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ObjectivesTo investigate the clinical value of detecting anti–mutated citrullinated vimentin (anti-MCV), anti-citrullinated peptide (anti-CCP), red-blood-cell distribution width (RDW), and 25-hydroxyvitamin D (25-[OH]D) in the diagnosis of rheumatoid arthritis (RA).MethodsWe enrolled 119 patients with RA, 114 control individuals without RA (disease controls), and 40 healthy controls in our study (Han Chinese). Anti-CCP and anti-MCV were detected by enzyme-linked immunosorbent assay (ELISA), 25-(OH)D was detected by electrochemical luminescence, and RDW was calculated by erythrocyte parameters detected via the electric resistance method.ResultsThe serum levels of anti-CCP and anti-MCV in RA were higher than those in disease controls and healthy controls (P ConclusionsAnti-CCP and anti-MCV are ideal indices for RA diagnosis. Also, in combination with RDW and 25-(OH)D, the diagnostic level will be improved, as well as the sensitivity and specificity, which is significant for the differential diagnosis of RA.

Background/Aims The effects of antinuclear antibodies (ANA) in rheumatoid arthritis (RA) are not fully characterised. Studies investigating the effect of ANA on disease activity in RA have yielded mixed results. The presence of ANA has been correlated with higher levels of CRP and joint inflammation in RA. Evidence suggests that ANA positivity at baseline may predict poor response to both traditional disease modifying agents and biologic therapy. ANA may also be associated with higher incidences of ocular disease, Felty’s syndrome, vasculitis and subjective pain in RA patients. On the other hand, other studies showed a lack of correlation between ANA status and joint inflammation in RA. Our study investigates the relationship between ANA positivity and joint erosions in rheumatoid patients. Methods This is a cross-sectional study of patients attending the early arthritis clinic at Northwick Park Hospital in London over a five year period (2014-2019). A total of 631 patients were identified of whom 261 had RA. We collected data on the age, gender, ANA positivity, the presence of anti-CCP (anti cyclic-citrullinated peptide) antibodies and rheumatoid factor (RF) at presentation as well as the presence of erosive disease on radiological reports of hand X-rays. Positive ANA was defined as having a titre of 1:80 or greater. Patients with missing ANA result or hand X-ray reports were excluded, leaving 228 patients. Two-tailed Chi-square tests for categorical data and two-tailed student’s t-tests for continuous data were performed to determine the statistical significance of comparisons made between the ANA positive and negative groups. Results Of the 228 patients, 49 (21.5%) were male and 179 (78.5%) were female. The mean age was 58 years. 84 (36.8%) patients were ANA positive (group 1) and 144 (63.2%) were ANA negative (group 2). In group 1, 23/84 (27.4%) patients had erosive disease. In group 2, erosions were found in 25/144 patients (17.4%). This difference was not statistically significant (p = 0.073). The number of patients who were RF positive in groups 1 and 2 were 79.5% and 73.6% respectively (p = 0.317); 75/84 (89.3%) patients in group 1 and 113/143 (79.0%) in group 2 were anti-CCP antibody positive (p = 0.048). The means of the age of patients were 53 and 62 years in group 1 and group 2 respectively (p < 0.0001); the ANA positive group was significantly younger. The male:female ratio was 13:71 in group 1 and 36:108 in group 2 (p = 0.091). Conclusion Our study showed no significant association between ANA status and erosive disease in RA, although a greater proportion of patients had erosions in the ANA positive group. Larger observational studies may better study this relationship. Disclosure T. Guruparan: None. M. Hutchinson: None. R. Hayward: None. H. Penn: None. P. Kalia: None.

Background Anti-citrullinated peptide antibodies (ACPA) are important biomarkers in rheumatoid arthritis (RA) and can predict arthritis development in at-risk individuals. ACPA are conventionally detected using the second-generation or third generation IgG anti-CCP antibody (Ab) assays. Although the value of anti-CCP2 Ab for predicting progression to RA in at-risk individuals is well understood, very little knowledge exists for anti-CCP3.The objectives of this study were: i) To evaluate the prevalence of serum anti-CCP3 Ab in serum anti-CCP2 Ab positive at-risk individuals (CCP2+ at-risk); ii)) To study the incremental value of anti-CCP3 Ab in CCP2+ at-risk subjects for predicting progression to clinical inflammatory arthritis (IA). Methods Anti-CCP3 Ab were tested on stored serum samples obtained from 347 CCP2 + (BioRad, USA) at-risk individuals from the Leeds CCP study. Anti-CCP2 and anti-CCP3 tests positivity threshold was >2.99 IU/ml and >20 units, respectively. Moreover, anti-CCP2 and anti-CCP3 titres were categorised according to manufacturer’s cut-off: low (LT) and high (HT) for anti-CCP2, negative/weak/moderate/strong for anti-CCP3. Progression to IA was defined as the development of clinical synovitis in at least one joint. Only subjects with at least one follow-up visit were included in the progression analysis (n = 317). Results Anti-CCP3 Ab were negative in 138/347 (39.7%) CCP2+ individuals, and weakly, moderately, and strongly positive in 15/347 (4.3%), 5/347 (1.4%) and 189/347 (54.4%) individuals, respectively. LT and HT anti-CCP2 Ab were found in 103/347 (29.7%) and in 244/347 (70.3%) individuals, respectively. Eighty-eight/317 subjects (28%) developed IA. The rate of progression of LT and HT anti-CCP2, when anti-CCP3 was negative, decreased from 6.5% to 2.7%, and from 36.6% to 9.4%, respectively. Progression in anti-CCP2 HT increased from 36.6% to 45.6% when anti-CCP3 was positive (Table 1). Conclusion Our results support an important role for anti-CCP3 Ab in improving prediction of IA in CCP2+ at-risk individuals. Disclosures A. Di Matteo None. K. Mankia None. L. Duquenne None. M. Mahler Other; Inova Diagnostic. D. Corscadden None. K. Mbara None. L. Garcia-Montoya None. J. Nam None. P. Emery Honoraria; AbbVie, BMS, Bristol-Myers Squibb, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, Samsung, Samsung Bioepis Co., Ltd.

Background This study aims to estimate the influence of air pollution ambients using the Air Quality Index (AQI) to Rheumatoid Arthritis (RA) disease activity. Disease Activity Score with 28 examined joints (DAS-28) and Clinical Disease Activity Index (CDAI) considered as disease activity indices for RA patients in the state of Kuwait. Methods Data for patients with RA disease were collected from Kuwait Registry for Rheumatic Diseases (KRRD) from 2013 to 2017. Moreover, data on air pollution obtained from The Kuwait Environmental Public Authority (K-EPA) during the same period. Statistical analysis was conducted using STATA to highlight the significant association between study variables. Descriptive statistics, correlation analysis and linear regression model techniques were employed to estimate the significant associations between RA disease activity represented by DAS-28 and CDAI; with air pollution components (PM10, NO2, SO2, O3, and CO). Multiple Imputation by Chained Equations (MICE) algorithm was also employed to tackle the value of the missing data for air pollution data. Results Total of 9,875 patients visits included in the analysis that matching with air pollution information from K-EPA database according to date and patient living address governorate. The study found SO2 and NO2 were significantly associated with RA disease activity using DAS-28 index, also, for CDAI index as well. For the score of RA disease activity using DAS-28 index, the correlation results show a positive significant correlation with exposure of SO2 using AQI (rp = 0.07), also the same results with the with the exposure of NO2 using AQI (rp = 0.07). The final model is demonstrating the effect from air-pollutants gaseous with RA factors (Swollen, RF, anti-CCP, ESR, CRP) on RA disease activity. The AQI of NO2 and SO2 still showed positive associations with disease activity performance of RA. The linear regression model shows a positive effects of NO2 (beta = 0.003, 95% CI: 0.002-0.005) and (beta = 0.048, 95\% CI: 0.030-0.066) for DAS-28 and CDAI respectively, where for SO2, the results shows positive significant effect with (beta = 0.003, 95% CI: 0.0004-0.005) and (beta = 0.044, 95% CI: 0.018-0.070) for DAS-28 and CDAI respectively. Conclusion In conclusion, our study showed that air ambients were significantly correlated to RA disease activity scores and should be considered as a possible risk factor for RA activity. Disclosures A.R. Alsaber None. J. Pan None. A. Al-Herz None. D.S. Alkandary None. A. Al-Hurban None. P. Setiya None.

Background The presence of antibodies against cyclic citrullinated proteins (anti-CCP) precede the development of rheumatoid arthritis (RA) and both anti-CCP antibody and RF positivity indicate more severe disease. This characteristic makes Anti-CCP best biomarker candidate for the prevention of debilitating joint disease. Almost 70% of RA patients are positive for anti-CCP IgG, while only 2% of control subjects are positive for anti-CCP. Understanding the origins of anti-CCP is critical in unraveling the etiology of RA, so we further evaluated the association of the other autoimmune tests/biomarkers with Anti-CCP to describe other comorbid autoimmune diseases/syndrome. Methods We conducted a retrospective analysis of patient data from April 18, 2016, to May 29, 2019, in Texas. The study protocol was approved by the ethics review committee and patients consented for sharing their demographics, clinical information and lab values for diagnostic and research purposes. The study population was described by descriptive statistics. Demographic characteristics and laboratory parameters were compared using chi-square tests. We analyzed blood tests/parameters conducted at the clinics and explored their association with the presence of ACCP. logistic regression models were utilized to calculate the odds ratio to delineate the strength of association of different blood parameters with ACCP. IgG anti-CCP was determined according to the manufacturer’s instruction. Results Eleven thousand, four hundred fifty-nine tests were performed on 7,200 patients with a mean age of 52 years (range 0-98). Almost half (54%) of study individuals were females, two-third (63%) were White, (29%) Hispanic and (7%) African American. Four hundred and six patients (3.5%) were positive for AntiCCP3.1. Among those who were positive for AntiCCP3.1, (22%) were Rh factor IgA (RhIgA) positive, (11%) RhIgG positive, and (9%) RhIgM. Univariate logistic regression showed that the female gender was positively associated (OR = 3.19) with ACCP presence while patients older than 50 had a positive gradient of ACCP positivity with each age category. Compared to White, African Americans were more likely (OR = 3.19) and Hispanics were less likely (OR = 0.44) to be associated with AntiCCP positivity. After controlling for age, gender and ethnicity the presence of RhIgM and RhIgA antibodies were positively associated with positive ACCP. (OR = 13.3, OR = 5.2). antiphosphatidylserine IgM and anticardiolipin IgM antibodies were positively associated with ACCP (OR = 2.1, OR = 3.4). Similarly, the presence of antimitochondrial M2 antibodies and anti-topoisomerase antibodies (SCL-70) were very significantly associated with ACCP (OR = 16.1, OR = 37.8). Conclusion The Anti-CCP antibodies are highly specific for the early diagnosis of RA and with early initiation of treatment, progression to irreversible and destructive diseases can be prevented. Association of Anti-CCP antibodies with other autoimmune antibodies highlights the importance of screening RA patients for primary biliary sclerosis and scleroderma. Similarly, a biomarker's strength of interaction with another biomarker helps in the prognostic utility of these test for preventing co-existing diseases. Disclosures M. Ayass: Other; Physician at Ayass Bioscience. K. Zhu: Other; Employee at Ayass Bioscience. S. Naveed: None. L. Mosleh: Other; Employee at Ayass Bioscience. K. Viswanathan: Other; Employee at Ayass Bioscience. G. Nowshad: Other; Employee at Ayass Bioscience.

ObjectivesLittle is known about the likelihood of developing inflammatory arthritis (IA) in individuals who screen autoantibody positive (aAb+) in a non-clinical research setting.MethodsWe screened for serum cyclic citrullinated peptide antibody (anti-CCP) and rheumatoid factor isotype aAbs in subjects who were at increased risk for rheumatoid arthritis (RA) because they are a first-degree relative of an individual with classified RA (n=1780). We evaluated combinations of aAbs and high titre aAbs, as defined by 2-times (2 x) the standard cut-off and an optimal cut-off, as predictors of our two outcomes, aAb+ persistence and incident IA.Results304 subjects (17.1%) tested aAb+; of those, 131 were IA-free and had at least one follow-up visit. Sixty-four per cent of these tested aAb+ again on their next visit. Anti-CCP+ at levels ≥2 x the standard cut-off was associated with 13-fold higher likelihood of aAb +persistence. During a median of 4.4 years (IQR: 2.2–7.2), 20 subjects (15.3%) developed IA. Among subjects that screened anti-CCP+ at ≥ 2 x or ≥an optimal cut-off, 32% and 26% had developed IA within 5 years, respectively. Both anti-CCP cut-offs conferred an approximate fourfold increased risk of future IA (HR 4.09 and HR 3.95, pConclusionsThese findings support that aAb screening in a non-clinical setting can identify RA-related aAb+ individuals, as well as levels and combinations of aAbs that are associated with higher risk for future IA. Monitoring for the development of IA in aAb+ individuals and similar aAb testing approaches in at-risk populations may identify candidates for prevention studies in RA.

We studied the diagnostic value of high-frequency color Doppler ultrasonography (HCDU) examination in combination with anti-cyclic citrullinated peptide (anti-CCP) antibody testing in rheumatoid arthritis (RA) patients with finger joint damage. From January 2015 to December 2015, 80 patients diagnosed with RA with finger joints damage were enrolled in this study. Patients were examined with HCDU. Serum anti-CCP antibody level was tested using ELISA, and results were compared with the healthy control group. Results obtained by ELISA demonstrated that the positive rate of anti-CCP antibodies was 73.8% in the study group, and 10% in the control group. The negative rate was 26.2% in the study group, and 90% in the control group. HCDU examination suggested that the predominantly affected joint by bone erosion of RA with finger joint damage was MCP3 (16.7%), followed by PIP3 (14.1%), MCP2 (13.5%) and PIP2 (12.8%). The slightest affected joint was thumb metacarpophalangeal joint, followed by thumb, little finger metacarpophalangeal joint and proximal interphalangeal joint. The sensitivity of diagnosis of RA with finger joints damage with both HCDU and CCP antibody examination showed a significantly lower level compared with examination with each one of the methods alone, while specificity showed a significantly higher level. Thus, a combination of HCDU examination and anti-CCP antibody testing can be considered useful to improve the early diagnostic rate of RA. HCDU examination is a sensitive, secure, atraumatic and easily-operated diagnostic method for early RA patients with finger joint damage. When combined with anti-CCP antibody testing, it will provide a better chance for RA patients, and give them hope for a better treatment and improved prognosis.

Objectives Autophagy may represent a functional processing event that creates a substrate for autoreactivity. In particular, autophagy may play a role in the pathogenesis of RA, since autophagy is a key cellular event involved in the generation of citrullinated peptides, with consequent breakage of tolerance. Thus, in RA, autophagy may be the common feature in several situations (including smoking, joint injury and infection) that may drive the adaptive responses to citrullinated self-proteins. The aim of this study was the analysis, in vitro, of the role of autophagy in the generation of citrullinated peptides and, in vivo, of the relationship between autophagy and the production of anti-CCP antibodies (Abs). Methods For autophagy induction, fibroblast-like synoviocytes, primary fibroblasts and monocytes were stimulated with tunicamycin or rapamycin. Peptidyl arginine deiminase activity was tested by enzyme-linked immunosorbent assay, and protein citrullination was evaluated by western blotting. The main citrullinated RA candidate antigens, vimentin, α-enolase and filaggrin, were demonstrated by immunoprecipitation. The relationship between autophagy and anti-CCP Abs was analysed in 30 early-active RA patients. Results Our results demonstrated in vitro a role for autophagy in the citrullination process. Cells treated with tunicamycin or rapamycin showed peptidyl arginine deiminase 4 activation, with consequent protein citrullination. Immunoblotting and immunoprecipitation experiments, using specific Abs, identified the main citrullinated proteins: vimentin, α-enolase and filaggrin. In vivo, a significant association between levels of autophagy and anti-CCP Abs was observed in treatment-naive early-active RA patients. Conclusion These findings support the view that the processing of proteins in autophagy generates citrullinated peptides recognized by the immune system in RA.

Objective. To evaluate, firstly, all published data on baseline and annual progression rates of radiographic damage from all longitudinal observational cohorts, and secondly, the association of standard clinical and laboratory parameters with long-term radiographic joint damage. Methods. A comprehensive search of the literature from 1975 to 2014, using PubMed, SCOPUS and Cochrane databases, identified a total of 28 studies that investigated long-term radiographic progression, and 41 studies investigating predictors of long-term radiographic progression. This was submitted and approved by PROSPERO in February 2014 (Registration Number: CRD42014007589). Results. Meta-analysis indicated an overall baseline rate of 2.02%, and a yearly increase of 1.08% of maximum damage. Stratified analysis found that baseline radiographic scores did not differ significantly between cohorts recruiting patients pre- and post-1990 (2.01% vs 2.03%; P > 0.01); however, the annual rate of progression was significantly reduced in the post-1990 cohorts (0.68% vs 1.50%; P < 0.05). High levels of acute phase markers, baseline radiographic damage, anti-CCP and RF positivity remain consistently predictive of long-term radiographic joint damage. Conclusion. Critical changes in treatment practices over the last three decades are likely to explain the reduction in the long-term progression of structural joint damage. Acute phase markers and presence of RF/anti-CCP are strongly associated with increased radiographic progression.

Objective: The presence of anti-citrullinated protein antibodies (ACPAs) in primary Sjögren’s syndrome (pSS) ranges from 3% to 9.9%; however, there is no agreement about their clinical significance. Our aim was to systematically review the literature regarding the association of arthritis and ACPAs in pSS and their role in the development of rheumatoid arthritis (RA). Method: A comprehensive search of MEDLINE, ISI Web of Knowledge, and Cochrane Library from inception until June 2016 was undertaken using the combination of two or three of the keywords: primary Sjögren’s syndrome, Sjögren’s syndrome, arthritis, synovitis, arthropathy, anti-cyclic citrullinated peptide antibodies, and anti-citrullinated protein antibody–ACPA. No language restriction was used. Studies were included if they: assessed the association of arthritis and ACPAs, had sufficient data to construct a two-by-two table, tested immunoglobulin G ACPA by any method, and included patients with pSS according to a validated set of classification criteria. We used a random effects model and evaluated the heterogeneity and publication bias. Results: Ten studies were included (involving 1322 patients). We found a pooled odds ratio of 4.42 (95% confidence interval 1.15–16.94, p = 0.03). The test for heterogeneity was I 2 = 0.87. Publication bias was not observed. Based on data from three studies, 33 of 58 pSS patients with ACPAs (57%) developed RA compared with none of 598 pSS patients with negative ACPA (p and lt; 0.000001). Conclusion: Patients with pSS disclosing ACPAs are prone to arthritis as part of the clinical spectrum of the disease, but are also at risk of developing RA. © 2019, © 2019 Informa Healthcare on license from Scandinavian Rheumatology Research Foundation.

Objective To investigate the risk of progression to rheumatoid arthritis (RA) in patients who were cyclic citrullinated peptide (CCP) antibody positive without RA at initial presentation. Methods We performed a retrospective cohort study of CCP+ individuals seen at a US tertiary care system between 2009 and 2018 who were without RA or other systemic rheumatic disease by medical record review at the time of CCP antibody positivity. Progression to classifiable RA was determined through medical record review. We investigated the risk of progression to RA overall and stratified by CCP antibody level (low: >1 to 2× the upper limit of normal [ULN]; medium: >2 to 3× ULN; high: >3× ULN). Multivariable Cox regression estimated the hazard ratio (HR) and 95% confidence interval (95% CI) for RA by CCP antibody level. Results We identified 340 CCP+ patients who were without RA or other rheumatic disease at baseline. During 1,047 person-years of follow-up, 73 patients (21.5%) developed RA. The risk of progression to RA increased with CCP antibody level, with 46.0% (95% CI 34.7-55.3) of patients with high-level CCP antibodies progressing to RA by 5 years. Compared to low CCP antibody level, medium (HR 3.00 [95% CI 1.32-6.81]) and high (HR 4.83 [95% CI 2.51-9.31]) CCP antibody levels were strongly associated with progression to RA, adjusting for age, sex, body mass index, smoking, family history of RA, and rheumatoid factor level. Conclusion Among CCP+ patients without RA, the risk for progression to RA increased substantially with increasing CCP antibody level. This study provides further support for close monitoring for development of RA among CCP+ patients and identifying strategies to mitigate this risk.

It was with interest that we read the article by Belkhir et al 1 in the recent Annals of Rheumatic Disease . The article described the first report of rheumatoid arthritis (RA) and polymyalgia rheumatica developing after the use of immune checkpoint inhibitors to treat a variety of cancers. We found the article interesting and informative but noted that in all of their 10 reported cases, the patients seroconverted from rheumatoid factor (RF) or cyclic citrullinated peptide antibody (CCP) negative to positive, supporting their claim that ‘rheumatoid arthritis’ may develop after immune checkpoint inhibitor treatment. The report by Belkhir et al is in contrast to our experience managing …

Objective. The aim of this study was to investigate omega-3 fatty acid (FA) supplement use and omega-3 FAs in erythrocyte membranes [omega-3 FA % in erythrocyte membranes (RBC)] and their association with anti-CCP autoantibodies in a population without RA, but who are at genetic risk for RA. Methods. The multicentre Studies of the Etiology of RA (SERA) cohort includes RA-free subjects who are first-degree relatives of RA probands or are enriched with the HLA-DR4 allele. In a nested case-control study, 30 SERA cases were identified who were anti-CCP2 antibody positive. We further identified 47 autoantibody negative controls, frequency matched to cases on age at study visit, sex, race and study site. Anti-CCP2 status, self-reported omega-3 FA supplement use and omega-3 FA % in RBCs were obtained from a single visit. Results. Anti-CCP2 positive cases were less likely than controls to report omega-3 FA supplement use (odds ratio: 0.14; 95% CI 0.03, 0.68). In addition, the likelihood of anti-CCP2 positivity was inversely associated with total omega-3 FA % in RBCs (odds ratio: 0.47; 95% CI 0.24, 0.92, for a s.d. increase). Conclusion. The inverse association between anti-CCP2 positivity and self-reported omega-3 FA supplement use and omega-3 FA % in RBCs suggests that omega-3 FAs may protect against the development of RA-related autoimmunity in pre-clinical RA.

Introduction: Biological therapies have greatly improved the treatment efficacy in rheumatoid arthritis (RA). However, in clinical practice a significant proportion of patients experience an inadequate response to treatment. The aim of this study is to classify responding and non-responding rheumatoid arthritis patients treated with biological therapies, based on clinical parameters and symptoms used in Western and Chinese medicine. Methods: Cold and Heat symptoms accessed by a Chinese medicine (CM) questionnaire and Western clinical data were collected as baseline data, before initiating biological therapy. Categorical principal components analysis with forced classification (CATPCA-FC) approach was applied to the baseline data set to classify responders and non-responders. Results: In this study, 61 RA patients were characterized using a CM questionnaire and clinical measurements. The combination of baseline symptoms (‘preference for warm food’, ‘weak tendon severity’) and clinical parameters (positive rheumatoid factor/anti-cyclic citrullinated peptide antibody, C-reactive protein, creatinine) were able to differentiate responders from non-responders to biological therapies with a positive predictive value of 82.35% and a misclassification rate of 24.59%. Adding CM symptom variables in addition to clinical data did not improve the classification of responders, but it did show 8.3% improvement in classifying non-responders. Conclusions: No significant differences were found between the three classification models. Adding CM symptoms to the clinical parameters in the combined model improved the classification of non-responders. Although this improvement is not significant in the current study, we consider it worthwhile to further investigate the potential of adding symptom variables for improving treatment efficacy. © 2018 Elsevier GmbH Chemicals/CAS: abatacept, 332348-12-6; adalimumab, 331731-18-1; C reactive protein, 9007-41-4; certolizumab pegol, 428863-50-7; creatinine, 19230-81-0, 60-27-5; etanercept, 185243-69-0, 200013-86-1; golimumab, 476181-74-5; rheumatoid factor, 9009-79-4; rituximab, 174722-31-7; tocilizumab, 375823-41-9

Introduction: Biological therapies have greatly improved the treatment efficacy in rheumatoid arthritis (RA). However, in clinical practice a significant proportion of patients experience an inadequate response to treatment. The aim of this study is to classify responding and non-responding rheumatoid arthritis patients treated with biological therapies, based on clinical parameters and symptoms used in Western and Chinese medicine. Methods: Cold and Heat symptoms accessed by a Chinese medicine (CM) questionnaire and Western clinical data were collected as baseline data, before initiating biological therapy. Categorical principal components analysis with forced classification (CATPCA-FC) approach was applied to the baseline data set to classify responders and non-responders. Results: In this study, 61 RA patients were characterized using a CM questionnaire and clinical measurements. The combination of baseline symptoms (‘preference for warm food’, ‘weak tendon severity’) and clinical parameters (positive rheumatoid factor/anti-cyclic citrullinated peptide antibody, C-reactive protein, creatinine) were able to differentiate responders from non-responders to biological therapies with a positive predictive value of 82.35% and a misclassification rate of 24.59%. Adding CM symptom variables in addition to clinical data did not improve the classification of responders, but it did show 8.3% improvement in classifying non-responders. Conclusions: No significant differences were found between the three classification models. Adding CM symptoms to the clinical parameters in the combined model improved the classification of non-responders. Although this improvement is not significant in the current study, we consider it worthwhile to further investigate the potential of adding symptom variables for improving treatment efficacy. © 2018 Elsevier GmbH Chemicals/CAS: abatacept, 332348-12-6; adalimumab, 331731-18-1; C reactive protein, 9007-41-4; certolizumab pegol, 428863-50-7; creatinine, 19230-81-0, 60-27-5; etanercept, 185243-69-0, 200013-86-1; golimumab, 476181-74-5; rheumatoid factor, 9009-79-4; rituximab, 174722-31-7; tocilizumab, 375823-41-9

Objectives RA is an articular chronic inflammatory disease that in a subgroup of patients can also present with extra-articular manifestations (EAMs). Despite intense investigation on this topic, reliable biomarkers for EAMs are lacking. In recent years several ACPAs, including those targeting anti-citrullinated alpha enolase peptide-1 (anti-CEP-1), have been identified in patients with RA. Data about the ability of anti-CEP-1 to predict the development of erosive disease are confliciting and no evidence concerning their possible association with EAMs in RA is currently available. The aim of this study was to investigate the prevalence and significance of anti-CEP-1 with regard to the association with erosive disease and EAMs in a large cohort of patients with RA. Methods Anti-CCP and anti-CEP-1 antibodies have been assessed on serum samples of RA patients, healthy donors and patients with SpA using commercially available ELISA kits. Results Anti-CEP-1 antibodies are detectable in over 40% of RA patients and are associated with erosive RA and with RA-associated interstitial lung disease (ILD). Conclusion Anti-CEP-1 antibodies may represent a useful biomarker for RA-associated ILD and erosive disease to be employed in clinical practice.

Background: Interleukin (IL)-17 is the main Th-1 cytokine, produced by activated T-lymphocytes. The potential IL-17 value in rheumatoid arthritis (RA) pathogenesis consists of its independent inflammatory response induction and mediated stimulation of proinflammatory factors synthesis resulting in joint destruction. The aim of study was to determine the role of IL-17 in immuno-inflammatory/autoimmune reactions development and to reveal IL-17 serum level associations with clinical and immunological characteristics of RA. Methods: 50 patients with early RA (disease duration >, Russia), anti-CCP antibodies (Axies-Shield Diagnostic, UK) were revealed using ELISA immunoassay. Results: On the base of IL-17 serum level patients were divided in two groups: group1 (n = 28) were patients with normal IL-17 serum level and group2 (n = 22) were those with high IL-17 serum level. In the group2, the rate of patients' pain assessment by visual analogue scale (67.3 ± 7.2 vs 32.8 ± 4.6; P

Background Both Peptydil arginine deiminase of P. gingivalis (pPAD), and the human enzyme (hPAD), could citrullinarize peptides from the bacteria and human host in Rheumatoid Arthritis patients (RA). Chronic periodontitis (CP) could be associated with a constant generation of citrullinated proteins, and it lead to a proportional hPAD enzymatic production. Objectives The aim was to demonstrate the association between serum levels of hPAD4 and severe Periodontitis in patients with rheumatoid arthritis. Methods Patients with RA (n=127) matched with healthy controls (n=120) were studied in a cross-sectional study. Levels of human recombinant antigens for hPAD4; cyclic citrullinated peptide antibody (CCP3, IgG), Rheumatoid factor (IgM) and C-reactive protein (CRP); determined by ELISA test. The CP was classified according to the recommendations of the International Workshop for Classification of Periodontal Diseases and Conditions. Bivariate analysis to demonstrate the associations, and non-parametric analyzes were used according to the case. Results There were no significant demographic diffrences between the two groups. The median hPAD4 level was 1.21 (95% CI 1.4–1.7) in RA and 0.75 (95% CI 0.94–1.26) ng/ml in controls, (p The frequency of CP was higher in patients with RA than in controls (66.9 vs 43%, p A significant correlation was found between levels of hPAD4 with the DAS28 ESR score (p 2.0) correlated with hPAD4 levels (P Conclusions hPAD4 levels correlate with the severity of CP independent of the RA presence and in RA subjects with high score of disability and activity disease. The hPAD4 could be proposed as a serological marker of clinical severity in chronic diseases such as CP and RA. References Rose, H.M., C. Ragan, and et al., Differential agglutination of normal and sensitized sheep erythrocytes by sera of patients with rheumatoid arthritis. Proc Soc Exp Biol Med, 1948. 68(1): p. 1–6. Girbal-Neuhauser, E., et al., The epitopes targeted by the rheumatoid arthritis-associated antifilaggrin autoantibodies are posttranslationally generated on various sites of (pro)filaggrin by deimination of arginine residues. J Immunol, 1999. 162(1): p. 585–94. Lundberg, K., et al., Antibodies to citrullinated alpha-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase. Arthritis Rheum, 2008. 58(10): p. 3009–19. Mikuls, T.R., et al., Periodontitis and Porphyromonas gingivalis in patients with rheumatoid arthritis. Arthritis Rheumatol, 2014. 66(5): p. 1090–100. Disclosure of Interest None declared

Objective To analyze indirect immunofluorescence (IIF) patterns and autoantibodies identified by line immunoassay (LIA) in rheumatoid arthritis (RA) patients, and to compare the autoantibody profiles with serological markers to determine their relevance. Methods A total of 153 specimens were obtained from RA patients for diagnostic or monitoring purposes. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP) were measured, and autoantibody testing using IIF and LIA was performed. Frequencies of IIF patterns and autoantibodies identified by LIA were analyzed and compared with each other and with serologic markers of RF, including anti-CCP, ESR, and CRP. Results The overall positivity of IIF and LIA results was 49.7% and 34.0%, respectively. The most frequent IIF pattern in RA was homogenous (20.9%), followed by dense fine speckled (DFS) pattern (17%). Anti-SS-A and/or anti-Ro-52 were most frequently detected in RA irrespective of the observed IIF pattern. Positive rates and intensities of autoantibodies detected did not differ by therapeutic regimen or disease activity, as reflected by CRP levels or ESR. Only anti-CCP showed a tendency to increase depending on IIF intensity. Conclusions RA patients did not display a specific or dominant IIF pattern or autoantibody presence, as identified by LIA. RA patients had lower frequencies of anti-SS-A and anti-Ro-52 compared with other systemic autoimmune diseases (serologically characteristic of RA). IIF and LIA appear insufficient for diagnosing RA and monitoring disease activity yet can be useful for screening and differentiating major systemic autoimmune diseases. * RA : rheumatoid arthritis RF : rheumatoid factor anti-CCP : anti-cyclic citrullinated peptide APF : antiperinuclear factor AKA : antikeratin antibodies AFA : antifilaggrin antibodies ACR/EULAR : American College of Rheumatology/European League Against Rheumatism CRP : C-reactive protein ESR : erythrocyte sedimentation ratio IIF : indirect immunofluorescence LIA : line immunoassay ANA : antinuclear antibodies SPRA : seropositive rheumatoid arthritis ULN : upper limit of normal DFS : dense fine speckled DS : discrete speckled nRNP : nuclear ribonucleoprotein PCNA : proliferating cell nuclear antigen CENP-B : centromere protein B dsDNA : double-stranded DNA AMA-M2s : antimitochondrial antibodies ANOVA : analysis of variance LEDGF : lens epithelium-derived growth factor SLE : systemic lupus erythematosus SSC : systemic sclerosis NSAIDs : non-steroidal anti-inflammatory agents DMARD : disease modifying antirheumatic drugs ESR : erythrocyte sedimentation rate WBC : white blood cell nRNP/SM : nuclear ribonucleoprotein CENP-B : centromere protein B Scl-70 : topoisomerase I

Objectives: To determine factors influencing the age at onset of rheumatoid arthritis (RA). Methods: A sample of 152 Colombian patients was investigated. Hazard ratios (HRs) that measured the effect size of risk factors on the age at RA onset were computed by using Cox regression models. Results: Positive anti-CCP antibodies were associated with an increased risk of early RA onset (HR=1.60; 95% confidence interval, [1.06, 2.4]), whereas the presence of the protective 70DERAA74 sequence was associated with a delayed onset (HR=0.55; [0.33, 0.92]). After controlling for both anti-CCP antibodies and the 70DERAA74 sequence, the following variables did not influence significantly the age at RA onset: gender, ever cigarette smoking, family RA history, the TNF-308 A polymorphism, HLA shared epitope, and the presence of rheumatoid factor. Conclusion: Anti-CCP antibodies and the HLA-DRB1 70DERAA74 sequence influence the age at onset of RA. © 2010 Société française de rhumatologie.

Objectives. To evaluate the prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies and RF in RA patients and their relatives from Southern Brazil. Methods. Anti-CCP2 and IgM-RF were evaluated in 156 RA patients and 200 relatives. Sera from 100 healthy unrelated individuals were used as control. The anti-CCP2 was detected by ELISA and the IgM-RF using the latex agglutination test. Results. We identified 117 anti-CCP2 (75%)-positive and 106 RF (67.9%)-positive patients. Anti-CCP2 was increased in relatives (5.5%; 11/200) when compared with unrelated individuals (1%; P = 0.050). Titre of anti-CCP2 in RA patients did not differ from relatives [140.4 (75.7) vs 115.6 (84.2) U, respectively; P = 0.30]. Positive relatives were younger than patients for anti-CCP2 (P = 0.0081), RF (P < 0.001) and both concomitantly (P = 0.012), and although there was no difference for anti-CCP2 positivity according to gender, increased RF positivity and concomitant anti-CCP2/RF were observed in the female relatives (P = 0.067 and 0.082, respectively). No difference regarding the relative degree of tobacco use in relatives was detected. Among the 11 anti-CCP2-positive relatives, 2 females had RA diagnosis established and 6 individuals presented with joint symptoms suggestive of RA. Conclusion. The results demonstrate a significant positivity of anti-CCP2 in relatives of RA patients from Brazil and reinforce the importance of serological tools to identify undiagnosed RA.

Anti-cyclic citrullinated peptide antibodies (anti-CCP) are highly considered to indicate disease severity and be predictive markers in rheumatoid arthritis (RA). RA patients who are positive for anti-CCP tend to progress more frequently to joint deformity and functionally deteriorate more than negative patients. A study concerning the presence of anti-CCP in Japanese patients with psoriatic arthritis (PsA) has been published. Our aim was to clarify that anti-CCP could be a potentially useful marker in PsA patients. We herein describe a PsA patient with presence of anti-CCP. We examined anti-CCP in 15 patients with PsA, and compared with 18 controls who had other types of psoriasis. Three PsA patients were positive for anti-CCP, but no controls showed positive. The anti-CCP-positive patients had higher counts of radiographic erosion, higher prevalence rates of polyarticular disease, use of disease-modifying anti-rheumatic drugs, and the human leukocyte antigen DRB1*04 shared epitope than negative patients. Our study demonstrated that anti-CCP was potentially both predictive and a severity marker of joint involvement in PsA, the same as in RA.

The probability of one patient has ankylosing spondylitis (AS) and rheumatoid arthritis (RA) is low. It is usually difficult to diagnose the association, indeed we require a careful diagnostic process and more tests are needed. A 21-year-old female patient with coexisting AS and RA was reported here. 9 months later, she developed peripheral polyarthritis, erosion changes on the radiography of Metatarso-phalangeal (MTP), rheumatoid factor and cyclic citrullinated peptide antibody (anti-CCP) were positives. Here, we describe the diagnostic process that we followed.

Rheumatoid arthritis is both common and chronic, with significant consequences for multiple organ systems. Better understanding of its pathophysiology has led to the development of targeted therapies that have dramatically improved outcomes. The key to therapeutic success lies in identifying individuals who will have severe destructive disease as early as possible, so that effective treatment can be initiated before irreversible damage occurs. Anti-cyclic citrullinated peptide (anti-CCP) antibody testing is particularly useful in the diagnosis of rheumatoid arthritis, with high specificity, presence early in the disease process, and ability to identify patients who are likely to have severe disease and irreversible damage. However, its sensitivity is low, and a negative result does not exclude disease. Anti-CCP antibodies have not been found at a significant frequency in other diseases to date, and are more specific than rheumatoid factor for detecting rheumatoid arthritis. We discuss anti-CCP antibody testing in rheumatoid arthritis, with an emphasis on diagnostic performance, prognostic capability, and relevance to pathogenesis and new treatment paradigms in rheumatoid arthritis.

Background This review outlines current knowledge of diagnosis, assessment, treatment and risk factors for early rheumatoid arthritis (RA). Methods Selective review of current literature was obtained by searching the terms 'rheumatoid arthritis' and 'early'. Results Three issues dominate the current views on early RA. First, its recognition may be difficult. Many experts consider that early inflammatory arthritis should only be classified as RA after several months' of observation. Secondly, there is emphasis on early intensive treatment with conventional disease-modifying drugs or biologics, especially tumour necrosis factor inhibitors. Thirdly, there is a debate on the risk factors with evidence of genetic risks and environmental factors like smoking that may trigger RA. Developing citrullinated proteins followed by anti-cyclic citrullinated peptide antibodies, specific for RA, appears to be a crucial pathogenetic step. Discussion Early RA needs immediate specialist assessment and review. Early intensive therapy is effective but needs to be focussed on patients mostly at risk of severe progressive disease.

Objective: To explore the value of rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibody, C-reactive protein (CRP), and the erythrocyte sedimentation rate (ESR) in the diagnosis of rheumatoid arthritis (RA). Methods: Using rate nephelometry, chemiluminescence microparticle immunoassay (CMIA), and Westergren sedimentation rate testing, we detected RF, anti-CCP antibody, CRP, and ESR in 134 patients with RA and 50 healthy control individuals. Results: We observed significant differences in RF, anti-CCP antibody, CRP, and ESR concentrations between the RA and control groups ( P

Objective To evaluate antibodies against cyclic citrullinated peptide (anti-CCP antibodies) for their predictive value for severe joint destruction in rheumatoid arthritis (RA) and to examine their relationship to shared epitope (SE)-positive DRB1 alleles. Methods Concentrations of anti-CCP antibodies were determined in sera from 126 patients with recent onset RA who had been followed prospectively for 6 yr. Progression of joint destruction was evaluated according to Larsen by scoring radiographs from the hand and feet taken at baseline and after 1, 2, 4 and 6 yr of observation. In addition to clinical parameters, the presence of SE-positive DRB1 alleles and of rheumatoid factor IgM and IgA was determined. Results Anti-CCP antibodies were found more frequently and in higher concentrations in both DRB1*01-positive and in DRB1*04-positive SE-positive patients compared with SE-negative patients. Severe joint destruction as defined by a Larsen score in the upper third of the study population was predicted by positivity for anti-CCP antibodies, by the presence of SE-positive DRB1*04 alleles and by the presence of erosive disease at initial presentation. Multiple logistic regression analysis revealed that SE-positive DRB1*04 alleles and anti-CCP antibodies exerted a significant influence on the progression of joint destruction. Conclusion The association of anti-CCP antibodies with DRB1*01 and with SE-positive DRB1*04 alleles implies a functional role for the SE sequence motif. The determination of SE-positive DRB1*04 alleles and of anti-CCP antibody positivity facilitates the prediction of disease course and prognosis at the time of initial presentation.

Our aim is to assess the prevalence and associated clinical features of anti-CCP (cyclic citrullinated peptide) antibodies for RF (rheumatoid factor)-positive and RF-negative rheumatoid arthritis (RA) and psoriatic arthritis (PsA). In a prospective, cross-sectional, multi-centre study, we determined the titres of anti-CCP antibodies in 208 RA patients (129 RF-positive, 79 RF-negative), 56 PsA patients and 39 healthy controls (HC). Clinical parameters including disease activity (disease activity score 28-DAS28), physical disability (health assessment questionnaire-HAQ), functional capacity (functional class) and radiological erosions were investigated in patients with RA. In PsA patients, clinical and radiological features were determined. Anti-CCP2 antibodies were measured using a second-generation anti-CCP enzyme-linked immunosorbent assay (Euro-Diagnostica, Netherlands). One-hundred four of 129 RF-positive RA (81%), 16 of 79 RF-negative RA (20%), seven of 56 PsA patients (12.5%) and none of the HC had anti-CCP antibodies. RA patients with anti-CCP antibodies had significantly higher disease activity, greater loss of function and more frequent erosive disease than anti-CCP antibody-negative group. In subgroup analysis, anti-CCP antibodies in RF-negative patients were also associated with erosive disease. All PsA patients with anti-CCP antibodies had symmetric arthritis with higher number of swollen joints. The prevalence of anti-CCP antibodies in RF-positive RA patients was significantly higher than in RF-negative RA and PsA patients. Anti-CCP antibodies were also associated with erosive disease in RF-negative RA patients. Both anti-CCP and RF tests were negative in 30% of the patients. Anti-CCP positivity was a frequent finding in PsA and associated with symmetrical polyarthritis.

Objectives. Antibodies recognizing a cyclic citrullinated peptide (anti-CCP) are highly specific for rheumatoid arthritis (RA) but their role in psoriatic arthritis (PsA) remains unclear. The aim of this study was therefore to investigate the prevalence of anti-CCP antibodies in PsA and assess their clinical and genetic associations. Methods. One hundred and twenty-six patients with PsA, 40 patients with seropositive RA and 40 controls were tested for the presence of anti-CCP antibodies, rheumatoid factor (RF) and the HLA-DRB1 shared epitope. Clinical and radiological data were collected prospectively on all patients and compared between anti-CCP-positive and -negative patients. Results. Seven (5.6%) patients with PsA were positive for anti-CCP antibodies compared with 0% of controls and 97% of patients with seropositive RA. The presence of anti-CCP antibodies in PsA was significantly associated with the HLA-DRB1 shared epitope (P

Background: Antibodies that react with citrullinated proteins (anti-mutated citrullinated vimentin [anti-MCV] and second-generation anti-cyclic citrullinated peptide antibodies [anti-CCP2]) are markers for rheumatoid arthritis. Recent studies have demonstrated that these antibodies are present in other arthropathies including the spondyloarthritis, psoriatic arthritis, and juvenile idiopathic arthritis. Arthritis associated with inflammatory bowel disease (IBD) takes various forms, with some shared similarities with classic spondylarthropathies. Our objective was to investigate the role of anti-MCV and anti-CCP2 as potential biomarkers in IBD and related arthritis. Methods: In all, 125 IBD patients (71 males, 54 females) were compared to 81 age- and sex-matched healthy controls. Anti-MCV and Anti-CCP2 IgG were measured using an enzyme linked immunosorbent assay. Results: In the 125 IBD patients (mean age 32.6 ± 12.3 years), 44 (35.2%) had ulcerative colitis and 81 (64.8%) had Crohn's disease. Forty-four (35.2%) IBD patients developed arthritic manifestations. Antibody positivity was observed in 24/125 (19.2%) IBD patients and in 18/81 (22.2%) healthy subjects. The proportion of anti-MCV positivity among IBD patients and healthy individuals were similar: 16.8% vs. 16.0%, P = 0.887. Anti-CCP2 positivity among IBD patients and healthy individuals was also comparable: 6.4% vs. 6.2%, P = 0.948. Similarly, the presence of anti-MCV and anti-CCP2 antibodies was not different among IBD patients with and without arthritis. The mean titers of antibodies were low: anti-MCV (29.6 ± 7.5 U/mL) and anti-CCP2 (27.6 ± 4.0 U/mL) in IBD patients with arthritis. Conclusions: Autoantibodies to citrullinated proteins were low in IBD-related arthritis. These findings suggest that these antibodies are not useful biomarkers in IBD to predict who may develop IBD-related arthropathy. (Inflamm Bowel Dis 2012)

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Objective.Cyclic citrullinated peptide antibody (anti-CCP)-positive and anti-CCP-negative rheumatoid arthritis (RA) have been suggested as 2 distinctive disease subsets with respect to disease activity and prognosis. Previously, we proposed that anti-CCP antibodies might have a chondrocyte-suppressive effect. We aimed to compare circulating cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in untreated anti-CCP-positive and anti-CCP-negative RA, and to study the temporal pattern of COMP through 4 years of treatment, including the relationship to imaging and clinical findings.Methods.A total of 160 patients with newly diagnosed RA who were naive to disease-modifying antirheumatic drugs were included in the CIMESTRA trial. Ninety healthy blood donors served as controls. Demographic and disease measures including Disease Activity Score in 28 joints, IgM rheumatoid factor, anti-CCP, Health Assessment Questionnaire, visual analog scale scores for pain and global and physician assessment, and magnetic resonance imaging (MRI) of the nondominant hand were recorded at baseline. COMP in serum was measured by ELISA at inclusion and serially through 4 years.Results.Median baseline COMP was higher in patients with RA [9.8 U/l (interquartile range 8.96, 10.5)] compared with controls [8.3 U/l (IQR 7.84, 8.9); p < 0.001] and remained elevated at 4 years [10.8 U/l (IQR 10.2, 11.7); p < 0.001]. At baseline, anti-CCP-positive patients had lower COMP than anti-CCP-negative patients (p = 0.048). In anti-CCP-positive patients, COMP exhibited a parabolic course over 4 years, while COMP in anti-CCP-negative patients had an almost linear course. In anti-CCP-positive patients, COMP was associated with MRI edema and erosion score, while COMP was correlated with synovitis score in anti-CCP-negative individuals.Conclusion.Our study provides additional evidence for the existence of different disease pathways in anti-CCP-positive and anti-CCP-negative subsets of RA, and evidence that anti-CCP antibodies may be implicated in the disease process by modifying cartilage metabolism.

Chronic hepatitis C virus (HCV) has extrahepatic autoimmune properties and a variety of autoantibodies were found in patients with HCV. Patients with HCV infection may have rheumatic symptoms and signs, and 50-70% of the cases may contain rheumatoid factor (RF). The increased prevalence of RF in patients with HCV infection diminishes the diagnostic specificity of serum RF for rheumatoid arthritis (RA) in patients with HCV. Therefore, the presence of RF mostly does not help in distinguishing between RA and HCV-associated rheumatic symptoms. In this study, we studied whether cyclic citrullinated peptide (CCP) antibody, a highly specific biomarker for RA in the general population, was useful for the diagnosis of RA in nonarthritic patients with HCV (hepatitis C virus). Blood samples from 39 patients with chronic HCV infection, 87 normal sera from volunteer blood donors and 108 blood samples from patients with rheumatoid arthritis, from the rheumatology clinic, were taken. RF was measured using the Dade-Behring nephelometer and antibodies to CCP were measured with ELISA. According to statistical analysis, the sensitivity, specificity and positive predictive value of the anti-CCP test was superior to the RF test. Cyclic citrullinated peptide antibody is a more useful test than RF among patients with chronic HCV infection without arthritis.

IntroductionThe majority of autoimmune diseases such as rheumatoid arthritis (RA) and autoimmune thyroid diseases (AITDs) are characterized by a striking female predominance superimposed on a predisposing genetic background. The role of extremely skewed X-chromosome inactivation (XCI) has been questioned in the pathogenesis of several autoimmune diseases.MethodsWe examined XCI profiles of females affected with RA (n = 106), AITDs (n = 145) and age-matched healthy women (n = 257). XCI analysis was performed by enzymatic digestion of DNA with a methylation sensitive enzyme (HpaII) followed by PCR of a polymorphic CAG repeat in the androgen receptor (AR) gene. The XCI pattern was classified as skewed when 80% or more of the cells preferentially inactivated the same X-chromosome.ResultsSkewed XCI was observed in 26 of the 76 informative RA patients (34.2%), 26 of the 100 informative AITDs patients (26%), and 19 of the 170 informative controls (11.2%) (P < 0.0001; P = 0.0015, respectively). More importantly, extremely skewed XCI, defined as > 90% inactivation of one allele, was present in 17 RA patients (22.4%), 14 AITDs patients (14.0%), and in only seven controls (4.1%, P < 0.0001; P = 0.0034, respectively). Stratifying RA patients according to laboratory profiles (rheumatoid factor and anti-citrullinated protein antibodies), clinical manifestations (erosive disease and nodules) and the presence of others autoimmune diseases did not reveal any statistical significance (P > 0.05).ConclusionsThese results suggest a possible role for XCI mosaicism in the pathogenesis of RA and AITDs and may in part explain the female preponderance of these diseases.

Objective. To investigate the prevalence of anti-cyclic citrullinated peptide (anti-CCP) and anti-keratin antibodies (AKAs) in a cohort of patients with idiopathic inflammatory myopathy. Methods. In a cross-sectional study, we determined the presence of anti-CCP and AKAs by ELISA and IIF, respectively, in a cohort of 90 consecutive patients with idiopathic inflammatory myopathy. Associations between anti-CCP and clinical manifestations or other autoantibodies were determined with the chi-square and MannWhitney U-tests. Radiographs of hands were retrospectively evaluated. Serum autoantibody profile was determined in all patients. Results. Twelve patients were positive to anti-CCP (13.3); in eight cases values were moderatehigh. AKAs were not detected in any patient. Comparison between patients positive and negative to anti-CCP did not show clinical or biological differences. Arthritis joint erosions or positive status to anti-synthetase antibodies were not more frequent in patients with anti-CCP antibodies. Prevalence of RF was the only variable significantly associated with the presence of these antibodies (P0.043). Conclusions. High titres of anti-CCP can occasionally be found in patients with inflammatory myopathy. Therefore, a possible diagnosis of RA should be considered with caution in these patients.

The objective of this study was to examine the clinical and genetic variables associated with extra-articular rheumatoid arthritis (ExRA). This was a cross-sectional study in which 538 Northwestern Colombian patients with rheumatoid arthritis (RA) were included. Information about demographics and clinical characteristics including disease activity, inflammatory markers, co-morbidities, cardiovascular (CV) risk factors, history of familial autoimmunity and therapy was recorded. The presence of HLA 'shared epitope' (SE) alleles and TNF gene polymorphism was assessed. A multivariate statistical analysis was performed. ExRA was found in 32% of the patients, of which nodulosis, Sjögren's syndrome, and lung involvement were registered in 21%, 9%, and 4% of patients, respectively. Patients with ExRA were older than patients without it and they presented longer disease duration as well. Thus, an association between disease duration and ExRA manifestations was also observed. Patients with ExRA presented significant higher titers of anti-CCP antibodies as compared to patients without ExRA. Hypertension and thrombosis were significantly associated with ExRA. Never having smoked constituted a protective factor against ExRA onset. Associations between ExRA and the presence of traditional CV risk factors were also found. Our results show that duration of RA, CV disease and high titers of anti-CCP antibodies are associated with ExRA in Colombian patients with RA, and highlight the importance of preventing smoking in those who are prone to develop autoimmune diseases including RA. © Clinical Rheumatology 2009.

Annals of the Rheumatic Diseases, 71(11), pp.1916-1917; 2012

Objective Since modern treatment of rheumatoid arthritis (RA) is shifting toward aggressive antirheumatic therapy in an early phase of the disease, diagnostic tests with high specificity are desirable. A new serologic test (anti–cyclic citrullinated peptide [anti-CCP] enzyme-linked immunosorbent assay [ELISA]) was developed to determine the presence of antibodies directed toward citrullinated peptides, using a synthetic peptide designed for this purpose. Methods A cyclic peptide variant that contains deiminated arginine (citrulline) was designed and used as antigenic substrate in ELISA. Test parameters and diagnostic characteristics of the test were studied in patients with and without RA, in patients with various infectious diseases, and in a group of patients from an early arthritis clinic (EAC). Results Using prevalent RA and non-RA sera, the anti-CCP ELISA proved to be extremely specific (98%), with a reasonable sensitivity (68%). Also, in the EAC study group, the anti-CCP ELISA appeared to be highly specific for RA (96%). In comparison with the IgM rheumatoid factor (IgM-RF) ELISA, the anti-CCP ELISA had a significantly higher specificity (96% for CCP versus 91% for IgM-RF; P = 0.016) at optimal cut-off values. The sensitivity of both tests for RA was moderate: 48% and 54% for the anti-CCP ELISA and the IgM-RF ELISA, respectively (P = 0.36). Combination of the anti-CCP and the IgM-RF ELISAs resulted in a significantly higher positive predictive value of 91% (P = 0.013) and a slightly lower negative predictive value of 78% (P = 0.35) as compared with the use of the IgM-RF ELISA alone. The ability of the 2 tests performed at the first visit to predict erosive disease at 2 years of followup in RA patients was comparable (positive predictive value 91%). Conclusion The anti-CCP ELISA might be very useful for diagnostic and therapeutic strategies in RA of recent onset.

Background Rheumatoid factor (RF) positivity that may occur in a number of patients with HBV infection poses challenges in terms of differential diagnosis with rheumatoid arthritis (RA). On the other hand, antibodies to cyclic citrullinated peptide (anti-CCP) may prove to be an important marker for differential diagnosis of the two conditions. Objectives This study aimed to assess anti-CCP and RF positivity among patients with hepatitis B and rheumatoid arthritis. Methods Anti-CCP and RF seropositivity was assessed in 61 patients with HBV infection (32 patients with chronic hepatitis, 29 patients with inactive HBV carrier status), and 40 patients with RA as the control group. Results RF positivity was found in 18.7% and 34.4% of the patients with chronic hepatitis B and inactive HBV carrier status, respectively. On the other hand, only one patient with chronic hepatitis B had low positive anti-CCP. RF was positive in 24 (60%) and anti-CCP was positive in 26 (65%) patients among the 40 patients with RA. Conclusions Anti-CCP may be helpful in the differential diagnosis between RA and chronic hepatitis B infection or inactive HBV carrier status. References Inanc N, Dalkilic E, Kamali S, et al. (2007) Anti-CCP antibodies in rheumatoid arthritis and psoriatic arthritis. Clin Rheumatol 26, 17-23. Lee SI, Yoo WH, Yun HJ, et al. (2007) Absence of antibody to cyclic citrullinated peptide in sera of non-arthritic patients with chronic hepatitis B virus infection. Clin Rheumatol 26, 1079-82. Lienesch D, Morris R, Metzger A, Debuys P, Sherman K (2005) Absence of cyclic citrullinated peptide antibody in nonarthritic patients with chronic hepatitis C infection. J Rheumatol 32, 489-93. Disclosure of Interest None Declared

In their well-done meta-analysis, Nishimura and colleagues confirm that autoantibodies against cyclic citrullinated peptide (CCP) are more specific than rheumatoid factor for diagnosis of rheumatoi...

Rheumatoid factor (RF) and autoantibodies against cyclic citrullinated peptide (CCP) are markers that might help physicians diagnose rheumatoid arthritis.To determine whether anti-CCP antibody more accurately identifies patients with rheumatoid arthritis and better predicts radiographic progression than does RF.MEDLINE through September 2006 and reference lists of retrieved studies and review articles.Studies in any language that enrolled at least 10 participants and that examined the role of anti-CCP antibody and RF in the diagnosis or prognosis of known or suspected rheumatoid arthritis.Two authors independently evaluated studies for inclusion, rated methodological quality, and abstracted relevant data.The DerSimonian-Laird random-effects method was used to summarize sensitivities, specificities, and positive and negative likelihood ratios from 37 studies of anti-CCP antibody and 50 studies of RF. The pooled sensitivity, specificity, and positive and negative likelihood ratios for anti-CCP antibody were 67% (95% CI, 62% to 72%), 95% (CI, 94% to 97%), 12.46 (CI, 9.72 to 15.98), and 0.36 (CI, 0.31 to 0.42), respectively. For IgM RF, the values were 69% (CI, 65% to 73%), 85% (CI, 82% to 88%), 4.86 (CI, 3.95 to 5.97), and 0.38 (CI, 0.33 to 0.44). Likelihood ratios among IgM RF, IgG RF, and IgA RF seemed to be similar. Results from studies of patients with early rheumatoid arthritis were similar to those from all studies. Three of 4 studies found that risk for radiographic progression was greater with anti-CCP antibody positivity than with IgM RF positivity.Many studies had methodological limitations. Studies of RF were heterogeneous and had wide ranges of sensitivity and specificity.Anti-CCP antibodies are more specific than RF for diagnosing rheumatoid arthritis and may better predict erosivedisease.

OBJECTIVES: To compare the sensitivity and specificity of serum anti-Cyclic Citrullinated Peptideantibody (anti-CCP) with serum rheumatoid factor in diagnosing rheumatoid arthritis (RA) in acommunity hospital in Lahore, Pakistan.DESIGN: Cross-sectional analytical study.PLACE & DURATION OF STUDY: Subjects were recruited from Fatima Memorial Hospital,Rheumatology Outpatient Department from January, 2010 to December, 2010. The research work wasconducted at Department of Physiology and Cell Biology of University of Health Sciences, Lahore.SUBJECTS & METHODS: Eighty diagnosed patients of rheumatoid arthritis and thirty normalhealthy controls were included in the study. After selection of subjects, written informed consent wasobtained. The venous blood sample was taken and secured in vacutainers. Serum was extracted bycentrifugation and stored at -20°C till analysis. Titers of anti-CCP and rheumatoid factor weredetermined by ELISA. The data obtained was analyzed by using SPSS version 16.0.RESULTS: The sensitivity and specificity of serum anti-CCP was found to be 58.6% and 86.7%respectively as compared to 47.5% and 83.3% for serum rheumatoid factor (RF) in diagnosingrheumatoid arthritis. Sensitivity of anti-CCP antibody in RF negative sub-group was 32.1%.CONCLUSION: Serum anti-CCP antibody is more sensitive and specific marker for diagnosis ofrheumatoid arthritis as compared to the rheumatoid factor.KEY WORDS: Rheumatoid Arthritis, Anti- Cyclic Citrullinated Peptide Antibody (ACCP), Rheumatoid Factor