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ID PMID Title PublicationDate abstract
23133751 Pathological role of interleukin-6 in psoriatic arthritis. 2012 Psoriatic arthritis (PsA) is a clinical manifestation of psoriatic disease. Although the pathogenesis of PsA remains unknown, PsA can be managed by treatments similar to those used for rheumatoid arthritis (RA). Because interleukin-(IL-) 6 has been suggested to have a pathogenic role in PsA, a humanized anti-IL-6 receptor antibody tocilizumab treatment for PsA was recently tried. However, the efficacy of tocilizumab for PsA was not favorable. This suggests that the pathogenic roles of IL-6 in PsA and RA are different. In RA, tumor necrosis factor (TNF) primarily contributes to the arthritis effector phase and IL-6 contributes to the arthritis priming phase. In PsA, the TNF-related effector phase is similar to that in RA, but the IL-6-related priming phase might not be critical. This paper discusses the role of IL-6 in PsA.
31643570 Penicillamine. 2012 Penicillamine is chelating agent used to decrease copper stores in Wilson disease, which also has immunomodulatory activity in rheumatic diseases such as rheumatoid arthritis, scleroderma and systemic lupus erythematosus. Penicillamine is capable of causing hypersensitivity reactions, some of which are accompanied by liver injury which is typically cholestatic.
22690382 Epidemiology of psoriatic arthritis. 2012 Jun 5 Epidemiological studies on psoriatic arthritis have long been hampered by the absence of widely accepted classification criteria. The development of the CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria has recently provided the framework for conducting epidemiological studies in psoriatic arthritis using uniform recruitment criteria. However, so far, only a minority of studies have adopted such criteria. In addition to the lack of shared classification criteria, differences in study settings, designs, and ascertainment methods have contributed to yield substantial disparities in the estimates of the incidence (from 3,02 to 23,1 cases per 100,000 people) and prevalence (from 49,1 to 420 cases per 100,000 people) of psoriatic arthritis around the globe. Overall, the available data suggests that the prevalence of psoriasis in the general population is approximately 2-3%, with about a third of patients with psoriasis having arthritis. Therefore, psoriatic arthritis may affect 0,3- 1,0% of the population, a frequency not dissimilar from that of rheumatoid arthritis. Future epidemiological studies should be carried out in larger numbers of patients diagnosed using consistent criteria.
23997746 A three-dimensional finite element analysis of finger joint stresses in the MCP joint whil 2012 Sep The goal of this study was to develop a three-dimensional finite element model of the metacarpophalangeal (MCP) joint to characterize joint contact stresses incurred during common daily activities. The metacarpal and proximal phalanx were modeled using a COMSOL-based finite element analysis. Muscle forces determined from a static force analysis of two common activities (pen grip and carrying a weight) were applied to the simulation to characterize the surface stress distributions at the MCP joint. The finite element analysis predicted that stresses as high as 1.9 MPa, similar in magnitude to stresses experienced at the hip, may be experienced by the subchondral bone in the MCP joint. The internal structure and material properties of the phalanges were found to play a significant role in both the magnitude and distribution of stresses, but the dependence on cancellous bone modulus was not as severe as predicted by previous two dimensional models.
22229089 Interstitial lung disease in rheumatoid arthritis in the era of biologics. 2011 Interstitial lung disease (ILD) represents a severe manifestation in connective tissue diseases (CTD), with an overall incidence of 15%, and it is still a challenge for clinicians evaluation and management. ILD is the most common manifestation of lung involvement in Rheumatoid Arthritis (RA), observed in up to 80% of biopsies, 50% of chest Computed Tomography (CT) and only 5% of chest radiographs. Histopatological patterns of ILD in RA may present with different patterns, such as: usual interstitial pneumonia, non specific interstitial pneumonia, desquamative interstitial pneumonia, organizing pneumonia, and eosinophilic infiltration. The incidence of ILD in RA patients is not only related to the disease itself, many drugs may be in fact associated with the development of pulmonary damage. Some reports suggest a causative role for TNFα inhibitors in RA-ILD development/worsening, anyway, no definitive statement can be drawn thus data are incomplete and affected by several variables. A tight control (pulmonary function tests and/or HRCT) is mandatory in patients with preexisting ILD, but it should be also performed in those presenting risk factors for ILD and mild respiratory symptoms. Biologic therapy should be interrupted, and, after excluding triggering infections, corticosteroids should be administered.
22196999 Chronic eosinophilic pneumonia: autoimmune phenomenon or immunoallergic disease? Case repo 2012 May Eosinophilic pneumonia is classified by its acute or chronic presentation, the distinguishing characteristics of which are based on the presence of cough, dyspnea, fever and pulmonary infiltrates with accumulation of inflammatory cells, predominantly eosinophils. The association of eosinophilia and rheumatologic disorders is well known, as in the case of eosinophilic fasciitis and the Churg-Strauss syndrome. The coexistence of chronic eosinophilic pneumonia and rheumatoid arthritis has been reported, either early rheumatoid arthritis of definitive disease. The pathophysiological role of eosinophils in autoimmune diseases is not well defined, however it has been shown that the production of pro-inflammatory cytokines stimulate and activates different cell groups, and can simultaneously induce autoantibodies and/or increased infiltration of eosinophils in various tissues, without an underlying autoimmune disease. The case of a young woman with rheumatic chronic eosinophilic pneumonia manifestations and the presence of autoantibodies, which resolved spontaneously, is presented here.
21876832 Myeloid-related protein activity in rheumatoid arthritis. 2011 SA100A8, SA100A9, and SA100A12 are members of the myeloid-related protein class. SA100A8 and SA100A9, also known as MRP-8 and MRP-14, respectively, are intracellular Ca(2+)-binding proteins produced mainly by neutrophils and monocytes where they exist as a heterodimeric complex in the cytosol. The MRP-8/-14 complex has been shown to promote chronic inflammation associated with rheumatoid arthritis (RA). In that regard, MRP-8 and MRP-14 regulate the inflammatory response through their capacity to recruit neutrophils and monocytes to target tissues resulting in attachment to endothelium. MRPs also activate the signal transduction pathway principally involving the stress-activated/mitogen-activated protein kinases. MRP-8/MRP-14 also increased nitric oxide synthesis. Most recently, the MRP-8/MRP-14 complex was shown to be a novel ligand for the toll-like receptors (TLRs) and TLR-4, in particular. Engagement of TLRs by the MRP-8/-14 complex may be particularly important for activating antigen-presenting dendritic cells which regulate critical autoimmune responses that promote chronic synovitis characteristic of RA.
21367665 Immune mechanisms of new therapeutic strategies in MS: teriflunomide. 2012 Jan At present, a series of oral disease-modifying agents is being introduced for the treatment of multiple sclerosis. With the exception of laquinimod, the "new" oral compounds have already been approved for other indications such as organ transplantation (FTY720), psoriasis (dimethylfumarate), hairy cell leukemia (cladribine), and rheumatoid arthritis (leflunomide). Leflunomide is the prodrug of teriflunomide which is the latest compound that has successfully been tested in a large phase III clinical trial in relapsing MS. Due to its favorable safety profile and its efficacy in rheumatoid arthritis where the aberrant immune response is in various aspects similar to the autoimmune reaction in MS patients, teriflunomide is a promising treatment option for MS patients. Here, we review the most important cell biological and immunological modes of action of teriflunomide, report on the available data on its pharmacokinetics in humans, and summarize the recent clinical trials of teriflunomide in relapsing MS.
21733351 Life with arthritis in Canada: a personal and public health challenge. 2011 Jun "Arthritis" describes more than 100 conditions that affect the joints, the tissues that surround joints and other connective tissue. These conditions range from relatively mild forms of tendonitis and bursitis to systemic illnesses, such as rheumatoid arthritis. Life with arthritis in Canada: a personal and public health challenge presents the latest knowledge about arthritis in the Canadian population and its wide-ranging impact. It provides an overview of the impact of arthritis, and is designed to increase public awareness of the importance of prevention and timely management. Although progress has been made on interventions, arthritis remains common, disabling and costly. Increasing participation in physical activity and maintaining a healthy body weight may help to mitigate the effects of arthritis.
21912431 Management of psoriatic arthritis from the view of the dermatologist. 2011 Sep 13 Psoriatic arthritis (PsA) is an inflammatory seronegative spondyloarthropathy associated with psoriasis. Although the main assessment measures for PsA are borrowed from the standard criteria used to assess rheumatoid arthritis, a number of new criteria such as the PsAJAI and CPDAI are being developed specifically for PsA. Long-term consequences of untreated PsA include persistent inflammation, progressive joint damage and, in many cases, substantial functional limitations, pain and disability. Moreover, patients with PsA have an increased mortality risk and an increased risk of developing cardiovascular disease and metabolic syndrome. Both GRAPPA and the AAD have developed treatment guidelines, which are discussed here. Psoriasis commonly precedes arthritic symptoms; thus, dermatologists are ideally placed to make the initial diagnosis of PsA and treat it appropriately, affording the opportunity to slow disease progression, improve physical function and enhance quality of life. This Review explores the management of patients with PsA, with a particular emphasis on assessment tools, long-term consequences and treatment issues from the viewpoint of the dermatologist.
22363878 Growth hormone deficiency, short stature, and juvenile rheumatoid arthritis in a patient w 2011 Autoimmune polyglandular syndromes (APSs) include a cluster of autoimmune and nonautoimmune conditions which have been classified into subtypes. APSs type 1 is characterized by at least two of the following: chronic mucocutaneous candidiasis, chronic hypoparathyroidism, and autoimmune Addison's disease (AD). We report the chronological history of a female patient who presented with features most consistent with APS type 1, along with growth hormone deficiency and juvenile rheumatoid arthritis (JRA). In terms of her autoimmune diagnoses, she first presented with JRA at three years of age, then hypocalcemia and hypoparathyroidism at five years of age, type 1 diabetes (DM 1) at age eleven years, adrenal insufficiency at age fourteen years, recurrent mucocutaneous candidiasis as a teenager, growth hormone deficiency at age fourteen years leading to significant short stature, primary amenorrhoea, and hypogonadism, and finally alopecia at age twenty-six years. In addition to this, she has suffered other nonautoimmune medical problems including a Tetralogy of Fallot with a surgical repair at age six years. On review of the medical literature, we found no other previously reported case with this unique combination of medical problems.
23028406 The p38 MAPK Pathway in Rheumatoid Arthritis: A Sideways Look. 2012 The p38 mitogen-activated protein kinase (MAPK) signaling pathway has been strongly implicated in many of the processes that underlie the pathology of rheumatoid arthritis (RA). For many years it has been considered a promising target for development of new anti-inflammatory drugs with which to treat RA and other chronic immune-mediated inflammatory diseases. However, several recent clinical trials have concluded in a disappointing manner. Why is this so, if p38 MAPK clearly contributes to the excessive production of inflammatory mediators, the destruction of bone and cartilage? We argue that, to explain the apparent failure of p38 inhibitors in the rheumatology clinic, we need to understand better the complexities of the p38 pathway and its many levels of communication with other cellular signaling pathways. In this review we look at the p38 MAPK pathway from a slightly different perspective, emphasising its role in post-transcriptional rather than transcriptional control of gene expression, and its contribution to the off-phase rather than the on-phase of the inflammatory response.
22313603 Autologous stromal vascular fraction therapy for rheumatoid arthritis: rationale and clini 2012 Feb 8 Advancements in rheumatoid arthritis (RA) treatment protocols and introduction of targeted biological therapies have markedly improved patient outcomes, despite this, up to 50% of patients still fail to achieve a significant clinical response. In veterinary medicine, stem cell therapy in the form of autologous stromal vascular fraction (SVF) is an accepted therapeutic modality for degenerative conditions with 80% improvement and no serious treatment associated adverse events reported. Clinical translation of SVF therapy relies on confirmation of veterinary findings in targeted patient populations. Here we describe the rationale and preclinical data supporting the use of autologous SVF in treatment of RA, as well as provide 1, 3, 6, and 13 month safety outcomes in 13 RA patients treated with this approach.
22429183 B cells as effectors and regulators of sex-biased arthritis. 2012 Aug B cells have been implicated both with pathogenic as well as protective capabilities in induction and regulation of autoimmune diseases. Rheumatoid arthritis (RA) is an autoimmune disease that occurs more often in women than men. A significant role of B cells as antibody producing and antigen-presenting cells has been demonstrated in RA. Predisposition to RA is associated with the presence of certain HLA class II alleles that share sequences with DRB1*0401. To determine the role of HLA genes and B cells in vivo, we have generated transgenic mice carrying HLA genes, DRB1*0401 and DQ8, known to be associated with susceptibility to RA. Humanized mice can be induced to develop arthritis that mimics human disease in clinical, histopathological and sex bias. Effect of hormones on immune cells and their function has been described in humans and mice and has been suggested to be the major reason for female bias of autoimmune diseases. An immune response to an antigen requires presentation by HLA molecules thus suggesting a critical role of MHC in combination with sex hormones in susceptibility to develop rheumatoid arthritis. Based on our observations, we hypothesize that modulation of B cells by estrogen, presentation of modified antigens by DR4 and production of antigen-specific B cell modulating cytokines leads to autoreactivity in females. These data suggest that considering patient's sex may be crucial in selecting the optimal treatment strategy. Humanized mice expressing RA susceptible and resistant haplotype provide a means to investigate mechanism sex-bias of arthritis and future strategies for therapy.
22541596 Annotation Analysis for Testing Drug Safety Signals using Unstructured Clinical Notes. 2012 Apr 24 BACKGROUND: The electronic surveillance for adverse drug events is largely based upon the analysis of coded data from reporting systems. Yet, the vast majority of electronic health data lies embedded within the free text of clinical notes and is not gathered into centralized repositories. With the increasing access to large volumes of electronic medical data-in particular the clinical notes-it may be possible to computationally encode and to test drug safety signals in an active manner. RESULTS: We describe the application of simple annotation tools on clinical text and the mining of the resulting annotations to compute the risk of getting a myocardial infarction for patients with rheumatoid arthritis that take Vioxx. Our analysis clearly reveals elevated risks for myocardial infarction in rheumatoid arthritis patients taking Vioxx (odds ratio 2.06) before 2005. CONCLUSIONS: Our results show that it is possible to apply annotation analysis methods for testing hypotheses about drug safety using electronic medical records.
21304067 Fenofibrate, a PPAR{alpha} agonist, decreases atrogenes and myostatin expression and impro 2011 May Arthritis is a chronic inflammatory illness that induces cachexia, which has a direct impact on morbidity and mortality. Fenofibrate, a selective PPARα activator prescribed to treat human dyslipidemia, has been reported to decrease inflammation in rheumatoid arthritis patients. The aim of this study was to elucidate whether fenofibrate is able to ameliorate skeletal muscle wasting in adjuvant-induced arthritis, an experimental model of rheumatoid arthritis. On day 4 after adjuvant injection, control and arthritic rats were treated with 300 mg/kg fenofibrate until day 15, when all rats were euthanized. Fenofibrate decreased external signs of arthritis and liver TNFα and blocked arthritis-induced decreased in PPARα expression in the gastrocnemius muscle. Arthritis decreased gastrocnemius weight, which results from a decrease in cross-section area and myofiber size, whereas fenofibrate administration to arthritic rats attenuated the decrease in both gastrocnemius weight and fast myofiber size. Fenofibrate treatment prevented arthritis-induced increase in atrogin-1 and MuRF1 expression in the gastrocnemius. Neither arthritis nor fenofibrate administration modify Akt-FoxO3 signaling. Myostatin expression was not modified by arthritis, but fenofibrate decreased myostatin expression in the gastrocnemius of arthritic rats. Arthritis increased muscle expression of MyoD, PCNA, and myogenin in the rats treated with vehicle but not in those treated with fenofibrate. The results indicate that, in experimental arthritis, fenofibrate decreases skeletal muscle atrophy through inhibition of the ubiquitin-proteasome system and myostatin.
22311593 Detection of multiple autoantibodies in patients with ankylosing spondylitis using nucleic 2012 Feb Ankylosing spondylitis (AS) is a common, inflammatory rheumatic disease that primarily affects the axial skeleton and is associated with sacroiliitis, uveitis, and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine whether plasma from patients with AS contained autoantibodies and, if so, characterize and quantify this response in comparison to patients with rheumatoid arthritis (RA) and healthy controls. Two high density nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA, and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis to determine the patterns of signaling cascades or tissue origin. 44% of patients with ankylosing spondylitis demonstrated a broad autoantibody response, as compared with 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The autoantibody responses in the AS patients were targeted toward connective, skeletal, and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic acid programmable protein arrays constitute a powerful tool to study autoimmune diseases.
22510450 The role of muscarinic acetylcholine receptor type 3 polypeptide (M3RP205-220) antibody in 2012 May BACKGROUND: Sjögren's syndrome (SS) is a chronic autoimmune disorder of unknown cause. Recent studies have shown that antimuscarinic acetylcholine type 3 receptor (M3R) antibodies can be detected in patients with Sjögren's syndrome (SS), but little is known about the diagnostic value of this antibody. OBJECTIVES: To assess the clinical correlations of anti-M3R (muscarinic acetylcholine receptor type 3) polypeptide (M3RP205-220) antibodies in saliva from patients of primary Sjögren's syndrome (pSS). METHODS: Serum samples and unstimulated mixed saliva from 100 patients with SS were collected and examined. Their mean (SD) age was 54.2 (13.4) years, and the mean (SD) disease duration was 6.2 (3.8) years. Serum samples from 40 patients with systemic lupus erythematosus (SLE), 40 with rheumatoid arthritis (RA), and 60 healthy subjects were analysed as controls. All the patients with SS were carefully evaluated according to European and American criteria. A circular M3RP205-220 peptide sequence was synthesized using solid-phase techniques on an applied biosytems peptide synthesizer. The correlation between anti-M3RP205-220 antibodies and clinical manifestations of pSS was analysed. RESULTS: The IgG of anti-M3RP205-220 antibodies was present in 69% of patients with pSS, 27.5% with SLE, 22.5% with RA, and 23.3% of normal saliva donors. The prevalence of anti-M3RP205-220 antibodies in pSS was significantly higher than in SLE, RA, and normal controls. The specificity of anti-M3RP205-220 antibodies in pSS was 75%. The salivary flow rate in the group positive for anti-M3RP205-220 was 436 μl/10 min, compared to a rate of 658 μl/10 min for the negative group (p<0.05). CONCLUSIONS: The anti-M3RP205-220 antibody was detected in most patients with pSS. The presence of the antibody was closely associated with the salivary flow rate. This indicated that it may act as an autoantigen, with a role in the pathogenesis of pSS.
24059900 MRI evaluation of the temporomandibular joints in juvenile rheumatoid arthritis: a retrosp 2011 Dec 30 The purpose of this study was to evaluate the MRI findings of children with rheumatoid arthritis (JRA) affecting the temporomandibular joints (TMJ) and correlate these findings with symptoms. MRI studies of the TMJ in 26 children with a clinical diagnosis of JRA were retrospectively reviewed. All studies included oblique and sagittal T1, T2*, proton density/T2, and coronal T1-weighted images. T1 and proton density/T2-images were repeated with the mouth open. Post contrast sagittal and coronal T1-images were obtained in 19 patients. All studies were done on either 1.5 Tesla or 3.0 Tesla units with dedicated surface coils. By consensus, two radiologists evaluated the studies for abnormal condyles, bone erosions, presence or absence of discs, effusions, contrast enhancement and pannus. Open mouth views were assessed for incomplete or abnormal translation. Clinical records were reviewed to correlate symptoms with MRI findings. Abnormal condyles were seen in 49%. Discs were identifiable in 71%. Abnormal translation was seen in 71% and pannus in 49%. Erosions were seen in 37%, effusions in 24% and contrast enhancement in 50%. Correlation with clinical examination showed that of five asymptomatic patients, three had abnormal translation. Fifteen patients presented joint asymmetry on clinical examination and all showed abnormal translation on MRI. Our findings suggest that abnormal translation and joint enhancement may be the most common MRI findings in JRA patients with TMJ arthritis. Abnormalities may occur even in the absence of symptoms and the most common finding in symptomatic patients is abnormal translation.
21751649 Sjogren's thrombocytopenia. 2011 Feb Primary Sjogren's is a multisystem autoimmune disease which predominantly affects the exocrine glands. pSS may occasionally present in an atypical way which may defy correct diagnosis for a considerable period of time. Clinically important immune-mediated cytopenia (or a combination of cytopenias) may be the first manifestation of an occult SS and have only been rarely described with Sjogren's. This case exemplifies the atypical presentation of pSS and hence should be considered in the differential diagnosis of patients with unexplained cytopenias.