have now sought to...

B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: A six‐month, national, multicenter, open‐label study

To examine whether serum B cell markers can predict response to rituximab, a B cell-depleting monoclonal antibody, in patients with refractory rheumatoid arthritis (RA). This rituximab re-treatment dose study (SMART [eSsai MAbthera sur la dose de Re-Traitement]) involved 208 patients with refractory RA. Serum markers of B cell activation (anti-cyclic citrullinated peptide [anti-CCP] antibodies, rheumatoid factor [RF], serum IgG, IgA, and IgM levels, serum κ and λ free light chains, and serum BAFF) were assessed before the first rituximab cycle (1,000 mg on days 1 and 15). Univariate and multivariate analyses were performed to identify factors associated with a European League Against Rheumatism (EULAR) response at 24 weeks. There were 149 responders (72%). Two baseline factors were associated with a EULAR response at 24 weeks in multivariate analysis: the presence of anti-CCP antibodies or RF (odds ratio 3.5 [95% confidence interval 1.6-7.6]) and a serum IgG concentration above normal (odds ratio 2.11 [95% confidence interval 1.02-4.33]), with synergy between them (odds ratio 6.0 [95% confidence interval 2.2-16.2]). The presence of RF or anti-CCP antibodies and elevated IgG are 2 simple biomarkers that can be used routinely before therapy to predict response to rituximab in patients with refractory RA.

The Role of Anti-Cyclic Citrullinated Peptide Antibody in Periodontal Disease

The anti-Cyclic Citrullinated Peptide Antibodies (anti-CCP) are produced locally in the inflamed synovium of Rheumatoid arthritis (RA) patients, suggesting that citrullinated proteins are located in the inflamed synovium. In scientific literature were find periodontal bacterial DNA in serum and synovial fluid of RA with PD patients. RA and adult periodontitis share common pathogenetic mechanisms and immunologic and pathological findings RA. One oral pathogen strongly implicated in the pathogenesis of periodontal disease (PD), Porphyromonas. gingivalis, possesses a unique microbial enzyme, peptidylarginine deiminase (PAD), the human equivalent of which has been identified as a susceptibility factor for RA. Under this point of view, we speculate about the presence of anti-CCP antibodies in sera of PD with RA patients. We conducted this study to evaluate and compare the diagnostic and predictive utility of anti-CCP antibodies in patients with PD and patients with PD and RA. Anti-CCP antibody was not found in 21 sera (U/ml<10), included RA controls, while only 1 patient with chronic PD and probing depth of 7,1 mm was identified positive for anti-CCP (22.2 U/ml). Our data do not support a role for anti-CCP in diagnoses of periodontal disease.

Smoking increases rheumatoid arthritis susceptibility in individuals carrying the HLA–DRB1 shared epitope, regardless of rheumatoid factor or anti–cyclic citrullinated peptide antibody status

Smoking is associated with rheumatoid arthritis (RA) in individuals with the HLA-DRB1 shared epitope (SE). SE alleles have been shown to be predominantly associated with anti-cyclic citrullinated peptide (anti-CCP)-positive RA. These risk factors have not been identified for anti-CCP-negative RA. The aim of this study was to investigate whether SE-containing HLA-DRB1 alleles, smoking, or the combination of these factors contributes to the development of RA, depending on the presence or absence of serologic markers, in a Korean population. All of the patients with RA (n =1,482) and all of the control subjects (n = 1,119) were Korean. Four-digit HLA-DRB1 typing was performed by a conventional polymerase chain reaction-sequence-based typing method. Information about smoking history was obtained through a questionnaire. The patients with RA were tested for anti-CCP antibodies and rheumatoid factor (RF). The SE alleles had significant effects on anti-CCP antibody and RF formation. The DRB1*0901 allele was associated with the presence of anti-CCP antibodies (odds ratio [OR] 2.49) and RF (OR 2.09). SE alleles and smoking were associated with both anti-CCP-positive and anti-CCP-negative RA. The combination of smoking and double copies of the SE allele increased the risk of anti-CCP-positive RA 36.11-fold and increased the risk of anti-CCP-negative RA 12.29-fold, compared with the risk among nonsmokers not carrying SE alleles. Interactions between SE alleles and smoking were observed for both anti-CCP-positive and RF-positive RA, although the associations of RF-positive RA could be consequences of the underlying anti-CCP antibody status. We demonstrated that the combination of SE alleles and smoking is associated with RA susceptibility regardless of anti-CCP antibody or RF status, but that the combination shows stronger effects in anti-CCP-positive/RF-positive patients with RA than in anti-CCP-negative/RF-negative patients with RA. The SE-smoking interactions were present in anti-CCP-positive and RF-positive RA.