Anti-citrullinated Peptide Research Articles

The severity of the articular deformities of the hands depending on the seropositivity in rheumatoid arthritis

Abstract Background. Rheumatoid arthritis (RA), met in the literature also as chronic evolving polyarthritis, is a chronic inflammatory disease, which typically involves the small and medium joints, with a symmetric distribution. Clinical studies shown that a proportion of patients with RA, without measurable rheumatoid factors are a distinct entity from those patients with seropositive RA. Around one third of patients with RA are seronegative for those two serological markers, the rheumatoid factors (RF) and anti-citrullinated peptide antibodies (Anti-CCP). Hands are the most frequently affected in both seropositive and seronegative RA and the first joints involved in the inflammatory process are the metacarpo-phalangeal joints, IFP joints and the radiocarpian joint. The big joints become later symptomatic, after the small joints are affected. Materials and methods: 66 patients files and the personal records of the patients consecutively admitted in the Rheumatology Department of the Clinical Emergency County Hospital Constanta. Patients from county Constanta were included in the study, with diagnosis of rheumatoid arthritis (diagnosis confirmed at least 2 years ago), including both forms (seropositive and seronegative) of the disease. The complete clinical exam was done for the patients included in the study, following the identification of the active joint disease. The mechanical status of the joint was observed by a single evaluator for each of those 66 patients with RA, with special focus on the presence of the deformities / ankyloses of the hands joints. Therefore, there were evaluated: the mobility (the number of the joints with limited movements), deformities, ankyloses (the number of the joints without mobility). The joint mobility was assessed by counting the hand joints with limited movements and the worsening of the prehension function. The presence of the following hand deformities was followed: fingers in “swan neck”, “fusiform fingers”, the thumb “in Z”, and the aspect of “hand in the shape of a camel back”. For evaluating the painful or swollen joints we used: the 28 joint index, the overall evaluation of the disease activity - by the patient (Patient Global Assessment-PGA) and by the doctor (Medical Doctor Global Assessment- MDGA), the score of disease activity DAS 28 (DAS28 - Disease Activity Score 28), the index of the clinical activity of the disease (Clinical Disease Activity Index- CDAI), as well as the simplified index of activity of the disease (Simplified Disease Activity Index-SDAI). It was determined for each patient the plasma RF and anticitrullinated peptide antibodies. Results and discussion. As expected, there is a bigger frequency of female patients in both forms of the disease (seropositive and seronegative) and regarding males the recurrence is approximate equal between those two groups. By comparing the frequency of the joint deformities at hand level between the 2 groups of patients included in the study (seropositive PR and seronegative PR), we saw a superiority of these (with all their forms) in the patients with seropositive polyarthritis. Conclusions. The clinical study done in this work is completing the data offered by the studies of some dedicated authors, who analysed the characteristic elements of rheumatoid arthritis depending on seropositivity. Our results confirm the idea that seronegative rheumatoid arthritis has a more gentle clinical evolution and is a less destructive form of disease.

Anti-citrullinated peptides antibodies in systemic sclerosis: Meta-analysis of frequency and meaning

ObjectivesDiagnosis of systemic sclerosis (SSc) is partially determined by the presence of specific autoantibodies often associated with specific clinical features. Recent studies report the presence of ACPA in SSc. We aimed to evaluate the prevalence of ACPA in SSc and to assess their influence on clinical presentation of SSc. MethodsA systematic literature search was performed using PubMed and Cochrane databases’ publications between 1999 and March 2017. Search terms were: “systemic sclerosis [MeSH] AND (ACPA OR anti-CCP OR rheumatoid factor OR cohort OR value diagnostic)”. In a first step, we selected cohorts with >50 SSc patients with ACPA identification, for ACPA frequency determination. In a second step, we included studies that analysed clinical profiles according to ACPA status. Meta-analyses were performed when at least two studies were available. ResultsFirst, we identified 13 observational studies with a total of 1231 SSc patients. The mean prevalence of ACPA in SSc was 9.2%. Secondly, we identified nine studies reporting clinical aspects according to ACPA status. Our meta-analyses showed a significant association between ACPA positivity and the presence of arthritis (odds ratio (OR)=22.48 [10.71–47.21]), joint erosions seen on X-rays (OR=14.79 [6.38–34.28]), pulmonary fibrosis (OR=2.75 [1.21–6.24]), oesophagus involvement (OR=2.72 [1.05–7.07]), and diffuse skin involvement (OR=2.21 [1.21–4.03]). ConclusionsThe prevalence of ACPA in scleroderma is 9.2%. Our meta-analysis shows an increased risk for erosive arthritis, pulmonary fibrosis, oesophagus involvement and diffuse skin involvement, in patients with ACPA-positive SSc. ACPA should be systematically included in SSc assessment.

Synovial Immunophenotype and Anti-Citrullinated Peptide Antibodies in Rheumatoid Arthritis Patients: Relationship to Treatment Response and Radiologic Prognosis.

Serum anti-citrullinated peptide antibodies (ACPAs) may be present before the development of rheumatoid arthritis (RA) and may be predictive of more severe, erosive disease. This study was undertaken to examine the synovial tissue immunophenotype according to ACPA status in patients with RA, as well as the response to treatment and erosion status. Consecutive RA patients were prospectively recruited and underwent clinical and serologic assessments before and after treatment. Radiologic assessment was performed at the time of clinical follow-up. Synovial tissue was immunostained for specific markers of B cells (CD19), T cells (CD3, CD4, and CD8), macrophages (CD68), and blood vessels (factor VIII). Serum CXCL13 levels were quantified by enzyme-linked immunosorbent assay. Synovial tissue sections were analyzed for immunophenotype according to ACPA status, using a validated semiquantitative scoring method, and also analyzed for the presence of lymphoid aggregates. Response to treatment with nonbiologic or biologic disease-modifying antirheumatic drugs was assessed using the European League Against Rheumatism (EULAR) response criteria. In total, 123 subjects (78 ACPA+) were included. Compared to ACPA- RA patients, synovium from ACPA+ RA patients was characterized by significantly higher levels of CD19+ B cells and CD3+ and CD8+ T cells (each P < 0.05), and CD19+ B cell levels were significantly higher in patients who were naive to treatment. The CD19+ B cell infiltrate level was higher in patients with erosions at follow-up (P = 0.0128). Levels of lymphoid aggregates of CD19+ B cells were significantly higher in ACPA+ patients (P < 0.05), and this was associated with increased serum CXCL13 levels. The EULAR response was significantly associated with the level of CD3+ T cell infiltrates (P < 0.05), while CD68+ macrophage and CD8+ T cell levels were predictive of the response to tumor necrosis factor inhibitors (P < 0.05). The results of this prospective study demonstrate that the levels of synovial B cell infiltrates and lymphoid aggregates were significantly higher in ACPA+ RA patients, especially those who were naive to treatment. In addition, ACPA+ subjects developed more erosions during progression of the disease and had higher serum levels of CXCL13. The EULAR response to therapy in ACPA+ RA patients was associated with increased levels of T cell and macrophage markers.

Practical Approach to the Evaluation and Management of Rheumatoid Arthritis-Interstitial Lung Disease Based on its Proven and Hypothetical Mechanisms.

The prevalence of interstitial lung disease in patients with rheumatoid arthritis varies from 10 to 42%. Rheumatoid arthritis patients with interstitial lung disease have three times the risk of death compared with those without the disease. Prognosis seems to be related to the high-resolution computed tomography pattern. Usual interstitial pneumonia pattern, resembling idiopathic pulmonary fibrosis, carries a worse prognosis. Validated strategies to identify different phenotypes and assess the disease activity in rheumatoid arthritis interstitial lung disease are lacking. However, the utilization of high-resolution computed tomography, composed disease activity scores, and anti-citrullinated peptide antibodies titers can help to guide decisions in clinical practice. Mechanisms involved in lung disease may be different from those implicated in joint involvement. This could explain why in a significant proportion of cases, interstitial lung disease does not improve or even worsens with standard therapies used successfully to treat the joint component (e.g. anti- umor necrosis factor agents). In this scenario, a group of drugs that targets the adaptive immune response (e.g. rituximab or abatacept) seems to target more specifically the process that takes place in the lungs. Moreover, the recent emergence of anti-fibrotic drugs, which have already proven effective in idiopathic pulmonary fibrosis, may provide an alternative treatment strategy in rheumatoid arthritis-usual interstitial pneumonia. In this review, we propose a practical approach to the evaluation and therapy of rheumatoid arthritis interstitial lung disease. Validation of strategies directed to assess the activity of lung disease and identify the underlying mechanisms are needed. Clinical trials evaluating a therapeutic approach with specific targets based on the disease phenotype are warranted.

Early Diagnosing and Treatment of Rheumatoid Arthritis, Benefits of Anti-Citrullinated Peptides Examination

Abstract Background: Anti-citrullinated peptides antibodies (ACPA) are specific for rheumatoid arthritis and have been implicated in disease pathogenesis. ACPA examination is a new component of ACR/EULAR 2010 classification criteria for rheumatoid arthritis. ACPA positivity predicts a more erosive disease course with severe joint damage and extra-articular manifestations. Objectives: To evaluate the benefits of ACPA examination in patients with early undifferentiated arthritis and patients with rheumatoid arthritis. Methods: We examined patients with arthritis and tested them for ACPA positivity. In every individual patient we evaluated if ACPA examination was necessary to establish the diagnosis of rheumatoid arthritis, or to change treatment, or if the diagnosis could have been established without ACPA examination (ACR/EULAR 2010 classification criteria was met without ACPA scoring). Results and Conclusions: We examined 833 patients with arthritis. There were 43 patients, or 62 % of a subgroup of 69 who were ACPA positive whose ACPA examination was not needed - ACR/EULAR criteria was met without ACPA scoring. This number represents 5.1 % of the total number examined. There were 15 patients, or 22 % of the subgroup and 1.8 % of the total whose diagnosis was revised to rheumatoid arthritis due to ACPA positivity - ACR/EULAR criteria was met solely with ACPA scoring. There were 11 patients (16 % and 1.3 %) whose medication was changed due to ACPA positivity. ACPA examination is useful in 3,1 % of all examined patients. When we correlate data on ACPA positive patients, 38 % of the patients profit from ACPA examinations. Considering the relatively low price of ACPA testing, this examination should not be excluded.

Local bone loss in patients with anti-citrullinated peptide antibody and arthralgia, evaluated with high-resolution peripheral quantitative computed tomography

Objective: To investigate bone changes in the metacarpophalangeal (MCP) joints of anti-citrullinated peptide antibody (ACPA)-positive patients with arthralgia, but not arthritis, compared to healthy controls.Method: Using a cross-sectional study design, patients were recruited from hospitals and private care rheumatologists, and controls from a test subject website. All subjects underwent medical history interview, clinical examination, and biochemical screening including ACPA. Patients with positive ACPA, arthralgia, and no rheumatic disease were included. Controls without a history or signs of rheumatological disease or positive ACPA were included. A 2.7-cm-long region around the second and third MCP joints was evaluated using high-resolution peripheral quantitative computed tomography with a voxel size of 82 µm.Results: Twenty-nine ACPA-positive patients and 29 healthy controls were evaluated. Trabecular volumetric bone mineral density and bone volume fraction did not differ between the groups. In addition, the cortical bone was not affected in patients, as we found no difference in average cortical thickness and cortical bone area between the groups. In contrast, the trabeculae were significantly (p < 0.05) thinner in both second and third MCP heads compared with controls, whereas trabecular number and trabecular separation did not differ between the groups. No erosions were demonstrated and the number of non-specific breaks did not differ between the groups.Conclusion: Trabecular bone changes were observed in ACPA-positive patients with arthralgia compared with healthy controls. The results may reflect inflammatory up-regulated trabecular bone resorption leading to early bone loss before the onset of clinical arthritis.

Calprotectin as a marker of inflammation in patients with early rheumatoid arthritis

ObjectivesCalprotectin is an inflammatory marker of interest in rheumatoid arthritis (RA). We evaluated whether the level of calprotectin was associated with disease activity, and if it was predictive of treatment...

Is Male Rheumatoid Arthritis an Occupational Disease? A Review.

Background:Rheumatoid arthritis (RA) is a systemic, inflammatory disease with an estimated global prevalence of 0.3–1.0%. An unexplained association exists between low formal education and the development of RA independent of smoking. It is established that RA is initiated in the lungs and that various occupations associated with dust, fume and metal inhalation can increase the risk of RA development.Objective:The objective of this review is to evaluate published clinical reports related to occupations associated with RA development. We highlight the concept of a “double-hit” phenomenon involving adsorption of toxic metals from cigarette smoke by dust residing in the lung as a result of various work exposures. We discuss the relevant pathophysiological consequences of these inhalational exposures in relation to RA associated autoantibody production.Method:A thorough literature search was performed using available databases including Pubmed, Embase, and Cochrane database to cover all relative reports, using combinations of keywords: rheumatoid arthritis, rheumatoid factor, anti-citrullinated peptide antibody silica, dust, fumes, metals, cadmium, cigarette smoking, asbestos, mining, bronchial associated lymphoid tissue, heat shock protein 70, and adsorption.Conclusion:We postulate that the inhalation of dust, metals and fumes is a significant trigger factor for RA development in male patients and that male RA should be considered an occupational disease. To the best of our knowledge, this is the first review of occupations as a risk factor for RA in relation to the potential underlying pathophysiology.

Chikungunya virus and autoimmunity.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus. Fever, rash and severe arthralgia are the hallmarks of chikungunya fever (CHIKF), the disease caused by this virus. The acute course of the disease usually lasts few weeks to months. Chronic, relapsing or persistent arthralgia and arthritis have been described mimicking rheumatoid arthritis (RA), requiring immunosuppressive drugs.The purpose of this review is to characterize both the chronic clinical course of CHIKF-associated arthritis and the immunological pathogenic mechanisms involved. The effect of postepidemic chronic persistent rheumatic course on the functional status of affected individuals, affecting large populations, has been studied. One-third of affected individuals had persistent pain months to years postepidemic and the identified risk factors for functional disability were identified.Inflammatory biomarkers associated with disease severity of RA such as interleukin 6 (IL6), and relevant chemokines have been found to correlate with the severity of postepidemic chronic disease. There are conflicting reports on antinuclear antibodies (ANAs) as well as rheumatoid factor and anti-citrullinated peptide antibody (ACPA) sero-positivity during infections.According to a recent study, eight out of 10 infected individuals developed chronic persistent rheumatic course and met classification criteria for seronegative RA.In a flow cytology analyses, these eight patients, similar to a group of RA patients, had a greater percentage of activated and effector CD4 and CD8 T cells than healthy controls. Patients with CHKV infections may have a chronic persistent course of musculoskeletal disease, overlapping clinical and immunologic features with RA patients. In the appropriate setting and awareness, CHIKV infection should be considered when a patient is evaluated with a new symmetric polyarthritis.The question to be raised: Is it possible that in genetic prone individuals and in a particular environmental and infectious setting, such as CHIKF outbreak, an autoimmune disease will emerge?

Anti-citrullinated peptide antibodies are the strongest predictor of clinically relevant radiographic progression in rheumatoid arthritis patients achieving remission or low disease activity: A post hoc analysis of a nationwide cohort in Japan.

ObjectivesTo determine prognostic factors of clinically relevant radiographic progression (CRRP) in patients with rheumatoid arthritis (RA) achieving remission or low disease activity (LDA) in clinical practice.MethodsUsing data from a nationwide, multicenter, prospective study in Japan, we evaluated 198 biological disease-modifying antirheumatic drug (bDMARD)-naïve RA patients who were in remission or had LDA at study entry after being treated with conventional synthetic DMARDs (csDMARDs). CRRP was defined as the yearly progression of modified total Sharp score (mTSS) >3.0 U. We performed a multiple logistic regression analysis to explore the factors to predict CRRP at 1 year. We used receiver operating characteristic (ROC) curve to estimate the performance of relevant variables for predicting CRRP.ResultsThe mean Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) was 2.32 ± 0.58 at study entry. During the 1-year observation, remission or LDA persisted in 72% of the patients. CRRP was observed in 7.6% of the patients. The multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: anti-citrullinated peptide antibodies (ACPA) positivity at baseline (OR = 15.2, 95%CI 2.64–299), time-integrated DAS28-ESR during the 1 year post-baseline (7.85-unit increase, OR = 1.83, 95%CI 1.03–3.45), and the mTSS at baseline (13-unit increase, OR = 1.22, 95%CI 1.06–1.42).ConclusionsACPA positivity was the strongest independent predictor of CRRP in patients with RA in remission or LDA. Physicians should recognize ACPA as a poor-prognosis factor regarding the radiographic outcome of RA, even among patients showing a clinically favorable response to DMARDs.

Regulatory B cells in rheumatoid arthritis: Alterations in patients receiving anti-TNF therapy

Cytokines, including tumor necrosis factor alpha (TNFα) are involved in Rheumatoid arthritis (RA) pathogenesis by augmenting autoimmunity, sustaining long term inflammation in the synovium, and promoting joint damage. Anti-TNF therapy is one of the most efficient and widely used therapies for RA, although its mechanism is not clarified yet. Earlier we demonstrated that RA patients have a reduced number of IL-10 producing regulatory B cells (B10 cells) as compared to healthy individuals and they are functionally impaired. Our aim was to study the influence of anti-TNF therapy on B10 cells in RA, to follow the alteration of B cell activation markers (CD25, CD69) and to monitor the level of citrullinated peptid-specific antibodies and the secreted IL-10 in patients' sera during the therapy.We have observed that at six month after starting the therapy the frequency of B10 cells remarkably increased, while the expression of the activation marker, CD69 decreased on B cells. In contrast, serum levels of IL-10 and anti-citrullinated peptide antibodies did not change post-treatment. ConclusionThe reduced activation state of B cells and the increasing number of regulatory B10.cells might contribute to the therapeutic efficacy of anti-TNF agents in RA.

DNA methylation mediates genotype and smoking interaction in the development of anti-citrullinated peptide antibody-positive rheumatoid arthritis

BackgroundMultiple factors, including interactions between genetic and environmental risks, are important in susceptibility to rheumatoid arthritis (RA). However, the underlying mechanism is not fully understood. This study was undertaken to evaluate whether DNA methylation can mediate the interaction between genotype and smoking in the development of anti-citrullinated peptide antibody (ACPA)-positive RA.MethodsWe investigated the gene-smoking interactions in DNA methylation using 393 individuals from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA). The interaction between rs6933349 and smoking in the risk of developing ACPA-positive RA was further evaluated in a larger portion of the EIRA (1119 controls and 944 ACPA-positive patients with RA), and in the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) (1556 controls and 792 ACPA-positive patients with RA). Finally, mediation analysis was performed to investigate whether DNA methylation of cg21325723 mediates this gene-environment interaction on the risk of developing of ACPA-positive RA.ResultsWe identified and replicated one significant gene-environment interaction between rs6933349 and smoking in DNA methylation of cg21325723. This gene-smoking interaction is a novel interaction in the risk of developing ACPA-positive in both Caucasian (multiplicative P value = 0.056; additive P value = 0.016) and Asian populations (multiplicative P value = 0.035; additive P value = 0.00027), and it is mediated through DNA methylation of cg21325723.ConclusionsWe showed that DNA methylation of cg21325723 can mediate the gene-environment interaction between rs6933349 and smoking, impacting the risk of developing ACPA-positive RA, thus being a potential regulator that integrates both internal genetic and external environmental risk factors.

Transcriptional profiling of leukocytes from rheumatoid arthritis patients before and after anti-tumor necrosis factor therapy: A comparison of anti-nuclear antibody positive and negative subsets.

Anti-nuclear antibodies (ANAs) may be induced in patients with rheumatoid arthritis (RA) receiving anti-tumor necrosis factor (TNF) therapy with TNF inhibitors (TNFi), etanercept, infliximab or adalimumab. In the present study, 11 patients who were TNFi drug naive were started on TNFi at a time of high disease activity. Of these, all cases were positive for rheumatoid factor and 9 cases tested were positive for anti-citrullinated peptide (anti-CCP) antibodies prior to TNFi treatment. Peripheral blood mononuclear cells (PBMCs) and serum were collected from all patients before and after TNFi therapy. Serum was assayed for ANAs over time. Total cellular RNA was extracted from PBMCs and assessed using Illumina arrays. Gene expression profiles were examined for alterations in key effector pathways. After 3 or more months on TNFi, 6 patients converted to ANA-positivity. Analysis of transcripts from patients with RA who converted to ANA-positivity after 3 months on TNFi identified complex gene expression profiles that reflected a reduction in cell adhesion, cell stress and lipid metabolism transcripts. In summary, unique transcriptional profiles in PBMCs from patients with RA were observed after TNFi therapy. This pilot study suggests that transcriptional profiling is a precise method of measuring the impact of TNFi therapies and reveals novel pathways that likely influence the immune response.

Anti-Citrullinated Cyclic Peptide Antibody and Functional Disability Are Associated With Poor Sleep Quality in Rheumatoid Arthritis.

This study aims to determine the predictors of poor sleep quality in rheumatoid arthritis (RA). This was a monocentric, cross sectional, case-control study which was conducted at the Putrajaya Hospital, Malaysia. We recruited 46 patients with RA (3 males; 43 females; mean age 48.15±14.96) and 46 age and sex-matched healthy controls (3 males; 43 females; mean age 47.11±12.22). RA patients were assessed for their disease activity based on disease activity score in 28 joints, disease damage based on radiographic erosions, and functional status based on Health Assessment Questionnaire Disability Index. The Pittsburgh Sleep Quality Index (PSQI) scores were determined by interviewing all the subjects. Subjects with RA were further subdivided based on their PSQI scores as "good sleepers" with PSQI scores of <5 and "poor sleepers" with PSQI scores of ≥5. The percentage of poor sleepers was significantly higher among RA patients (47.83% versus 9.57%). Median scores of 5 out of 7 components of the PSQI were higher among RA patients compared to controls. Among poor sleepers with RA, a significantly higher proportion tested positive for anti-citrullinated cyclic peptide autoantibodies (p=0.037). Besides, poor sleepers had significantly higher median Health Assessment Questionnaire Disability Index (p=0.017) than good sleepers. However, both Health Assessment Questionnaire Disability Index (p=0.968) and anti-citrullinated cyclic peptide (p=0.431) were insignificant when entered in the equation of a logistic regression model. The findings of this study demonstrate a link between functional disability, anti-citrullinated cyclic peptide antibodies, and sleep quality in RA.

Artritis reumatoide

ConceptRheumatoid arthritis is a systemic inflammatory disease of immune etiopathogenesis. EpidemiologyPresence of persistent synovitis in the joints. The pattern of joint involvement is usually symmetrical and erosive and can develop at any age. EtiopathogenesisIt is unknown, repeated exposure to certain environmental agents (tobacco and citrullination) has been related as a possible harmful mechanism, associated to a genetic predisposition to an immune response. Clinical manifestationsPatients present swelling of the joints, and polyarticular clinical forms usually appear, with multiple clinical involvement and progress patterns. Other extra-articular manifestations can develop, such as skin diseases, rheumatoid nodules, or pleuropulmonary or hematological manifestations. DiagnosisIt is conducted upon the presence of arthritis in association with radiographic and analytical data such as a positive rheumatoid factor and/or anti-citrullinated peptide antibodies. TreatmentThe course of the disease is poor if left untreated. Early treatment prevents structural progression. Some patients respond to traditional therapies with DMARDs (mostly methotrexate) and avoid further damage, but in many cases biological drugs are required, such as anti-TNF/anti-interleukin, or even anti-CD20, that have played an undisputed role in this disease.

Longitudinal study of clinical prognostic factors in patients with early rheumatoid arthritis: the PREDICT study.

To assess the association between baseline clinical prognostic factors and subsequent Disease Activity Score of 28 joints (DAS28) remission in early rheumatoid arthritis (RA). Data were collected using point of care clinical software from participating rheumatology centres. Patients aged 18 years or over whose date of clinical onset of RA was within the previous 12-24 months, who had at least 6 months of follow-up data and a DAS28-ESR (erythrocyte sedimentation rate) score recorded between 12 and 24 months from first being seen for RA were included. Data collected included baseline demographics, mode of disease onset, pattern of joint involvement at onset, smoking status, DAS28, rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPA), time from symptom onset to presentation and disease activity at baseline. Univariate and multivariate logistic regression of DAS28-ESR remission between 12 and 24 months after first assessment were performed. Data from 1017 patients were analyzed: 70% female; mean age 60 years (SD: 14.7); 70% RF-positive, 58% ACPA-positive. The strongest age and sex adjusted baseline predictors of DAS28-ESR remission at 12-24 months were remission at baseline (odds ratio [OR]: 4.49, 95% CI: 2.17-9.29, P < 0.001), being male (OR: 2.42, 95% CI: 1.46-4.01, P < 0.001), abstaining from alcohol (P < 0.001) and being lower weight (OR: 0.98, 95% CI: 0.97-1.00, P = 0.015). There was no statistically significant association between joint onset patterns, mode of onset, RF, ACPA or smoking status. In this observational study, patients with early RA at risk of not achieving remission include those with high disease activity at baseline, women, those who drink alcohol and those with higher body weight.

Carbamylation of vimentin is inducible by smoking and represents an independent autoantigen in rheumatoid arthritis

ObjectivesSmoking has been connected to citrullination of antigens and formation of anti-citrullinated peptide antibodies (ACPAs) in rheumatoid arthritis (RA). Since smoking can modify proteins by carbamylation (formation of homocitrulline), this...

Rheumatoid Nodules and Lung

Among the pulmonary manifestations of rheumatoid arthritis (RA), rheumatoid nodules (RN) are frequent even if mostly asymptomatic. They are generally peripheral and different for sizes (up to 8 centimeter in diameter) and number (one or more). RN can be a consequence of RA or of the drugs used for RA. In the first case, they usually appear in patients with more aggressive and seropositive longstanding RA and are often associated with cutaneous RN. Methotrexate, leflunomide, azathioprine among the disease-modifying anti-rheumatic drugs (DMARDS) and etanercept among “biological” ones are the more frequent responsible drugs. RN induced by drugs are histologically identical to non-drugsinduced RN. In these cases, drug withdrawal is the first therapeutic choice. Differential diagnosis with other causes of pulmonary nodule is imperative, especially when RN is the first clinical manifestation of RA and serum levels of rheumatoid factor (RF) and/or anti-citrullinated peptides antigens (ACPA) are in the normal ranges. Cancer (primitive or metastatic) and infectious diseases represent the main diagnostic dilemma. The exclusion of neoplastic or infectious causes is particularly important in the course of immunosuppressive therapy for RA. As highlighted by some authors, bronchogenic carcinoma can grow on RN and RN can be associated with metastatic nodules or infectious nodules in the lung, but these are outstanding events. Percutaneous biopsy or thoracotomy remain the gold standard for diagnosis especially when high-resolution computed tomography (HRCT) or positron emission tomography (PET) -CT features and laboratory tests are not conclusive. Keywords: Caplan's syndrome, diagnostic algorithm, differential diagnosis, drug-toxicity, pulmonary involvement, rheumatoid arthritis, rheumatoid nodules.

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)

Association of anti-citrullinated protein or peptide antibodies with left ventricular structure and function in rheumatoid arthritis.

High levels of ACPAs in RA are associated with more severe arthritis and worse prognosis. However, the role of ACPAs in mediating the increased risk of heart failure in RA remains undefined. We examined whether specific ACPAs were associated with subclinical left ventricular (LV) phenotypes that presage heart failure. Sera from RA patients without clinical cardiovascular disease were assayed for specific ACPAs using a custom Bio-Plex bead assay, and their cross-sectional associations with cardiac magnetic resonance-derived LV measures were evaluated. High ACPA level was defined as ⩾ 75th percentile. Findings were assessed in a second independent RA cohort with an expanded panel of ACPAs and LV measures assessed by 3D-echocardiography. In cohort 1 (n = 76), higher levels of anti-citrullinated fibrinogen 41-60 and anti-citrullinated vimentin antibodies were associated with a 10 and 6% higher adjusted mean LV mass index (LVMI), respectively, compared with lower antibody levels (P < 0.05). In contrast, higher levels of anti-citrullinated biglycan 247-266 were associated with a 13% lower adjusted mean LVMI compared with lower levels (P < 0.001). In cohort 2 (n = 74), the association between ACPAs targeting citrullinated fibrinogen and citrullinated vimentin peptides or protein and LVMI was confirmed: higher anti-citrullinated fibrinogen 556-575 and anti-citrullinated vimentin 58-77 antibody levels were associated with a higher adjusted mean LVMI (19 and 15%, respectively; P < 0.05), but no association with biglycan was found. Higher levels of antibodies targeting citrullinated fibrinogen and vimentin peptides or protein were associated with a higher mean LVMI in both RA cohorts, potentially implicating autoimmune targeting of citrullinated proteins in myocardial remodelling in RA.