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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
16582688 An update on osteoarthritis therapeutics. 2006 May PURPOSE OF REVIEW: This review addresses recent major developments in symptomatic therapy and the principles of disease modification in osteoarthritis. It emphasizes issues that are of importance to the practicing clinician at a time when researchers in the field are trying to improve ways not only to provide symptomatic relief but also to slow disease progression. RECENT FINDINGS: The past year has led to a reassessment of the role of cyclo-oxygenase-2 inhibitors in osteoarthritis therapy and has yielded new information on nutriceuticals such as glucosamine. The relative efficacy of intra-articular injections of agents such as corticosteroid and hyaluronic acid preparations has been assessed. In addition, reports on trials of potentially disease-modifying agents for osteoarthritis have been published. SUMMARY: Because the therapeutic options have been reduced over the past year and the role of nutritional supplements remains unclear, the clinician is faced with a need to reassess osteoarthritis therapy. Although no practical disease-modifying agent for osteoarthritis has been identified, reports such as the recent doxycycline trial reviewed herein provide hope that continued research will soon yield a therapeutic model similar to that used in rheumatoid arthritis, for which some therapeutic agents achieve disease modification and other agents can be added as needed for symptomatic relief.
22855957 Antinuclear Antibody, Rheumatoid Factor, and Cyclic-Citrullinated Peptide Tests for Evalua 2007 In response to a request from the public, a systematic review assessed the test performances of antinuclear antibody (ANA), rheumatoid factor (RF), and cyclic-citrullinated peptide (CCP) for pediatric systemic lupus erythematosus (pSLE) and juvenile idiopathic arthritis (JIA) among children (≤18 years) with undiagnosed musculoskeletal (MSK) pain. The systematic review included 28 clinical studies published from January 1960 to January 2010 and also characterized the prevalence and etiology of MSK pain in children. This summary is provided to inform discussions of options with patients and to assist in decisionmaking along with consideration of the values and preferences of patients and their caregivers; it should not be construed to represent clinical recommendations or guidelines. The full report is available at www.effectivehealthcare.ahrq.gov/anatest.cfm.
18415770 Incidence of thromboembolic events in patients with primary Sjögren's syndrome. 2008 Mar Primary Sjögren's syndrome (pSS) is a connective tissue disease with symptoms and serological findings often overlapping with systemic lupus erythematosus (SLE) (1). Thromboembolic events are common in SLE but not in pSS (2)(3). However, case reports have described pSS patients who developed fulminant multiorgan disease due to thrombotic diathesis 4, and we have presented a case with acute catastrophic anti-phospholipid syndrome (APS) in a pSS patient (5). In this study we wanted to examine the incidence of thromboembolic episodes and relate these to the presence of autoantibodies and coagulation abnormalities in 90 pSS patients during a 4.6-year follow-up.
18201372 B-cell activating factor of the tumour necrosis factor family expression in blood monocyte 2008 Feb We investigated B-cell activating factor of the tumour necrosis factor family (BAFF) level in peripheral blood mononuclear cells (PBMCs), monocytes and T cells from patients with primary Sjögren's syndrome (pSS) and controls both ex vivo and in vitro after cytokine stimulation. PBMCs, monocytes and T cells were isolated from 15 patients with pSS and 17 controls. Cells were cultured alone or with interferon (IFN)alpha, IFNgamma and interleukin 10 (IL-10). T cells were stimulated with phytohaemagglutin and anti-CD3. BAFF protein was assessed by enzyme-linked immunosorbent assay. Ex vivo, no difference was observed in BAFF mRNA level in PBMCs and monocytes from patients and controls. Blood monocytes were the main cell type secreting BAFF both in patients and controls. In vitro, after IFNalpha stimulation, BAFF mRNA level was significantly higher in cells from patients than from controls (63.8 versus 20.7, P = 0.03). T cells from patients secreted a higher level of BAFF protein than those from healthy donor cells (17.4 versus 2.9 pg/ml, respectively, P = 0.04) but at a lower level than that from monocytes. Stimulation of T cells did not change BAFF secretion level. The induction of Th17 cells showed no increased BAFF expression. In conclusion, similar to epithelial cells, blood monocytes in patients with pSS show increased production of BAFF under IFNalpha, which confirms the involvement of IFNalpha in pSS. BAFF expression is also increased in blood T cells of such patients, independently of T-cell stimulation.
17212735 Combined factor VIII and IX inhibitors in a non-haemophilic patient: successful treatment 2007 Jan A rare case of a patient with Sjogren syndrome and spontaneously acquired inhibitors of both factor VIII and factor IX is reported. Complete remission was obtained by means of immunosuppressive drugs.
19091760 Frankincense: systematic review. 2008 Dec 17 OBJECTIVE: To assess evidence from randomised clinical trials about the effectiveness of extracts of Boswellia serrata (frankincense). DESIGN: Systematic review. DATA SOURCES: Electronic searches on Medline, Embase, Cinahl, Amed, and Cochrane Library. Hand searches of conference proceedings, bibliographies, and departmental files. REVIEW METHODS: All randomised clinical trials of B serrata extract as a treatment for any human medical condition were included and studies of B serrata preparations combined with other ingredients were excluded. Titles and abstracts of all retrieved articles were read and hard copies of all relevant articles were obtained. Selection of studies, data extraction and validation were done by the author. The Jadad score was used to evaluate the methodological quality of all included trials. RESULTS: Of 47 potentially relevant studies, seven met all inclusion criteria (five placebo controlled, two with active controls). The included trials related to asthma, rheumatoid arthritis, Crohn's disease, osteoarthritis, and collagenous colitis. Results of all trials indicated that B serrata extracts were clinically effective. Three studies were of good methodological quality. No serious safety issues were noted. CONCLUSIONS: The evidence for the effectiveness of B serrata extracts is encouraging but not compelling.
19082529 Successful treatment of refractory polymyositis with the immunosuppressant mizoribine: cas 2009 Feb We describe a patient who presented with polymyositis with anti-Jo-1 antibodies at 18 years after the onset of rheumatoid arthritis and was successfully treated with the immunosuppressive drug mizoribine at the time of exacerbation. She had developed diabetes mellitus, cerebral infarction, and myocardial infarction after high-dose steroid therapy was initiated. Therefore, an immunosuppressant was preferred as the second-line agent. Treatment with 150 mg/day of mizoribine and 8 mg/day of prednisolone resulted in eventual normalization of muscle enzyme levels. Mizoribine is a purine antimetabolite that inhibits T cell activation/proliferation and B cell proliferation. The potential efficacy of mizoribine for polymyositis was suggested by this case.
19082420 Vascular basement membrane components in angiogenesis--an act of balance. 2008 Dec 14 Angiogenesis is crucial in the progression of a number of pathological conditions, such as diabetic retinopathy, rheumatoid arthritis, psoriasis, and cancer. In contrast to vessels in healthy tissues, the vasculature in these pathologies is highly unstable, constantly dissolving and renewing. Characteristically, vessels in pathologies have discontinuous basement membrane (BM) coverage. The consequences of shifts in BM density and composition are still relatively unknown. Several studies have illustrated that partial loss of the vascular BM during development results in the widening of vessels. This has been suggested to be a result of reduced mechanical resistance to the force inflicted by the blood pressure. However, recent data indicate that depletion of BM laminins (LMs) leads to enlarged vessels even in the absence of cardiac activity and blood pressure. A key question is whether single BM components or fragments thereof play distinct roles in the angiogenic process, or if it is the balance between the different components of the BM that guides the morphology of the new vessel.
19038101 [Th17 cells, a novel proinflammatory effector CD4 T cell population]. 2008 Nov After more than 20 years of hegemony, the Th1-Th2 paradigm was recently shaken by the discovery of a novel population of CD4 effector T cells, the Th17 cells. Th17 effector cells produce IL-17 and IL-22 and thus have pro-inflammatory properties notably favoring neutrophils recruitment and thus control of extracellular bacteria mainly at the epithelium surface. Th17 cells appear also as the major inducer of organ specific autoimmune pathologies such as EAE or rheumatoid arthritis, a function previously attributed to Th1 effector cells. The discovery of Th17 cells further supports the notion that effector CD4 T cells responses are diverse in vivo and that fine tuning of these different effector cells is critical to maintain tissue integrity.
19007665 Chapter 8. Noninvasive imaging of blood vessels. 2008 Angiogenesis is a key component in several major clinical conditions including cancer, diabetic retinopathy, rheumatoid arthritis, endometriosis and psoriasis. All these diseases could be managed much more effectively if their angiogenic capacities were somehow curtailed. Hence there is great interest in developing a fuller understanding of angiogenesis and designing agents to suppress, guide, and normalize this process. Although much has been learned from in vitro methods, the perspective is limited because angiogenesis depends on active blood flow and a variety of circulating precursor cells provided by the intact host. Therefore, noninvasive in vivo methods that provide information over days and weeks are needed. Accordingly, the rodent dorsal skinfold tissue window chamber facilitates the imaging of new vessels around implanted cells, around an injury, or around a simple device impregnated with growth factors. Tissue oxygen levels can be measured during the course of angiogenesis using a window chamber that is also fitted with a miniature multiple electrode sensor. The present review describes window chamber methods and hardware, the measurement of oxygen, and the introduction into the chamber of tumors, growth factors, and organs to induce angiogenesis. The application of multiphoton microscopy to intravital imaging is discussed, along with a description of how to modify a standard brightfield or fluorescence microscope for multiphoton imaging of window chamber microvessels.
18566383 B cell chemoattractant CXCL13 is preferentially expressed by human Th17 cell clones. 2008 Jul 1 Th 17 cells represent a novel subset of CD4+ T cells that have a protective effect against extracellular microbes, while they are also responsible for autoimmune disorders in mice. However, the protein expression profile of Th17 cells remains to be clarified. In this study, we report an effective method to establish human allo-reactive Th17 cell clones and demonstrate that human Th17, but not Th1 or Th2, cells express B cell chemoattractant CXCL13, by using DNA chips, RT-PCR, and ELISA. Such a pattern was also the case in Candida albicans-specific Th17 clones and synovial fluid specimens obtained from patients with rheumatoid arthritis. The biological implication of this finding is discussed.
18508550 B lymphocytes--chief players and therapeutic targets in autoimmune diseases. 2008 May 1 For some time, B cells have been considered as passive actors, exclusively depending on T cell conductors that provide them with instructions to engage in antibody secretion. With further investigation, however, it became evident that B cells can exert a number of antibody-independent functions, capturing and concentrating antigen for presentation, producing cytokines, influencing T cell and dendritic cell responses, contributing distinct functions during the immune response, affecting lymphoid tissue structures, and, even participating in tissue repair. Because of their multiples functions, B cells are currently recognized to play a key role in a variety of antibody-, and T cell-mediated autoimmune diseases, including lupus, rheumatoid arthritis, type-1 diabetes and multiple sclerosis. This recent insight led to novel immuno-intervention strategies that target B cells, with beneficial effects in patients. While such novel therapeutic bio-drugs are being introduced into the clinical arena, research intensifies in order to identify novel targets and strategies whose ultimate goal is to knock out specifically pathogenic B cells, and to amplify the numbers and the activity of cells endowed with regulatory functions.
18489346 Update on peptidylarginine deiminases and deimination in skin physiology and severe human 2007 Jun Deimination (or citrullination) is a recently described post-translational modification, but its consequences are not yet well understood. It is catalysed by peptidylarginine deiminases (PADs). These enzymes transform arginyl residues involved in a peptidyl link into citrullyl residues in a calcium-dependent manner. Several PAD substrates have already been identified like filaggrin and keratins K1 and K10 in the epidermis, trichohyalin in hair follicles, but also ubiquitous proteins like histones. PADs act in a large panel of physiological functions as cellular differentiation or gene regulation. It has been suggested that deimination plays a role in many major diseases such as rheumatoid arthritis, multiple sclerosis, Alzheimer's disease and psoriasis. Five human genes (PADIs), encoding five highly conserved paralogous enzymes (PAD1-4 and 6), have been characterized. These genes are clustered in a single locus, at 1p35-36 in man. Only PAD1-3 are expressed in human epidermis. PADs seem to be controlled at transcriptional, translational and activity levels and they present particular substrate specificities. In this review, we shall discuss these main biochemical, genetic and functional aspects of PADs together with their pathophysiological implications.
18446013 [Pathogenic analysis of chronic inflammatory disease based on the clinical results by IL-6 2008 Apr Every clinician knows the elevation of acute phase proteins at the inflammatory status, but nobody knows the CRP or SAA induction mechanism on inflammation, in which a lot of cytokines or chemokines are activated. Induction mechanism of CRP and SAA is analyzed based on the result of the normalization of serum CRP or SAA in rheumatoid arthritis by the IL-6 blocking therapy with a humanized anti IL-6 receptor antibody. Ultimately, IL-6 is a pivotal cytokine among IL-6, IL-1 and TNF-a in induction of CRP and SAA in hepatocyte. Furthermore, activation of STAT3, a transcriptional factor under IL-6 signal transduction pathway, is critical on the expression of these mRNAs. Based on this mechanism, the depression of CRP and SAA induction could be explained by the IL-6 blockage both in vitro and in vivo. Therefore, IL-6 blocking therapy may elucidate the pathogenic significance of IL-6 in chronic inflammatory disease.
18418695 The role of cell death in the pathogenesis of autoimmune disease: HMGB1 and microparticles 2008 Cell death is critical to normal homeostasis, although this process, when increased aberrantly, can lead to the production of pro-inflammatory mediators promoting autoimmunity. Two novel intercellular mediators of inflammation generated during cell death are high mobility group box 1 (HMGB1) protein and microparticles (MPs). HMGB1 is a nuclear protein that functions in transcription when inside the nucleus but takes on pro-inflammatory properties when released during cell death. Microparticles are small, membrane-bound structures that extrude from cells when they die and contain cell surface proteins and nuclear material from their parent cells. MPs circulate widely throughout the vasculature and mediate long-distance communication between cells. Both MPs and HMGB1 have been implicated in the pathogenesis of a broad spectrum of inflammatory diseases, including the prototypic autoimmune conditions systemic lupus erythematosus and rheumatoid arthritis. Given their range of activity and association with active disease, both structures may prove to be targets for effective therapy in these and other disorders.
21794546 [Contribution of animal models to the study and treatment of systemic autoimmune disease]. 2008 Mar Animal models of autoimmune diseases, either spontaneous or induced, have been very useful tools to investigate the mechanisms involved in the pathogenesis of human autoimmune diseases as well as in the design of new therapeutic strategies for their treatment. The development of biotechnology and molecular biology resulted in the production of transgenic animals overexpressing or lacking a given protein. As a result of this technology, a great number of animal models of human diseases have been developed in recent years. A further evolution in transgenic methodology allows the selective control of gene expression in a particular organ or tissue at desired time points during embryonic or postnatal development. In the present article the authors discuss the advantages and inconveniences of animal models and describe the most frequently employed models in the study of 4 rheumatologic syndromes with an autoimmune origin: rheumatoid arthritis, systemic lupus erythematosus, scleroderma, and spondiloarthritis.
18284247 Biocatalyzed cross-coupling of sinomenine and guaiacol by Antrodiella semisupina. 2008 Mar 20 In search of more potent derivatives of sinomenine (1), a clinically available natural alkaloid for the treatment of rheumatoid arthritis (RA), biocatalyzed cross-coupling of sinomenine and guaiacol (2) by Antrodiella semisupina, provided two unique C-C coupled (3 and 4) and one C-O linked (5) novel metabolites. The structures of the metabolites were elucidated by means of MS, 2D NMR techniques and X-ray analysis. 4 exhibited more potent inhibitory activity on IL-6 production than 1 in human synovial sarcoma cell (SW982), and 5 stimulated IL-6 production.
20477590 Targeting signaling pathways with small molecules to treat autoimmune disorders. 2008 Jan Chronic activation of immune responses, mediated by inflammatory mediators and involving different effector cells of the innate and acquired immune system characterizes autoimmune disorders, such as rheumatoid arthritis, inflammatory bowel disease, psoriasis and septic shock syndrome. MAPKs are crucial intracellular mediators of inflammation. MAPK inhibitors are attractive anti-inflammatory drugs, because they are capable of reducing the synthesis of inflammation mediators at multiple levels and are effective in blocking proinflammatory cytokine signaling. Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway converts cytokine signals into genomic responses regulating proliferation and differentiation of the immune cells. JAK inhibitors are a new class of immunomodulatory agents with immunosuppressive, anti-inflammatory and antiallergic properties. This review discusses the rationale behind current strategies of targeting MAPK and JAK/STAT signaling pathways, and the overall effects of signal transduction inhibitors in animal models of inflammatory disorders. Signal transduction inhibitors are small molecules that can be administered orally, and initial results of clinical trials have shown clinical benefits in patients with chronic inflammatory disorders.
18051107 Automatic segmentation of blood vessels from dynamic MRI datasets. 2007 In this paper we present an approach for blood vessel segmentation from dynamic contrast-enhanced MRI datasets of the hand joints acquired from patients with active rheumatoid arthritis. Exclusion of the blood vessels is needed for accurate visualisation of the activation events and objective evaluation of the degree of inflammation. The segmentation technique is based on statistical modelling motivated by the physiological properties of the individual tissues, such as speed of uptake and concentration of the contrast agent; it incorporates Markov random field probabilistic framework and principal component analysis. The algorithm was tested on 60 temporal slices and has shown promising results.
17976864 Investigations concerning the COX/5-LOX inhibiting and hydroxyl radical scavenging potenci 2008 Jun The aim of this study was to investigate 4,5-diaryl isoselenazoles as multiple target non-steroidal anti-inflammatory drugs (MTNSAIDs) which can intervene into the inflammatory processes via different mechanisms of action creating a new class of compounds. Here we describe the synthesis of COX/LOX inhibitors which additionally reduce the level of reactive oxygen species, such as hydroxyl radicals which are well known for supporting inflammation processes in Parkinson's disease, Alzheimer's disease and rheumatoid arthritis.