Anti-citrullinated Peptide Antibodies Research Articles

Consideration of differences in drug usage between young-onset and elderly-onset rheumatoid arthritis with target of low disease activity

Objectives Elderly-onset rheumatoid arthritis (EORA) is reported to differ from young-onset rheumatoid arthritis (YORA) with regard to patient background and drug treatment. We examined the amount of drug administered to patients who achieved low disease activity (LDA) for rheumatoid arthritis at our hospital. Methods Demographics, clinical history, and treatments were compared between patients with EORA (n = 70) and YORA (n = 190). Results There was a significant difference in the average age (73.8 vs. 57.8 years), disease duration (6.66 vs. 14.7 years), and sex (62.9% males vs. 83.7% females), but no difference in rheumatoid factor positivity (85.3% vs. 80.7%), anti-citrullinated peptide antibody positivity (86.5% vs. 87.7%), simplified disease activity index (4.28 vs. 4.59), or disease activity score 28-CRP (1.99 vs. 2.04) in the EORA and YORA groups, respectively. There were also no significant differences in prednisolone use (37.1% vs. 36.3%), amount of methotrexate administered (MTX) (1.45 vs. 1.41 mg), and MTX use (55.7% vs. 65.3%). However, the MTX dose (2.89 vs. 4.09 mg/week, p = .011) and overall biologics use (32.9% vs. 56.3%, p = .0012) were significantly lower in patients with EORA than in those with YORA. Conclusion Patients with EORA may be able to achieve LDA with lower drug dosage than those with YORA.

Elevated Peripheral T Helper Cells Are Associated With Atrial Fibrillation in Patients With Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) have a significantly high risk of atrial fibrillation (AF). This study aimed to compare the absolute and relative changes in peripheral T cells in patients with RA who were also affected with and without AF. To help make an early diagnosis and prevent the initiation and progression of AF, the changes in the lymphocyte subsets were assessed in RA patients with and without AF. A propensity score matching (PSM) system (1:3) was used to perform a matched case-control study with 40 RA-AF cases and 120 RA controls. Changes in the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-citrullinated peptide antibody (ACPA), and rheumatoid factor (RF) were examined. The percentage and absolute number of T, B, natural killer (NK), T helper (Th)1, Th2, Th17, and T-regulatory (Treg) cells in the peripheral blood of patients with and without RA-AF were determined using flow cytometry. Univariate and multivariate analyses were performed to determine the association between peripheral lymphocytes and RA-AF. Demographic data, ESR, CRP, ACPA, and the percentage, as well as the absolute value of B, NK, Th2, and Treg cells, showed no significant differences between the propensity score-matched groups of RA and RA-AF. Meanwhile, the absolute number and percentage of Th1 cells, the absolute number of Th17 cells, the ratio of Th1/Treg, Th17/Treg, and RF were significantly higher in patients with RA-AF than those in the control groups (P < 0.05). Univariate and multivariate logistic regression analyses also revealed that the percentage of Th1 cells, the absolute number of Th17 cells, and the ratio of Th1/Treg were associated with a significantly higher risk of AF. This PSM study demonstrated that the incidence of AF was higher in RA patients with Th cell immunological derangements.

The Role of Skeletal Radiology and the Limits of Serologic Assays in Distinguishing among the Causes of Inflammatory Arthritis

Current classification criteria utilize different serological findings, such as anti-citrullinated-peptide antibodies (ACPA) and rheumatoid factor (RF), as well as clinical findings, for diagnosis of rheumatoid arthritis (RA). The presence of erosions allows diagnosis, even if serological criteria are not fulfilled. However, the pertinent erosions are not clearly defined.

Identification of a Novel Serological Marker in Seronegative Rheumatoid Arthritis Using the Peptide Library Approach.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation mainly affecting the joints leading to cartilage and bone destruction. The definition of seropositive or seronegative RA is based on the presence or absence of rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPAs). Other autoantibodies have been identified in the last decade such as antibodies directed against carbamylated antigens, peptidyl-arginine deiminase type 4 and v-Raf murine sarcoma viral oncogene homologue B. In order to identify relevant autoantigens, we screened a random peptide library (RPL) with pooled IgGs obtained from 50 patients with seronegative RA. Patients’ sera were then used in an ELISA test to identify the most frequently recognized peptide among those obtained by screening the RPL. Sera from age- and sex-matched healthy subjects were used as controls. We identified a specific peptide (RA-peptide) recognized by RA patients’ sera, but not by healthy subjects or by patients with other immune-mediated diseases. The majority of sera from seronegative and seropositive RA patients (73.8% and 63.6% respectively) contained IgG antibodies directed against the RA-peptide. Interestingly, this peptide shares homology with some self-antigens, such as Protein-tyrosine kinase 2 beta, B cell scaffold protein, Liprin-alfa1 and Cytotoxic T lymphocyte protein 4. Affinity purified anti-RA-peptide antibodies were able to cross react with these autoantigens. In conclusion, we identified a peptide that is recognized by seropositive and, most importantly, by seronegative RA patients’ sera, but not by healthy subjects, conferring to this epitope a high degree of specificity. This peptide shares also homology with other autoantigens which can be recognized by autoantibodies present in seronegative RA sera. These newly identified autoantibodies, although present also in a percentage of seropositive RA patients, may be considered as novel serum biomarkers for seronegative RA, which lacks the presence of RF and/or ACPAs.

Epidemiology and clinical characteristics of systemic sclerosis overlap syndrome (SSc-OS), and the factors significantly associated with SSc-OS in Thai patients with systemic sclerosis.

To investigate the epidemiology and characteristics of systemic sclerosis (SSc) overlap syndrome (SSc-OS). This study included patients enrolled in the Siriraj Systemic Sclerosis Cohort registry during November 2013 to September 2019. SSc-OS was defined as SSc patients who also met criteria for rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), dermatomyositis (DM), polymyositis (PM), Sjogren, and/or antiphospholipid antibody syndrome. Baseline and 1-year characteristics were compared between SSc and SSc-OS. 185 patients (age 50.3 ± 11.4 years, 85.4% female, disease duration 2.7 years, 75.1% diffuse cutaneous subset, 75.6% anti-Scl-70 positivity) were included. The incidence and prevalence rate of SSc-OS was 3.2/100 patient-years and 17.8%. Regarding SSc-OS, 12.4%, 2.2%, 1.1%, 1.6%, and 0.5% of patients were classified as SSc-RA, SSc-SLE, SSc-PM, SSc-RA-SLE, and SSc-SLE-PM. SSc-OS had a higher prevalence of limited cutaneous subset (lcSSc), usual interstitial pneumonia, finger contractures, ESR >20 mm/hr., globulin >3.5 g/dL, rheumatoid factor, anti-citrullinated peptide antibody, and antiphospholipid antibodies. LcSSc subset (OR: 11.3, 95%CI: 2.0-62.6) and globulin >3.5 g/dL (OR: 6.2, 95%CI: 1.6-23.6) were associated with SSc-OS. SSc-OS is associated with the lcSSc subset. RA is the most common overlap syndrome. LcSSc patients with globulin >3.5 g/dL are associated with SSc-OS.

Factores asociados con fracturas vertebrales asintomáticas en pacientes con artritis reumatoide en un servicio de reumatología de Bogotá (Colombia)

IntroductionIn patients with rheumatoid arthritis (RA), osteoporotic vertebral fractures (VOF) are of multifactorial aetiology. The main mechanism is spontaneous and therefore most are asymptomatic. The presence of VF has an impact on the quality of life of patients, and consequently on morbidity and mortality, therefore it should be systematically evaluated in this population, especially when associated factors have been reported. ObjectivesThe main objective of this study was to identify clinical characteristics for osteoporosis and poor prognosis in rheumatoid arthritis that could be associated with the development of osteoporotic vertebral fractures identified in the lateral chest X-ray of asymptomatic patients with RA. The secondary objectives were to present the frequency, location, and severity of the fractures, as well as the inter and intra-observer correlation, when analysing the radiographs. MethodologyPatients with a diagnosis of RA were included, with a lateral chest X-ray and indication dissimilar to spinal symptoms. The mean age was 58 years (IQR 21-88). Three researchers evaluated 151 images in a sequenced and standardized manner using the Algorithm-Base Qualitative approach (ABQ) and Genant methods. Variables associated with the presence of osteoporosis and poor prognosis in RA were identified. Subsequently, a multivariate analysis was carried out to find an association with the presence of VF in this population. ResultsWe found 39 fractures in 32/151 patients. Identifying multiple fractures in 5 of them. The prevalence of osteoporotic vertebral fractures was 21.2%. The distribution of fractures was mainly at the level of T5, T8 and T9, with a predominance of Genant grade 1 in 46%. In the multivariate analysis, age, duration of RA (mainly greater than 10 years), rheumatoid factor, anti-citrullinated peptide antibodies, DAS28, HAQ, presence of antinuclear antibodies (ANA), smoking and being under treatment for osteoporosis showed a statistically significant association. The interobserver correlation for the ABQ and Genant methods presented a kappa index of.9 and.92, respectively. ConclusionIn patients with RA there is a significant association with the development of VF, independent of the presence of osteoporosis. Furthermore, this research suggests that the presence of some clinical and paraclinical characteristics could be associated with the prevalence of osteoporotic vertebral fractures. Age, duration of arthritis, poor prognostic markers for RA in terms of serology and functionality, as well as being in treatment for osteoporosis had statistical significance of association. This should guide the timely detection of fractures, independent of symptoms, with the respective targeted treatment in this population and thus avoid functional complications and a decrease in quality of life.

Increased plasma levels of CCL20 in peripheral blood of rheumatoid arthritis patients and its association with clinical and laboratory parameters.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that primarily affects small joints. The impaired chemokine and cytokine responses are essential pathological mechanisms for the RA clinical presentation. Given the role of chemokines and inflammatory reactions in RA pathogenesis, we evaluate the association between the plasma concentration of CCL20 with the clinical and laboratory parameters in newly diagnosed RA patients. Forty-five newly diagnosed RA patients and forty-five healthy subjects were enrolled in this study. The plasma levels of CCL20, rheumatoid factor, and anti-citrullinated peptide antibodies were measured using the enzyme-linked immunosorbent assay (ELISA) technique. The plasma levels of CCL20 were increased significantly in RA patients compared to the healthy controls (p < 0.0001). There was a positive correlation between CCL20 and RF, anti-CCP, ESR, and DAS-28 (p < 0.0001, r = 0.669; p < 0.015, r = 0.358; p < 0.0001, r = 0.586; p < 0.0001, r = 0.769). The increased plasma levels of CCL20 in newly diagnosed RA patients may contribute to RA pathogenesis, and it is in association with clinical and laboratory parameters. Key Points • CCL20 has a contribution to the early phase of RA.

A fructosylated peptide derived from a collagen II T cell epitope for long-term treatment of arthritis (FIA-CIA) in mice

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease which affects primarily the joints. Peptides of several proteins have shown an effect in some experimental animal models of RA. We investigated arthritis development in male DBA/1 mice which were injected with bovine collagen II (bCII) and human fibrinogen (hFib) on days 0 and 21, leading to stable and reproducible disease induction in 100% of immunized mice (FIA-CIA). In a second study, two bCII—derived peptides were given three times in the course of 6 weeks after FIA-CIA induction to test for impact on arthritis. Mice were scored weekly for arthritis and anti-citrullinated peptide antibodies (ACPAs) were determined in the sera taken on days 0, 14, 35, 56 and 84. Histology of the hind paws was performed at the end of the experiment. Intravenous administration of peptide 90578, a novel fructosylated peptide derived from the immunodominant T cell epitope of bCII, at a dosage of 1 mg/kg resulted in significant beneficial effects on clinical outcome parameters and on the arthritis histology scores which was sustained over 12 weeks. Survival tended to be improved in peptide 90578-treated mice. Intravenous administration of pure soluble peptide 90578 without adjuvants is a promising approach to treat RA, with treatment starting at a time when ACPAs are already present. The results complement existing data on peptide “vaccination” of healthy animals, or on treatment using recombinant peptide expressing virus or complex biological compounds.

Clinical Relevance of Autoantibodies and Inflammatory Parameters in Non-infectious Scleritis

ABSTRACT Purpose Scleritis is a potentially blinding disorder, with highly unpredictable course and outcome. We analyzed the prevalence and clinical relevance of autoantibodies and inflammatory parameters in non-infectious scleritis. Methods Retrospective analysis of laboratory findings in all consecutive patients at the department of Ophthalmology of the Erasmus MC with non-infectious scleritis. Results We included 81 patients with non-infectious scleritis. A systemic autoimmune disease was present in 46%. Positive anti-nuclear antibodies were found in 30%, anti-neutrophil cytoplasmic antibodies were positive in 19%, and the presence of rheumatoid factor was shown in 17%. The aforementioned autoantibodies, as well as inflammatory parameters, failed to show prognostic clinical value. In contrast, anti-citrullinated peptide antibodies (ACPA), found in 9% of scleritis patients, were significantly associated with the development of scleral necrosis (P = .01). Conclusions The presence of ACPA in patients with non-infectious scleritis was associated with the development of scleral necrosis.

Single-cell sequencing of immune cells from anticitrullinated peptide antibody positive and negative rheumatoid arthritis

The presence or absence of anti-citrullinated peptide antibodies (ACPA) and associated disparities in patients with rheumatoid arthritis (RA) implies disease heterogeneity with unknown diverse immunopathological mechanisms. Here we profile CD45+ hematopoietic cells from peripheral blood or synovial tissues from both ACPA+ and ACPA- RA patients by single-cell RNA sequencing and identify subsets of immune cells that contribute to the pathogenesis of RA subtypes. We find several synovial immune cell abnormalities, including up-regulation of CCL13, CCL18 and MMP3 in myeloid cell subsets of ACPA- RA compared with ACPA+ RA. Also evident is a lack of HLA-DRB5 expression and lower expression of cytotoxic and exhaustion related genes in the synovial tissues of patients with ACPA- RA. Furthermore, the HLA-DR15 haplotype (DRB1/DRB5) conveys an increased risk of developing active disease in ACPA+ RA in a large cohort of patients with treatment-naive RA. Immunohistochemical staining shows increased infiltration of CCL13 and CCL18-expressing immune cells in synovial tissues of ACPA- RA. Collectively, our data provide evidence of the differential involvement of cellular and molecular pathways involved in the pathogenesis of seropositive and seronegative RA subtypes and reveal the importance of precision therapy based on ACPA status.

Rheumatoid arthritis in a sickle cell patient: a dangerous association?

Introduction - The diagnosis of rheumatoid arthritis remains a challenge because sickle cell disease can result in various rheumatological manifestations, including joint and bone pain. The concomitant presence of rheumatoid arthritis and sickle cell disease makes the therapeutic management of both conditions problematic.&#x0D; Observation - A 24-year-old man, a nurse by profession, has been followed for 10 years for homozygous sickle cell disease at the Sickle Cell Disease Research Center (CRLD) of Bamako, Mali. He has presented for 8 months symmetrical polyarthritis with morning stiffness of 3 hours, distinct from the usual vaso-occlusive crisis. The Analog Visual Scale was estimated at 80/100. He reported unquantified weight loss and asthenia. The physical examination showed a deformity in bilateral ulnar deviation, flexion of the right elbow, twelve painful joints, and five swollen joints. Normochromic normocytic anemia (hemoglobin 8.3g/dl), inflammatory syndrome with C - Reactive Protein (CRP) 130.91 mg, and Sedimentation Rate (ESR) 72mm at the first hour were noted. Rheumatoid Factor was weakly positive at 21.3 IU and Anti Citrullinated Peptide Antibodies at 385.2 IU. The radiography discovered bilateral erosive carpets without associated tarsitis and osteonecrosis of both femoral heads. The diagnosis of a very active immunopositive erosive rheumatoid arthritis meeting the criteria of ACR / EULAR 2010 was retained. A treatment based on prednisone 10 mg per day was initiated, associated with methotrexate at a dosage of 15 mg weekly in single-dose, folic acid, calcium, and vitamin D.&#x0D; Conclusion - The coexistence of rheumatoid arthritis in sickle cell patients makes the diagnosis of polyarthritis difficult.

Genetic Factors of Predisposition and Clinical Characteristics of Rheumatoid Arthritis in Russian Patients.

Rheumatoid arthritis (RA) is a multifactorial disease caused by a genetic predisposition and environmental factors. Predisposing alleles of various genes have a relatively small influence on the disease risk when they appear separately, but in combination, they predispose an individual to RA development. We genotyped 125 patients with RA including 60 SNPs and sequenced coding part of six genes by next-generation sequencing (NGS) technology on a target panel (IAD177464_185). According to our data, the alleles HLA-DRB1*04, HLA-DRB1*01, HLA-B*27, PTPN22 (rs2476601), TNF (rs1800629), TPMT (rs2842934), and IL4 (rs2243250), and genotypes HLA-DRB1*04:04, HLA-DRB1*01:16, PTPN22 (rs2476601), TPMT (rs2842934), were significantly associated with the RA development. Associations with clinical criteria (DAS28-CRP, HAQ-DI, and CDAI) and biochemical factors were investigated. We have shown that the PADI4 genotypes (rs11203367, rs2240340, rs11203366, and rs874881) are significantly associated with the baseline levels of DAS28-CRP, HAQ-DI, and CDAI; genotypes IL23R (rs7530511) and TNFRSF1A (rs748004, rs2228144) with the level of anti citrullinated peptide antibodies (ACPA); the genotypes DHODH (rs3213422) and MTHFR (rs180113) with the concentration of C-reactive protein (CRP); and the genotypes IL2RA (rs2104286), IRAK3 (rs11541076), and IL4R (rs1801275) with the level of rheumatoid factor (RF). Application of targeted NGS panel contributes to expanded genotyping to identify risk groups among the RA patients.

POS0538 RELATIONSHIP BETWEEN HINDFOOT DEFORMITIES AND ULTRASOUND TENOSYNOVITIS IN RHEUMATOID ARTHRITIS

Background:Rheumatoid arthritis (RA) is an inflammatory disease that frequently affects the joints and soft tissues of the feet. Tibialis posterior tenosynovitis has a reported prevalence between 13 and 64% in RA. The condition is associated with a progressive flat foot deformity and significant gait disability. However, few studies have investigated the relationship between foot deformities and the involvement of tendons. Recently, ultrasonography (US) has been reported as the gold standard for the investigation of tendons.Objectives:This study aimed to assess the relationship between hindfoot deformities and US tenosynovitis in RA.Methods:We conducted a cross-sectional study including patients with RA (ACR/EULAR 2010). Demographic data and disease parameters were collected. For each patient, a podoscope examination of both feet was performed by a rheumatologist. A radiologist experienced in musculoskeletal imaging performed a US examination using a Philips HD11 device with a high-frequency linear transducer. The assessed lesions were synovitis of the tibiotalar, talonavicular, and subtalar joints, and tenosynovitis of tibialis anterior (TA), extensor hallucis longus (EHL), extensor digitorum longus (EDL), tibialis posterior (TP), flexor digitorum longus (FDL), flexor hallucis longus (FHL), fibularis brevis (FB) and fibularis longus (FL) tendons. The presence or absence of synovitis and tenosynovitis was recorded, and the composite synovitis score (power doppler/grayscale ultrasound (PDUS)) was measured for each joint. The US score of each patient was defined by the sum of the composite scores of the joints studied (0-30). A p-value &lt;0.05 was considered significant.Results:Sixty-two feet were examined in 31 RA patients (25 women and six men) with a mean age of 54.8±10.8 years old [32-70]. The mean disease duration was 8.5±7.2 years [1-37]. Rheumatoid Factor (RF) and Anti-Citrullinated Peptides Antibodies (ACPA) were positive in respectively 61.3% and 83.8% of cases. The mean DAS28 ESR was 3.8±1.5 [0.6-7].Podoscope examination revealed pes planus valgus (PPV) in 55.6% of cases and pes cavus varus (PCV) in 18.5% of cases. US showed tibiotalar synovitis in 59.3% of cases, talonavicular synovitis in 64.8% of cases, and subtalar synovitis in 46.3% of cases. In the anterior compartment, tenosynovitis of TA was noted in 5.6% of cases, of EHL in 1.9% of cases, and EDL in 9.3% of cases. In the medial compartment, tenosynovitis of TP was found in 22.2% of cases, of FDL in 5.6% of cases, and FHL in 0% of cases. In the lateral compartment, tenosynovitis of FB and FL was found in 25% and 11.1% of cases respectively.An association between PPV and synovitis of the tibiotalar joint (p&lt;0.001) and the subtalar joint (p=0.007) was found. An association was also noted with FL tenosynovitis (p=0.045) but not with the other assessed tendons.No association was noted between PCV and synovitis or tenosynovitis of the assessed structures.Conclusion:PPV was frequent among RA patients. This condition was associated with tibiotalar and subtalar synovitis and FL tenosynovitis. It is important to detect and correct foot deformities in order to ensure optimal control of the disease.Disclosure of Interests:None declared

Current favourable 10-year outcome of patients with early rheumatoid arthritis: data from the ESPOIR cohort.

To report the 10-year outcome of an inception cohort of patients with early rheumatoid arthritis (RA), the ESPOIR cohort, and predictors of outcome. From 2003 to 2005, 813 patients were included if they had early arthritis (<6 months) with a high probability of RA and had never been prescribed DMARDs. Multivariate analysis was used to evaluate predictors of outcome. In total, 521 (64.1%) RA patients were followed up for 10 years; 35 (4.3%) died, which appears to be similar to the French general population. Overall, 480 (92.1%) patients received a DMARD; 174 (33.4%) received at least one biologic DMARD, 13.6% within 2 years. At year 10, 273 (52.4%) patients were in DAS28 remission, 40.1% in sustained remission, 14.1% in drug-free remission, 39.7% in CDAI remission. Half of the patients achieved a health assessment questionnaire-disability index (HAQ-DI) < 0.5. SF-36 physical component and pain were well controlled. Structural progression was weak, with a mean change from baseline in modified Sharp score of 11.0 (17.9). Only 34 (6.5%) patients required major joint surgery. A substantial number of patients showed new comorbidities over 10 years. Positivity for anti-citrullinated peptides antibodies (ACPA) was confirmed as a robust predictor of long-term outcome. We report a very mild 10-year outcome of a large cohort of patients with early RA diagnosed in the early 2000s, which was much better than results for a previous cohort of patients who were recruited in 1993. This current favourable outcome may be related to more intensive care for real-life patients.

Artritis reumatoide

Rheumatoid arthritis (RA) is a chronic inflammatory disease of autoimmune origin that affects the joints, damaging bone and cartilage. In addition, because it is chronic, it generates significant direct and indirect costs, both for the individual and for society. These costs include disability, work productivity losses and reduced quality of life. Universally distributed and of unknown aetiology, RA affects 1% of the population. The pathogenesis of RA, partially unknown, has been linked with repeated exposure to environmental factors such as tobacco and to protein citrullination, associated with a genetic predisposition to develop an immune response. Patients present symmetrical multi-joint swelling with inflammatory pain and morning stiffness. However, there are different clinical patterns of the onset, evolution and impact of RA. Patients can also develop extra-articular clinical features such as rheumatoid nodules, pulmonary, haematological or neurological involvement and other associated comorbidities. The criteria used depend on classifications. Patients are diagnosed based on the presence of arthritis, along with typical laboratory and radiology data such as rheumatoid factor and anti-citrullinated peptide antibodies.

The impact of autoantibodies against citrullinated, carbamylated, and acetylated peptides on radiographic progression in patients with new-onset rheumatoid arthritis: an observational cohort study.

A range of anti-modified protein antibodies (AMPAs) are associated with rheumatoid arthritis. We aimed to assess the relationship between AMPA profiles and radiographic progression in patients with new-onset rheumatoid arthritis. In this cohort study, we obtained samples and data from the Scottish Early Rheumatoid Arthritis (SERA) inception cohort and biobank, which recruited patients with new-onset rheumatoid arthritis or undifferentiated arthritis who had at least one swollen joint from 20 hospitals across Scotland. AMPAs in plasma samples were measured by ELISAs at baseline. Paired radiographs of the hands and feet were taken at baseline and at 1 year and were scored with the Sharp-van der Heijde (SvH) method. We calculated differences in radiographic progression using estimated marginal mean changes between baseline and 1 year, with the baseline values of radiographic variables, rheumatoid factor, sex, age at recruitment, symptom duration, and Disease Activity Score 28 with C-reactive protein included as covariates. Between March 1, 2011, and April, 30, 2015, 1073 patients were recruited to the SERA study. 362 patients with rheumatoid arthritis were included in our study and had their AMPA profiles determined. Patients were grouped into four main autoantibody profiles by reactivities to post-translational modifications: single positivity for anti-citrullinated peptide antibodies (ACPAs; 73 [20%]); double positivity for ACPAs and anti-acetylated peptide antibodies (AAPAs; 45 [12%]); triple positivity for ACPAs, AAPAs, and anti-carbamylated peptide antibodies (151 [42%]); and AMPA negativity (74 [20%]). 19 (5%) patients were in one of the minor autoantibody groups. Of the 233 patients with both antibody data and radiographs of sufficient quality, triple-positive patients had more radiographic progression between baseline and 12 months (estimated mean change in total SvH score 1·8, 95% CI 0·9-2·6, SE 0·4) than did single-positive patients (0·5, 0·1-1·0, 0·2; estimated mean difference in the total change in SvH score 1·2, 95% CI 0·1-2·4, SE 0·5). There was no difference in radiographic progression between single positive patients and AMPA negative patients (estimated mean change in total SvH score 0·7, 95% CI 0·1-1·4, SE 0·3; estimated mean difference in the total change in SvH score -0·2, 95% CI -1·1 to 0·7, SE 0·4). This study suggests that the optimal prediction of future rates of radiographic progression in patients with rheumatoid arthritis will require an assessment of autoantibodies against multiple post-translationally modified proteins or peptides. The EU FP7 HEALTH programme, the Scottish Translational Medicine Research Collaboration, and the Chief Scientist Office Scotland.

Discovering Rheumatoid Arthritis During Pregnancy

Rheumatoid arthritis is an autoimmune mechanism disease that preferentially affects women. Remission from rheumatoid arthritis has often been associated with pregnancy.&#x0D; A 29-year-old woman presented with symmetrical inflammatory polyarthralgias of the large and small joints with morning stiffness estimated at 5 hours, and the Visual Analogue Scale at 80/100 associated with the joint swelling onset 12th week of amenorrhea. She has no medical history, third pregnancy, and no fetal loss has been reported. The physical examination of the day objectified five painful joints and two swollen joints. Disease activity was moderate. There was a biological inflammatory syndrome with a C-Reactive Protein (CRP) at 37.9 mg. Rheumatoid factor was positive at 214 IU (Standard &lt;14 IU), anti-citrullinated peptides antibodies at 99.6 IU (Standard &lt;17 IU).&#x0D; The pregnancy revealed rheumatoid arthritis positive to rheumatoid factor and citrullinated cyclic anti-peptide antibodies. &#x0D;

The significance of serum 14-3-3η level in rheumatoid arthritis patients.

RA is a systemic inflammatory condition characterized by chronic arthritis and often associated with irreversible joint damage. To assess the significance of serum level of 14-3-3η in RA and its association with clinical and serological features of the disease. This is a case-control study done on 80 participants. They were divided into 2 groups. Group 1: 40 rheumatoid arthritis patients compared to group 2: 40 healthy participants matched for age and sex. Laboratory investigations including complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPAs), and serum 14-3-3η were done to all participants. Radiological examination in the form of plain X-ray for hands and feet was done to all patients. Serum levels of 14-3-3η were significantly higher in RA patients compared to the control group (p < 0.001). Serum 14-3-3η was the only predictor of high Larsen's score (p = 0.013) on using linear regression analysis. Serum 14-3-3η can predict RA in healthy controls in univariate (p = 0.001) and multivariate (p = 0.004) analyses. The receiver operating characteristic (ROC) curve of 14-3-3η was constructed for discrimination between RA and control subjects. The best cut-off value was 61.9ng/mL, with fair AUC (0.773, p < 0.001), 95% CI (0.656-0.889), and the sensitivity and specificity of 14-3-3η for RA diagnosis as 65% and 95% respectively. Also, we constructed ROC curves for RF, ACPA, 14-3-3η, and their combinations; we found that the highest test sensitivity of 95.7% appeared on adding the 3 markers together, and the highest test specificity of 100% was detected on adding RF to ACPA, 14-3-3η to ACPA or the 3 molecules together. 14-3-3η could be a valuable marker for the diagnosis of RA patients and it may have prognostic value. Key Points • 14-3-3η is a valuable marker for the diagnosis of RA patients. • 14-3-3η reflects disease severity and joint damage in RA patients.

Efficacy and safety of rituximab in peripheral ulcerative keratitis associated with rheumatoid arthritis

ObjectivePeripheral ulcerative keratitis (PUK) is a rare but severe ocular complication of rheumatoid arthritis (RA). It can be considered as an ocular manifestation of rheumatoid vasculitis (RV). Our case series...

Cardiovascular Disease in Rheumatoid Arthritis: Risk Factors, Autoantibodies, and the Effect of Antirheumatic Therapies.

Objective:To scope the current published evidence on cardiovascular risk factors in rheumatoid arthritis (RA) focusing on the role of autoantibodies and the effect of antirheumatic agents.Methods:Two reviews were conducted in parallel: A targeted literature review (TLR) describing the risk factors associated with cardiovascular disease (CVD) in RA patients; and a systematic literature review (SLR) identifying and characterizing the association between autoantibody status and CVD risk in RA. A narrative synthesis of the evidence was carried out.Results:A total of 69 publications (49 in the TLR and 20 in the SLR) were included in the qualitative evidence synthesis. The most prevalent topic related to CVD risks in RA was inflammation as a shared mechanism behind both RA morbidity and atherosclerotic processes. Published evidence indicated that most of RA patients already had significant CV pathologies at the time of diagnosis, suggesting subclinical CVD may be developing before patients become symptomatic. Four types of autoantibodies (rheumatoid factor, anti-citrullinated peptide antibodies, anti-phospholipid autoantibodies, anti-lipoprotein autoantibodies) showed increased risk of specific cardiovascular events, such as higher risk of cardiovascular death in rheumatoid factor positive patients and higher risk of thrombosis in anti-phospholipid autoantibody positive patients.Conclusion:Autoantibodies appear to increase CVD risk; however, the magnitude of the increase and the types of CVD outcomes affected are still unclear. Prospective studies with larger populations are required to further understand and quantify the association, including the causal pathway, between specific risk factors and CVD outcomes in RA patients.