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ID PMID Title PublicationDate abstract
25574418 Gout initially mimicking rheumatoid arthritis and later cervical spine involvement. 2014 Gout is clinically characterized by episodes of monoarthritis, but if not treated properly, it can lead to a chronic polyarthritis, which may eventually mimic rheumatoid arthritis (RA). We present the case of a 59-year-old man, with a history of symmetrical polyarthritis of the large and small joints with later development of subcutaneous nodules, which was initially misdiagnosed as RA, being treated with prednisone and methotrexate for a long period of time. He complained of occipital pain and paresthesia in his left upper limb, and computed tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of an expansive formation in the cervical spine with compression of the medulla. He was admitted for spinal decompressive surgery and the biopsy specimen demonstrated a gouty tophus. Chronic gout can mimic RA and rarely involves the axial skeleton, and thus its correct diagnosis and the implementation of adequate therapy can halt the development of such damaging complications.
24106002 Albumin-based nanocomposite spheres for advanced drug delivery systems. 2014 Jan A novel drug delivery system incorporating human serum albumin, poly(lactic-co-glycolic acid, magnetite nanoparticles, and therapeutic agent(s) was developed for potential application in the treatment of diseases such as rheumatoid arthritis and skin cancer. An oil-in-oil emulsion/solvent evaporation (O/OSE) method was modified to produce a drug delivery system with a diameter of 0.5–2 μm. The diameter was mainly controlled by adjusting the viscosity of albumin in the discontinuous phase of the O/OSE method. The drug-release study showed that the release of drug and albumin was mostly dependent on the albumin content of the drug delivery system, which is very similar to the drug occlusion-mesopore model. Cytotoxicity tests indicated that increasing the albumin content in the drug delivery system increased cell viability, possibly due to the improved biocompatibility of the system. Overall, these studies show that the proposed system could be a viable option as a drug delivery system in the treatment of many illnesses, such as rheumatoid arthritis, and skin and breast cancers.
23959574 Rheumatoid arthritis pharmacotherapy and predictors of disease-modifying anti-rheumatic dr 2013 Aug 20 Disease-modifying anti-rheumatic drugs (DMARDs) are the cornerstone of rheumatoid arthritis (RA) pharmacotherapy and should be initiated promptly after RA diagnosis. We examined trends in use of traditional and biologic DMARDs, and non-DMARD treatments, among overall RA patients, and factors associated with DMARD initiation in the newly diagnosed RA. RA subjects identified with the Quebec administrative databases were followed between January 1, 2002, and December 31, 2008. DMARD use was characterized on November 1 of each year using cross-sectional analyses. For a subgroup of newly diagnosed subjects, we used multivariable logistic regressions to identify predictors of DMARD initiation within 12 months of diagnosis and survival analyses to appraise time to DMARD initiation. A total of 37,399 subjects were included (65.8 % ≥65 years; 70.5 % female). The percentage of subjects using any DMARDs increased over the study period from 41.4 % [95 % confidence interval (CI) 40.8-42.0] to 43.3 % (95 % CI 42.7-43.9). Among newly diagnosed RA, being followed by a rheumatologist was the strongest predictor of DMARD initiation (odds ratio 4.31; 95 % CI 3.73-4.97). Care by an internist, increasing calendar year, use of NSAIDs, corticosteroids, or opioids, and a history of hospitalization increased the likelihood of DMARD initiation. Older age, female, higher comorbidity score, number of medical visits pre-diagnosis, care by other specialists, and the use of acetaminophen were inversely associated with DMARD initiation. The probability of any DMARD initiation at 12 months was 38.5 %. Despite the clinical practice guideline recommendations for earlier aggressive RA management, DMARD use appears to be suboptimal in Quebec.
23352252 Nucleotide-binding oligomerization domain containing 2: structure, function, and diseases. 2013 Aug OBJECTIVES: To systematically review literature about the structure and function of nucleotide-binding oligomerization domain containing 2 (NOD2) and its disease association. METHODS: The English literature was searched using keywords "NOD2" and "disease". Relevant original and review articles were reviewed. RESULTS: NOD2 is an intracellular protein and shares similar molecular structure with NOD1, pyrin, and cryopyrin. There are more than 100 NOD2 gene mutations, some of which have been linked to diseases such as Crohn disease, Blau syndrome, and NOD2-associated autoinflammatory disease (NAID). The NOD2 variants located in the leucine-rich repeat (LRR) region are susceptible to Crohn disease, and the variants in the nucleotide-binding domain (NBD) and in between the NBD and LRR are associated with Blau syndrome and NAID, respectively. No disease association with the gene variants has been found in rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriasis/psoriatic arthritis, adult sarcoidosis, granulomatous polyangiitis, or multiple sclerosis. The potential association of the NOD2 variants with graft-versus-host-disease remains controversial. NOD2 functions mainly through RICK or RIP2 to activate p38 mitogen-activated protein kinases and NF-κB, resulting in inflammatory response, and enhanced autophagic activity. Biologic therapy may be beneficial for NOD2-associated diseases, and new drug development may be realized based upon the signaling pathways. CONCLUSIONS: NOD2 gene mutations are associated with several diseases, and some of the mutations are of diagnostic value in Blau disease and NAID. To understand the NOD2 function, disease association, and its pathogenesis is important given the ever increasing clinical significance of NOD2.
25364765 Cardio-miRNAs and onco-miRNAs: circulating miRNA-based diagnostics for non-cancerous and c 2014 Cardiovascular diseases and cancers are the leading causes of morbidity and mortality in the world. MicroRNAs (miRNAs) are short non-coding RNAs that primarily repress target mRNAs. Here, miR-24, miR-125b, miR-195, and miR-214 were selected as representative cardio-miRs that are upregulated in human heart failure. To bridge the gap between miRNA studies in cardiology and oncology, the targets and functions of these miRNAs in cardiovascular diseases and cancers will be reviewed. ACVR1B, BCL2, BIM, eNOS, FGFR3, JPH2, MEN1, MYC, p16, and ST7L are miR-24 targets that have been experimentally validated in human cells. ARID3B, BAK1, BCL2, BMPR1B, ERBB2, FGFR2, IL6R, MUC1, SITR7, Smoothened, STAT3, TET2, and TP53 are representative miR-125b targets. ACVR2A, BCL2, CCND1, E2F3, GLUT3, MYB, RAF1, VEGF, WEE1, and WNT7A are representative miR-195 targets. BCL2L2, ß-catenin, BIM, CADM1, EZH2, FGFR1, NRAS, PTEN, TP53, and TWIST1 are representative miR-214 targets. miR-125b is a good cardio-miR that protects cardiomyocytes; miR-195 is a bad cardio-miR that elicits cardiomyopathy and heart failure; miR-24 and miR-214 are bi-functional cardio-miRs. By contrast, miR-24, miR-125b, miR-195, and miR-214 function as oncogenic or tumor suppressor miRNAs in a cancer (sub)type-dependent manner. Circulating miR-24 is elevated in diabetes, breast cancer and lung cancer. Circulating miR-195 is elevated in acute myocardial infarction, breast cancer, prostate cancer and colorectal adenoma. Circulating miR-125b and miR-214 are elevated in some cancers. Cardio-miRs and onco-miRs bear some similarities in functions and circulation profiles. miRNAs regulate WNT, FGF, Hedgehog and other signaling cascades that are involved in orchestration of embryogenesis and homeostasis as well as pathogenesis of human diseases. Because circulating miRNA profiles are modulated by genetic and environmental factors and are dysregulated by genetic and epigenetic alterations in somatic cells, circulating miRNA association studies (CMASs) within several thousands of cases each for common non-cancerous diseases and major cancers are necessary for miRNA-based diagnostics.
24811458 Pharmacology of biosimilar candidate drugs in rheumatology: a literature review. 2014 Jan OBJECTIVE: To review current evidence concerning pharmacology of biosimilar candidates to be used in rheumatology. METHODS: A PubMed search up to August 2013 was performed using relevant search terms to include all studies assessing pharmacological properties of biosimilar candidates to be used in rheumatology. Data on study characteristics, type of intervention, pharmacokinetics (PK), pharmacodynamics (PD) and bioequivalence ratios was extracted. RESULTS: Of 280 articles screened, 5 fulfilled our inclusion criteria. Two trials, PLANETAS and PLANETRA, compared CT-P13 and infliximab in patients with active ankylosing spondylitis and rheumatoid arthritis, respectively. PK bioequivalence was demonstrated in the phase 1 PLANETAS trial by highly comparable area under the curve (AUC) and maximum drug concentrations (Cmax), whose geometric mean ratios fell between the accepted bioequivalence range of 80-125%. Equivalence in efficacy and safety was demonstrated in the phase 3 PLANETRA trial. Two phase 1 trials comparing etanercept biosimilar candidates TuNEX and HD203 in healthy volunteers showed a high degree of similarity in AUC and Cmax, with respective geometric mean ratios between PK bioequivalence range. The last included trial referred to GP2013, a rituximab biosimilar candidate, which demonstrated PK and PD bioequivalence to reference product in three different dosing regimens in cynomolgus monkeys. CONCLUSION: Infliximab, etanercept and rituximab biosimilar candidates have demonstrated PK bioequivalence in the trials included in this review. CT-P13 has recently been approved for use in the European market and the remaining biosimilar candidates are currently being tested in patients with rheumatoid arthritis.
25349698 Ipilimumab in patients with melanoma and autoimmune disease. 2014 Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), an immune-checkpoint receptor and regulator of T-cell activation, has become an important therapeutic target for immunotherapy in cancer and autoimmune diseases. To date, clinical trials involving cancer immunotherapies, such checkpoint blocking antibodies directed at CTLA-4 (ipilimumab), have excluded patients with underlying autoimmune disease given concern for potential triggering of autoimmune exacerbations. We present the first known cases to our knowledge of two patients with active autoimmune diseases who received ipilimumab. In this limited clinical experience, no serious exacerbations of underlying autoimmunity have yet been observed, and one patient benefited from ipilimumab. These cases advocate for further investigation of the safety of cancer immunotherapies in cancer patients with underlying autoimmune conditions in carefully designed clinical trials with cautious monitoring.
23615838 Silica exposure is associated with an increased risk of developing ACPA-positive rheumatoi 2013 Apr 25 OBJECTIVES: Silica exposure has been associated with an increased risk of developing rheumatoid arthritis (RA), especially among smokers. In this study, we aimed at examining the association between silica exposure (and its interaction with smoking) and the risk of RA in the Malaysian population. METHODS: In total, 149 cases and 213 matched controls, all men, were included between August 2005 and December 2009. A case was defined as a person with early diagnosed RA using the 1987 American College of Rheumatology criteria for RA. Controls were randomly selected matched on sex, age and residential area. Silica exposure was defined as exposure to stone dust, rock drilling or stone crushing, and smoking status was categorized as ever/never cigarette smoking. RESULTS: An increased risk of anti-citrullinated protein antibody (ACPA)-positive RA (OR = 2.4, 95 % CI 1.0-5.6) was observed among those exposed to silica. Ever-smokers exposed to silica had a particularly high risk of developing ACPA-positive RA (OR = 7.5, 95 % CI 2.3-24.2), compared with never-smokers not exposed to silica. No association was found regarding ACPA-negative RA. CONCLUSION: Our data demonstrate that exposure to both silica and cigarette smoke comprise risks for developing RA in the Malaysian genetic context. The findings expand a link between environmental lung exposures and ACPA-positive RA to Asian populations.
25378951 Systemic AA amyloidosis: epidemiology, diagnosis, and management. 2014 The term "amyloidosis" encompasses the heterogeneous group of diseases caused by the extracellular deposition of autologous fibrillar proteins. The global incidence of amyloidosis is estimated at five to nine cases per million patient-years. While amyloid light-chain (AL) amyloidosis is more frequent in developed countries, amyloid A (AA) amyloidosis is more common in some European regions and in developing countries. The spectrum of AA amyloidosis has changed in recent decades owing to: an increase in the median age at diagnosis; a percent increase in the frequency of primary AL amyloidosis with respect to the AA type; and a substantial change in the epidemiology of the underlying diseases. Diagnosis of amyloidosis is based on clinical organ involvement and histological evidence of amyloid deposits. Among the many tinctorial characteristics of amyloid deposits, avidity for Congo red and metachromatic birefringence under unidirectional polarized light remain the gold standard. Once the initial diagnosis has been made, the amyloid subtype must be identified and systemic organ involvement evaluated. In this sense, the (123)I-labeled serum amyloid P component scintigraphy is a safe and noninvasive technique that has revolutionized the diagnosis and monitoring of treatment in systemic amyloidosis. It can successfully identify anatomical patterns of amyloid deposition throughout the body and enables not only an initial estimation of prognosis, but also the monitoring of the course of the disease and the response to treatment. Given the etiologic diversity of AA amyloidosis, common therapeutic strategies are scarce. All treatment options should be based upon a greater control of the underlying disease, adequate organ support, and treatment of symptoms. Nevertheless, novel therapeutic strategies targeting the formation of amyloid fibrils and amyloid deposition may generate new expectations for patients with AA amyloidosis.
25158802 Impact of rheumatic diseases on oral health and quality of life. 2015 Apr OBJECTIVE: We investigated the effects of rheumatic diseases on oral symptoms, health habits, and quality of life in subjects with and without rheumatic diseases. The hypothesis was that patients with rheumatic diseases have more oral symptoms impairing their quality of life than healthy controls. METHODS: A questionnaire was mailed to a random sample of 1500 members of the Finnish Rheumatism Association, including those with and without rheumatic diseases. We focused on symptoms of the mouth and temporomandibular area, and health habits. Oral Health Impact Profile (OHIP14) was used to evaluate the oral health-related quality of life. We analyzed differences between subjects with and without rheumatic diseases, controlled for age, gender, smoking, and non-rheumatic chronic diseases. RESULTS: Completed questionnaires were received from 995 participants (response rate 66%). Of them, 564 reported rheumatic disease, 431 were used as controls. The patients reported significantly more all orofacial symptoms than controls. Severe dry mouth was reported by 19.6% of patients and 2.9% of controls (P < 0.001), and temporomandibular joint symptoms by 59.2% and 27.2% (P < 0.001), respectively. In the OHIP-14 questionnaire, the mean total score was significantly higher in patients (8.80 ± 11.15) than in controls (3.93 ± 6.60; P < 0.001). CONCLUSION: The study hypothesis was confirmed by showing that the patients with rheumatic diseases reported oral discomfort and reduced quality of life more often when compared with controls.
24796836 Biomechanical comparison of first metatarsophalangeal joint arthrodeses using triple-threa 2014 Jun BACKGROUND: Triple-threaded, cannulated headless screws of varying thread diameters and pitch are designed to maintain thread length across the arthrodesis plane, provide joint compression, and reduce countersinking. This study tested the biomechanical fixation strength of conventional partially threaded lag screws compared to triple-threaded headless screws in first metatarsophalangeal joint arthrodesis. METHODS: First metatarsophalangeal joint arthrodesis using a crossed screw technique was performed on 11 paired, preserved cadaver first rays with two 4.0-mm triple-threaded, cannulated headless screws or two 4.0-mm partially threaded, cannulated lag screws. The constructs were tested to failure through dorsally directed cantilever bending. RESULTS: The triple-threaded, cannulated headless screws displayed significantly greater bending stiffness (p=0.017) and failure load (p=0.040) during load-to-failure testing compared to the partially threaded, cannulated lag screws. CONCLUSIONS: Triple-threaded, cannulated headless screws may be a viable alternative to partially threaded lag screws in first metatarsophalangeal arthrodesis.
24693288 Contact frequency, travel time, and travel costs for patients with rheumatoid arthritis. 2014 Objectives. To investigate travel time, and travel cost related to contacts with health care providers for patients with rheumatoid arthritis (RA) during a three-month period. Methods. Patient-reported travel time and travel cost were obtained from 2847 patients with RA. Eleven outpatient clinics across Denmark recruited patients to the study. Data collected included frequency, travel time and travel costs for contacts at rheumatology outpatient clinics, other outpatient clinics, general practitioners, privately practicing medical specialists, inpatient hospitals and accident and emergency departments. Results. Over a 3-month period, patients with RA had on average 4.4 (sd 5.7) contacts with health care providers, of which 2.8 (sd 4.0) contacts were with rheumatology outpatient clinics. Private car and public travel were the most frequent modes of travel. The average patient spent 63 minutes and 13 € on travelling per contact, corresponding to a total of 4.6 hours and 56 € during the 3-month period. There was great variation in patient travel time and costs, but no statistically significant associations were found with clinical and sociodemographic characteristics. Conclusion. The results show that patients with RA spend private time and costs on travelling when they seek treatment. These findings are particularly important when analyzing social costs associated with RA.
24636988 [Scleritis and episcleritis: diagnosis and treatment]. 2014 Sep Episcleritis and scleritis are distinct entities with regard to visual prognosis, risk of associated systemic disease, and treatment. The pertinence of the clinical classification of episcleritis and scleritis established in 1976 still persists, with significant differences in terms of visual prognosis, associated general conditions, and therapeutic choices according to each scleritis subtype. Episcleritis requires rarely to be referred to a tertiary care centre, and if so it has to be monitored similarly to scleritis. In this paper, an analysis of 1358 scleritis cases from the main distinct large series published since 1976 shows a mean proportion of 8% of infectious aetiologies (mainly herpes viruses), and 28% of systemic diseases with two main subgroups: inflammatory rheumatisms 12.8%, and systemic vasculitis 7.8%. Overall, the risk for visual loss following scleritis is around 16%. However, the risks of associated systemic disease and visual loss are both highly variable according to the type of scleritis, and culminate at 80% and 50% in the necrotizing subtype respectively. As compared with older series, the proportion of necrotizing scleritis is lower in recent series which is likely due to the advances obtained over the past 20 years in immunomodulatory therapy, as well as its wide use in the treatment of the main systemic conditions associated with scleritis. The treatment of scleritis should be managed by physicians who are experts in the use of immunosuppressive drugs that may be required in one out of two affected patients.
24222845 DNA damage in rheumatoid arthritis: an age-dependent increase in the lipid peroxidation-de 2013 Objective. To evaluate what types of DNA damages are detected in rheumatoid arthritis (RA). Methods. The DNA adducts such as 8-oxo-hydroxy-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), 1,N(6)-etheno-2'-deoxyadenosine ( ε dA), and heptanone-etheno-2'-deoxycytidine (H ε dC) in genomic DNAs, derived from whole blood cells from 46 RA patients and 31 healthy controls, were analyzed by high-performance liquid chromatography tandem mass spectrometry, and their levels in RA patients and controls were compared. In addition, correlation between DNA adducts and clinical parameters of RA was analyzed. Results. Compared with controls, the levels of H ε dC in RA were significantly higher (P < 0.0001) and age dependent (r = 0.43, P < 0.01), while there was no significant difference in 8-oxo-dG and ε dA accumulation between RA patients and controls. H ε dC levels correlated well with the number of swollen joints (r = 0.57, P < 0.0001) and weakly with the number of tender joints (r = 0.26, P = 0.08) of RA patients, while they did not show a significant association with serological markers such as C-reactive protein and matrix metalloproteinase 3. Conclusion. These findings indicate that H ε dC may have some influence on the development of RA and/or its complications.
24022393 Long-term sustained remission in a cohort study of patients with rheumatoid arthritis: cho 2013 Sep 10 OBJECTIVES: Remission is a widely accepted goal for treatment of rheumatoid arthritis (RA) but has to be sustained to arrest joint damage and disability. However, appropriate criteria for the assessment of sustained remission in long-term studies are not established. Therefore, we have compared the disease activity score calculated on 28 joints (DAS28) remission criterion, the Simplified Disease Activity Index less than 3.3 remission criterion (SDAI Cr) and the new Boolean-based set of criteria (Boolean Cr), and assessed the association of these criteria with radiographic and functional outcome. DESIGN: Prospective, long-term observational study of patients with early RA. SETTING: Secondary level of care; six participating centres from southern Sweden; both urban and rural populations. PARTICIPANTS: 698 patients were consecutively included in the study and 527 remained at the 8-year follow-up visit. Almost all patients were Caucasians, of which 64% were women. To be included, a patient, 18 years or older, had to fulfil the 1987 American College of Rheumatology criteria for RA and have a disease duration of no more than 1 year. RESULTS: Sustained remission was most common by the DAS28 Cr (14%), while 3% met the Boolean Cr and 5% the SDAI Cr, the latter figures increasing to 9% and 8%, respectively, when the patient's global assessment was excluded. Radiographic joint damage was common but least pronounced in patients in sustained remission by all criteria. Sustained remission was associated with rapid and lasting improvement in function assessed by the Health Assessment questionnaire, irrespective of criteria. CONCLUSIONS: The DAS28 Cr acquired more patients in sustained remission compared with the other criteria. In spite of that, radiographic damage and disability were not worse than that seen by other criteria and the patients' perspective was preserved. The DAS28 Cr may therefore still be used in long-term observational studies until more accurate criteria are available.
25191473 Chest high resolution computed tomography findings in connective tissue diseases. 2013 BACKGROUND: Lung disorders are important for prognosis of connective tissue disease (CTD). Thus, chest radiography, High Resolution Computed Tomography (HRCT) of the chest and ultrasonic echocardiogram are suggested after the diagnosis of these conditions. The purpose of this study was to evaluate chest HRCT findings in patients with CTD. MATERIALS AND METHODS: In this descriptive cross-sectional study, we evaluated HRCT findings in patients with (CTD) hospitalized in Imam Reza Hospital in Mashhad from 2006 - 2011. Patients' age, sex, type of rheumatic disease and HRCT results were collected and analyzed by SPSS version 16.0 software. RESULTS: Out of 75 patients (78.67% females, 21.33% males with a mean age of 41.6 years), 56% had respiratory symptoms. Scleroderma was the most common disease (38.6%) followed by rheumatoid arthritis (26.6%) and systemic lupus erythematosus (14.6%). Interstitial tissue involvement of the lung was the most frequent finding in patients with scleroderma, dermatomyositis, polymyositis and Sjogren's syndrome (48.3%, 57.1%, 60% and 66.7%, respectively). Pleural thickening was the most common finding in patients with rheumatoid arthritis (45%). Pleural effusion was the most frequent finding in patients with systemic lupus erythematosus (45.4%). Lymphadenopathy and bronchiectasis had the lowest prevalence (1.3%). CONCLUSION: Our data shows that interstitial tissue involvement, pleural thickening and pleural effusion are common in patients with rheumatic diseases which is consistent with some previous studies.
24937321 Nonclinical safety of mavrilimumab, an anti-GMCSF receptor alpha monoclonal antibody, in c 2014 Sep 1 Mavrilimumab (CAM-3001) is an investigational human IgG4 monoclonal antibody (MAb) targeting GM-CSF receptor alpha which is currently being developed for the treatment of RA. GM-CSF plays a central role in the pathogenesis of rheumatoid arthritis (RA) through the activation, differentiation, and survival of macrophages and neutrophils. To support clinical development, the nonclinical safety of mavrilimumab was evaluated in several studies with cynomolgus monkeys as the pharmacologically relevant species. Comprehensive toxicity parameters were assessed in each study, and treatment duration ranged from 4 to 26weeks. Mavrilimumab has an acceptable safety profile in monkeys with no changes in any parameters other than microscopic findings in lung. In several studies, minimal accumulation of foamy alveolar macrophages was observed. This finding was only seen in studies of at least 11weeks duration, was reversible following a dose-free recovery period and was considered non-adverse. At higher dose levels (≥30mg/kg/week), in a 26-week repeat-IV dose study, the presence of lung foreign material, cholesterol clefts, and granulomatous inflammation was also observed in a few animals and was considered adverse. The dose- and time-related accumulation of foamy macrophages in lung following exposure to mavrilimumab observed in several NHP studies was expected based upon the known role of GM-CSFRα signaling in the function of alveolar macrophages. Overall, a clean no-observed-adverse-effect-level (NOAEL) without any effects in lung was established and provided adequate clinical safety margins. In clinical studies in RA patients, mavrilimumab has demonstrated good clinical activity with adequate safety to support further clinical development. A Phase 2b study of mavrilimumab in subjects with RA is in progress.
25120260 Biosensor analysis of anti-citrullinated protein/peptide antibody affinity. 2014 Nov 15 Anti-citrullinated protein/peptide antibodies (ACPAs) are detected in rheumatoid arthritis (RA) sera and because of their strict association with the disease are considered marker antibodies, probably endowed with pathogenic potential. Antibody affinity is one of the parameters affecting pathogenicity. Three diagnostic citrullinated peptides-viral citrullinated peptide 1 (VCP1) and VCP2 derived from Epstein-Barr virus (EBV)-encoded proteins and histone citrullinated peptide 1 (HCP1) derived from histone H4-were synthesized as tetrameric multiple antigen peptides and immobilized on sensor chips CM5 type in a Biacore T100 instrument. Specific binding of purified antibodies from RA patients to the three peptides was analyzed by surface plasmon resonance using two arginine-containing sequences as controls. Employing a 1:1 binding model for affinity constant calculation, ACPAs interacted with VCP1 and VCP2 with lower apparent affinity (10(-6) M>KD>10(-7) M) and interacted with HCP1 with higher apparent affinity (KD=10(-8) M). The results indicate that the binding to citrullinated peptides is characterized by wide differences in affinity, with slower association and faster dissociation rates in the case of antibodies to viral citrullinated peptides as compared with antibodies specific for the histone peptide. This biosensor analysis shows the high cross-reactivity of purified ACPAs that bind other citrullinated peptides besides the one used for purification.
24176675 Carbamylation and antibodies against carbamylated proteins in autoimmunity and other patho 2014 Mar Carbamylation is a non-enzymatic post-translational modification in which cyanate binds to molecules containing primary amine or thiol groups and forms carbamyl groups. Cyanate is in equilibrium with urea in body fluid and increased carbamylation was first reported in patients with increased urea levels such as patients suffering renal diseases. Next, increased carbamylation related to inflammation has also been described in other conditions such as cardiovascular disease. Recently, a new consequence of carbamylation has been observed: induction of an autoantibody response. We identified anti-carbamylated protein (anti-CarP) antibodies in rheumatoid arthritis (RA) patients and in patients having 'pre-RA' symptoms, arthralgia. The presence of anti-CarP antibodies in arthralgia patients is associated with an increased risk of developing RA. The presence of anti-CarP antibodies in RA patients is associated with more severe joint damage in RA patients who do not have anti-citrullinated protein antibodies. It is currently unknown to what extent carbamylation and/or the formation of anti-CarP antibodies contributes to the disease processes of chronic diseases such as renal diseases, cardiovascular diseases and RA. This review summarizes the current knowledge on carbamylation and the formation of anti-CarP antibodies and discusses their possibly important implications.
24138820 Experience with the Coonrad-Morrey total elbow arthroplasty: 78 consecutive total elbow ar 2013 Nov BACKGROUND: The Coonrad-Morrey total elbow arthroplasty is a linked implant. This study investigated the hypotheses that reliable results can be obtained in rheumatoid patients and in traumatic conditions and that the survival rate is similar to or better than what has been published for nonlinked implants. METHODS: Surgery was performed on 70 consecutive patients (78 elbows) for an inflammatory arthritis (45 elbows) or a traumatic condition (33 elbows: 18 acute fractures of the distal humerus, 10 nonunions, and 5 post-traumatic arthritis). RESULTS: At an average of 5 years of follow-up (2 to 11 years), the mean Mayo Elbow Performance Score for the group that had inflammatory arthritis (89 ± 13 points) was significantly higher than that for the group with a traumatic condition (80 ± 17 points). The QuickDASH score was not significantly different according to the etiology. Radiolucencies were observed in 17 cases around the humeral component and in 14 cases around the ulnar component. Bushing wear was observed in 14 cases. There were 27 complications, and 9 of them went to a revision procedure. The survival rate was 97.7% at 5 years and 91.0% at 10 years if we consider revision for aseptic loosening as an endpoint. CONCLUSIONS: The Coonrad-Morrey total elbow arthroplasty allows treatment of a large spectrum of causes with satisfactory results. Better results have been obtained for rheumatoid patients than for patients with trauma. The rate of complication remains high even if the rate of implant revision stays low. However, the increased incidence of lucent lines around the ulnar component with follow-up and bushing wear are of concern.