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ID PMID Title PublicationDate abstract
18461501 Plasmacytoid dendritic cells and interferon-alpha in Aicardi-Goutières syndrome. 2007 Dec In Aicardi-Goutières syndrome (AGS), as in systemic lupus erythematosus (SLE) and Sjögren's syndrome, an increased level of interferon alpha (IFN-alpha) is involved in the pathogenesis of the disease. In SLE and Sjögren's syndrome, cytokine production originates in plasmacytoid dendritic cells (pDCs) under the influence of immune complexes formed by DNA and RNA from improperly removed apoptotic or necrotic cells, together with IgG autoantibodies. We studied the role of soluble factors in the serum or cerebrospinal fluid (CSF) of AGS patients and their capacity to stimulate pDCs to produce IFN-alpha. Our findings show that, in contrast to SLE, there is no decrease in the number of circulating pDCs in AGS patients. Secondly, unlike the autoantibodies in the serum of patients with SLE or Sjögren's syndrome, there is no increased frequency of antinuclear antibodies (ANA) or other soluble factors inducing IFN-alpha from pDCs. These data indicate that the origin of IFN-alpha in AGS is different from that in the autoimmune diseases tested.
16633930 Expansion of large granular lymphocytes following Pseudomonas infection in a patient with 2006 We report a patient who had a 4-year history of adult-onset Still's disease (AOSD) and showed a prominent increase in large granular lymphocytes (LGL) when she developed severe Pseudomonas conjunctivitis due to Pseudomonas aeruginosa, skin eruptions, liver damage, and abnormal findings in coagulation studies, without any evidence of active viral activation, hemophagocytosis, or malignancies. The increased LGL cells were CD3(+)CD8(+), and disappeared promptly after the administration of antibiotics combined with prednisolone, with subsequent stabilization of her general condition.
16567554 Dental plaque pH and micro-organisms during hyposalivation. 2006 Apr We have previously reported that minor gland and whole saliva flow rates and salivary proteins showed differences in individuals with primary Sjögren's syndrome or head and neck radiation therapy, compared with controls (Eliasson et al., 2005). We now hypothesize that pH and number of acidogenic micro-organisms in dental plaque as well as saliva buffering capacity also differ in these individuals. Plaque pH was measured by the microtouch method up to 60 min after a sucrose rinse. Plaque collected from the same sites was analyzed for counts of total and acidic micro-organisms. Compared with their controls, the irradiated group but not the Sjögren's syndrome group displayed significantly lower plaque pH, increased numbers of lactobacilli and Candida species, as well as reduced buffering capacity. Stepwise regression tests suggested that the buccal minor-salivary-gland secretion rate in the test groups and counts of mutans streptococci in the controls were of significant importance for dental plaque pH.
17714766 Primary Sjogren's syndrome: current and prospective therapies. 2008 Apr OBJECTIVE: To summarize data on existing and experimental therapies for primary Sjogren's syndrome (pSS), referring both to sicca syndrome and to other systemic disease manifestations. METHODS: Relevant English and non-English articles acquired through Medline were reviewed. RESULTS: pSS usually has a benign clinical course, centered on sicca features and general musculoskeletal manifestations, and is managed symptomatically. However, a subset of patients develops more severe extraglandular disease that warrants close monitoring and aggressive treatment. For dry eyes and mouth, nonpharmacologic measures to preserve secretions, and tear and saliva substitutes, offer some symptomatic relief. Muscarinic agonists and topical cyclosporine yield well-documented improvement in ocular sicca features. Although traditional antirheumatic drugs are used empirically for polyarthritis and other Sjogren's symptoms, their efficacy in pSS overall and as disease-modifying agents is limited. For the potential severe, nonexocrine manifestations complicating pSS, standard high-dose immunosuppression is used. Among the biologic agents already examined in pSS, those targeting tumor necrosis factor (TNF)-alpha failed to demonstrate significant benefit. Nonetheless, rituximab and other B-cell-depleting therapies appear promising. CONCLUSIONS: Treatment of pSS patients with severe extraglandular disease should differ from that of patients with predominantly sicca features and/or general muscoloskeletal manifestations. pSS treatment is mainly symptomatic, primarily directed against sicca complaints. The traditional anti-rheumatic agents show limited efficacy in the systemic process and use of systemic TNF-alpha inhibitors has been very disappointing. B cell depleting treatments and other newer biologic therapies appear more promising.
16889286 Ibuprofen-induced fever in Sjogren's syndrome. 2006 A 68-year-old woman with a medical history significant for Sjögren syndrome and leukocytoclastic vasculitis of small vessels presented to the emergency department with chills, malaise, a temperature of 39 degrees C, nausea, vomiting, and hypotension. Fifteen minutes earlier she had taken ibuprofen for flu-like symptoms. She was treated with a perfusion of intravenous saline, paracetamol, and ciprofloxacin with improvement 24 hours later. Three months later, she had a similar episode, without hypotension. An oral challenge test with ibuprofen in the hospital produced the same symptoms 3 hours after the last dose. She was treated with metamizole and paracetamol and was asymptomatic the next day. This is the first report of a febrile reaction to ibuprofen in a patient with Sjogren's syndrome.
18930990 Neuropsychiatric syndromes in patients with systemic lupus erythematosus and primary Sjög 2009 Oct OBJECTIVES: To compare the prevalence and pattern of neuropsychiatric (NP) syndromes observed in systemic lupus erythematosus (SLE) to patients with Primary Sjögren syndrome (PSS) using the American College of Rheumatology (ACR) criteria for the 19 NP syndromes seen in SLE. METHODS: A population-based study was conducted including 68 patients with SLE (mean (SD) age 43.8 (13.6) years) and 72 with PSS (age 57.8 (13.0) years). Specialists in internal medicine, neurology and neuropsychology performed standardised examinations. Cerebral MRI scans and neurophysiological studies were performed in all patients. RESULTS: Similar prevalences in SLE and PSS were observed for headaches (87% vs 78%, p = 0.165), cognitive dysfunction (46% vs 50%, p = 0.273), mood disorders (26% vs 33%, p = 0.376), anxiety disorders (12% vs 4%, p = 0.095), cranial neuropathy (1% vs 4%, p = 0.339) and seizure disorders (7% vs 3%, p = 0.208). Cerebrovascular disease was more common in SLE than PSS (12% vs 3%, p = 0.049); but mononeuropathy (0% vs 8%, p = 0.015) and polyneuropathy (18% vs 56%, p<0.001) were less common in SLE than PSS. Other syndromes were rare or absent in both patient groups. CONCLUSIONS: Headache, cognitive dysfunction and mood disorders are common in both diseases, but otherwise there are distinct differences in NP involvement, with cerebrovascular diseases more prevalent in SLE and neuropathies more common in PSS. This indicates that some NP disease mechanisms are shared while others differ between the two diseases.
18272178 The fellowship of the RING: the RING-B-box linker region interacts with the RING in TRIM21 2008 Mar 21 Ro52 is a major autoantigen that is targeted in the autoimmune disease Sjögren syndrome and belongs to the tripartite motif (TRIM) protein family. Disease-related antigenic epitopes are mainly found in the coiled-coil domain of Ro52, but one such epitope is located in the Zn(2+)-binding region, which comprises an N-terminal RING followed by a B-box, separated by a approximately 40-residue linker peptide. In the present study, we extend the structural, biophysical, and immunological knowledge of this RING-B-box linker (RBL) by employing an array of methods. Our bioinformatic investigations show that the RBL sequence motif is unique to TRIM proteins and can be classified into three distinct subtypes. The RBL regions of all three subtypes are as conserved as their known flanking domains, and all are predicted to comprise an amphipathic helix. This helix formation is confirmed by circular dichroism spectroscopy and is dependent on the presence of the RING. Immunological studies show that the RBL is part of a conformation-dependent epitope, and its antigenicity is likewise dependent on a structured RING domain. Recombinant Ro52 RING-RBL exists as a monomer in vitro, and binding of two Zn(2+) increases its stability. Regions stabilized by Zn(2+) binding are identified by limited proteolysis and matrix-assisted laser desorption/ionization mass spectrometry. Furthermore, the residues of the RING and linker that interact with each other are identified by analysis of protection patterns, which, together with bioinformatic and biophysical data, enabled us to propose a structural model of the RING-RBL based on modeling and docking experiments. Sequence similarities and evolutionary sequence patterns suggest that the results obtained from Ro52 are extendable to the entire TRIM protein family.
17900780 Protective effects of Pycnogenol on carbon tetrachloride-induced hepatotoxicity in Sprague 2008 Jan Oxidative damage is implicated in the pathogenesis of various liver injuries. In the present study the ability of Pycnogenol (PYC) as an antioxidant to protect against CCl4-induced oxidative stress and hepatotoxicity in rats was investigated. Four experimental groups of six rats each were constructed: a vehicle control group received the respective vehicles (distilled water and corn oil) only; a CCl4 group received a 14-day repeated intraperitoneal (i.p.) dose of distilled water and then a single oral dose of CCl4 at 1.25 ml/kg; and the CCl4&PYC 10 and CCl4&PYC 20 groups received a 14-day repeated i.p. dose of PYC 10 and 20 mg/kg, respectively, and then a single oral dose of CCl4 at 1.25 ml/kg. Hepatotoxicity was assessed 24 h after the CCl4 treatment by measurement of serum aminotransferase (AST) and alanine aminotransferase (ALT) activities, hepatic malondialdehyde (MDA) and glutathione (GSH) concentrations, and catalase, superoxide dismutase (SOD), and glutathione-S-transferase (GST) activities. The results were confirmed histopathologically. The single oral dose of CCl4 produced significantly elevated levels of serum AST and ALT activities. Histopathological examinations showed extensive liver injuries, characterized by extensive hepatocellular degeneration/necrosis, fatty changes, inflammatory cell infiltration, congestion, and sinusoidal dilatation. In addition, an increased MDA concentration and decreased GSH, catalase, SOD, and GST were observed in the hepatic tissues. On the contrary, PYC treatment prior to the administration of CCl4 significantly prevented the CCl4-induced hepatotoxicity, including the elevation of serum AST and ALT activities and histopathological hepatic lesions, in a dose-dependent manner. Moreover, MDA and GSH levels and catalase, SOD, and GST activities in hepatic tissues were not affected by administration of CCl4, indicating that the pretreatment of PYC efficiently protects against CCl4-induced oxidative damage in rats. The results indicate that PYC has a protective effect against acute hepatotoxicity induced by the administration of CCl4 in rats, and that the hepatoprotective effects of PYC may be due to both the inhibition of lipid peroxidation and the increase of antioxidant activity.
19030778 Comparison of anti-rheumatic effects of local RNAi-based therapy in collagen induced arthr 2009 RNA interference (RNAi) provides a powerful means of sequence-specific gene silencing. Several studies show that RNAi may provide promising strategies to treat human diseases by suppressing disease responsible genes in vivo. In locomotor diseases, the progression of collagen-induced arthritis (CIA) is suppressed by tumor necrosis factor-alpha (TNF-alpha)-specific small interfering RNA (siRNA) delivered into the joint. The aim of this study, is to compare the effects of intraarticularly administered siRNAs targeting TNF-alpha, interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and receptor activator of NF-kappaB ligand (RANKL) on CIA in rats. We confirmed that the silencing effects of siRNA duplexes specific for rat TNF-alpha, IL-1beta, IL-6 and RANKL in vitro. Each siRNA was also delivered into the knee joint of CIA rats by the in vivo electroporation method 7, 10, 13 and 16 days after immunization with collagen. Local delivery of TNF-alpha or IL-1beta-specific siRNA ameliorated CIA in rats effectively at the gross morphological, radiographical and histological evaluations. Our results suggested that TNF-alpha and IL-1beta were the cytokines to be targeted in the joint for the treatment of rheumatoid arthritis. The in vivo siRNA transfection method may be useful for selection of target molecules to be silenced for treatment of joint diseases.
18713142 Mesenchymal stem cells overexpressing interleukin-10 attenuate collagen-induced arthritis 2008 Aug Mesenchymal stem cells (MSCs) have the inherent ability to migrate to multiple organs and to exert immunosuppressive activity. The aim of this study was to investigate the anti-arthritogenic effects of interleukin (IL)-10-transduced MSCs (IL-10-MSC) on the development of inflammatory arthritis. DBA/1 mice were immunized with type II collagen (CII) to induce inflammatory arthritis and then injected weekly three times with IL-10-MSCs 21 days after primary immunization. Control mice received vehicle or MSCs alone. Serum anti-CII antibody and T cell response to CII were determined. The results showed that cultured IL-10-MSCs were able to secrete high amounts of IL-10 in vitro. Injection of IL-10-MSCs decreased the severity of arthritis significantly. However, there was no difference in arthritis severity between mice treated with MSC and vehicle alone. Anti-CII antibody titres in the sera and T cell proliferative response to CII in lymph node cells were decreased significantly in mice treated with IL-10-MSCs compared with vehicle-treated mice. Serum IL-6 level was also decreased by the administration of IL-10-MSCs. In contrast, spleen cells of IL-10-MSC-treated mice produced higher amounts of IL-4 than those of control mice. Interestingly, although not as potent as IL-10-MSCs, injection of naive MSCs alone decreased serum levels of IL-6 and anti-CII antibody, while increasing IL-4 production from cultured splenic cells. Taken together, systemic administration of genetically modified MSCs overexpressing IL-10 inhibits experimental arthritis not only by suppressing autoimmune response to CII but also by regulating cytokine production, and thus would be a new strategy for treating rheumatoid arthritis.
16520943 CC chemokine receptor (CCR)-2 prevents arthritis development following infection by Mycoba 2006 Jun The host factors that influence autoimmune arthritides such as rheumatoid arthritis have not been fully elucidated. We previously found that genetic inactivation of CC chemokine receptor 2 (CCR2) in the arthritis-prone DBA/1j mouse strain significantly increases the susceptibility of this strain to autoimmune arthritis induced by immunization with collagen type II (CII) and complete Freund's adjuvant (CFA). Here, we show that following intradermal infection with Mycobacterium avium, a similar arthritis phenotype was detected in Ccr2-null mice in the DBA/1j, but not in the BALB/c background. The failure to develop arthritis in Ccr2-null BALB/c mice occurred in the face of high bacterial burdens and low interferon gamma (IFNgamma) production. By contrast, Ccr2-null DBA/1j mice had low bacterial burdens, produced normal amounts of IFNgamma, and had high titers of autoantibodies against CII. Thus, the Ccr2-null state in an arthritic-prone genetic background leads to increased arthritis susceptibility following infectious (M. avium) and noninfectious (CII/CFA) challenges. Because CCR2 serves as a negative regulator of murine arthritis, caution might need to be exercised while testing CCR2 blockers in human arthritis or other diseases. These findings also indicate that Ccr2-null DBA/1j mice might serve as a valuable model system to uncover the immunological determinants of arthritis and to test novel antiarthritic agents.
17530712 Activation of invariant natural killer T cells by synthetic glycolipid ligands suppresses 2007 Jun OBJECTIVE: Stimulation of invariant natural killer T (iNKT) cells with SGL-S23, a novel synthetic glycolipid analog of alpha-galactosylceramide with an elongated sphingosine chain, has been shown to strongly suppress K/BxN serum transfer arthritis. This study was designed to evaluate the protective effects of SGL-S23 in an effector phase of arthritis. METHODS: To induce arthritis, C57BL/6 mice were injected with 150 mul of serum from K/BxN mice (KRN TCR-transgenic mice crossed with nonobese diabetic mice). Subsequently, synthetic glycolipid ligands were administered intraperitoneally twice, either 3 times starting on day 0 (the day of K/BxN serum injection) or twice starting on day 3. Neutralizing antibody against interferon-gamma (IFNgamma) interleukin-4 (IL-4), IL-10, or transforming growth factor beta was administered 4 hours before injection of SGL-S23. Recombinant IFNgamma was administered subcutaneously every day. The severity of arthritis was monitored using a macroscopic scoring system. Cytokine production and plasma histamine levels were measured by enzyme-linked immunosorbent assay. RESULTS: SGL-S23 strongly suppressed K/BxN serum transfer arthritis by inhibiting inflammatory cell infiltration and subsequent destruction of cartilage and bone. The inhibitory effect mediated by SGL-S23 was abolished by neutralization of IFNgamma. Systemic administration of IFNgamma prevented the development of inflammatory arthritis. Histamine release was suppressed by administration of SGL-S23 or IFNgamma. Degranulated mast cells in the synovium were significantly reduced in SGL-S23-treated mice, suggesting that suppression of mast cell activation contributed to the inhibition of arthritis. CONCLUSION: These findings suggest that activation of iNKT cells with glycolipid ligands holds promise with regard to the treatment of autoimmune diseases such as rheumatoid arthritis. SGL-S23 has clinical benefit over alpha-galactosylceramide since it induces a weaker cytokine production response in iNKT cells, therefore reducing potential side effects caused by excessive cytokine release.
16704745 Human, viral or mutant human IL-10 expressed after local adenovirus-mediated gene transfer 2006 IL-10 is a Th2 cytokine important for inhibiting cell-mediated immunity while promoting humoral responses. Human IL-10 (hIL-10) has anti-inflammatory, immunosuppressive as well as immunostimulatory characteristics, whereas viral IL-10 (vIL-10), a homologue of hIL-10 encoded by Epstein Barr virus (EBV), lacks several immunostimulatory functions. The immunostimulatory characteristic of hIL-10 has been attributed to a single amino acid, isoleucine at position 87, which in vIL-10 is alanine. A mutant hIL-10 in which isoleucine has been substituted (mut.hIL-10) is biologically active with only immunosuppressive, but not immunostimulatory, functions, making it a potentially superior therapeutic for inflammatory diseases. To compare the efficacy of mut.hIL-10 with hIL-10 and vIL-10 in blocking the progression of rheumatoid arthritis, we used replication defective adenoviral vectors to deliver intra-articularly the gene encoding hIL-10, vIL-10 or mut.hIL-10 to antigen-induced arthritic (AIA) knee joints in rabbits. Intra-articular expression of hIL-10, vIL-10, and mut.hIL-10 resulted in significant improvement of the pathology in the treated joints to similar levels. These observed changes included a significant reduction in intra-articular leukocytosis and the degree of synovitis, as well as normalization of cartilage matrix metabolism. Our results suggest that hIL-10, vIL-10, and mut.hIL-10 are all equally therapeutic in the rabbit AIA model for treating disease pathology.
21172233 Pneumonia due to Nocardia cyriacigeorgica in a patient with Crohn's disease treated with i 2008 Dec Infliximab, an anti-tumor necrosis factor α (TNF-α) antibody, is useful in the treatment of rheumatoid arthritis, Crohn's disease etc. It has been related to increases in the rate of several infections. We present the case of a 53-year-old woman diagnosed with community-acquired pneumonia due to Nocardia cyriacigeorgica who was taking infliximab, azathioprine and prednisone for Crohn's disease.
17349384 [Elbow arthroscopy: intra-articular pathologies.]. 2006 Nov Elbow arthroscopy has become to be the most useful tool for the treatment of many intra-articular affections of the elbow. Radiological statement is necessary including plain radiographs and CT or MR arthrography before performing arthroscopy. Loose bodies are the more frequent indication, they are often related with an other intra-articular pathology. The others indications for an elbow arthroscopy can be, osteochondritis dissecans, synovial fringe, synovitis especially rheumatoid arthritis and arthritic elbow. The treatment of this different pathologies is discribe keeping in mind the potential risks especially neurological.
19034292 A pair of twins born after maternal exposure to leflunomide. 2008 Dec Leflunomide is a drug used in rheumatoid arthritis with teratogenic and fetotoxic effects. Clinical data on human pregnancies are limited to a few case reports without detailed information whether the mothers did have a washout procedure as suggested by the manufacturer or what type of malformation the offspring showed. We report on a set of twins born after maternal exposure to leflunomide who had a largely normal neonatal outcome, providing information about the washout procedure and the blood level of the active metabolite.
17565884 [Atherosclerosis in inflammatory diseases]. 2007 May 19 The recognition that inflammation is a hallmark of atherosclerotic disease and its complications has led to a series of studies reporting high prevalence of atherosclerosis in chronic inflammatory diseases. Indeed, chronic immune diseases, such as systemic lupus erythematosus and rheumatoid arthritis, are associated with proinflammation, accelerated atherosclerosis and increased incidence of cardiovascular disease. Since the susceptibility towards cardiovascular events cannot be explained by classical risk factors, disease-specific pathways have been put forward as additional risk factors, potentially important for future prevention and treatment of atherosclerosis associated with chronic inflammatory diseases.
16945247 Update on rheumatologic mimics of fibromyalgia. 2006 Oct Fibromyalgia is a common disorder of diffuse musculoskeletal pain. Several rheumatic diseases can mimic fibromyalgia, and a clinician would not want to miss these diagnoses because of their potential long-term sequelae, such as progressive joint damage or life- or organ-threatening disease if they remain untreated. This paper discusses the typical clinical presentations of selected rheumatic diseases (systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, polymyalgia rheumatica, and osteoarthritis) then highlights the key features in history, laboratory testing, and radiographic imaging that aid the clinician in differentiating between fibromyalgia and these rheumatic diseases.
18331834 TRPV1 mediates cell death in rat synovial fibroblasts through calcium entry-dependent ROS 2008 May 16 Synoviocyte hyperplasia is critical for rheumatoid arthritis, therefore, potentially an important target for therapeutics. It was found in this work that a TRPV1 agonist capsaicin, and acidic solution (pH 5.5) induced increases in cytosolic calcium concentration ([Ca(2+)](c)) and reactive oxygen species (ROS) production in synoviocytes isolated from a rat model of collagen-induced arthritis. The increases in both [Ca(2+)](c) and ROS production were completely abolished in calcium-free buffer or by a TRPV1 antagonist capsazepine. Further experiments revealed that capsaicin and pH 5.5 solution caused mitochondrial membrane depolarization and reduction in cell viability; such effects were inhibited by capsazepine, or the NAD(P)H oxidase inhibitor diphenylene iodonium. Both capsaicin and pH 5.5 buffer induced apoptosis as shown by nuclear condensation and fragmentation. Furthermore, RT-PCR readily detected TRPV1 mRNA expression in the isolated synoviocytes. Taken together, these data indicated that TRPV1 activation triggered synoviocyte death by [Ca(2+)](c) elevation, ROS production, and mitochondrial membrane depolarization.
18688188 [Case of systemic lupus erythematosus occurring after induced abortion and drug eruption]. 2008 Jul We describe a19 year-old woman who was diagnosed as systemic lupus erythematosus (SLE) after abortion. She had taken anti-convulsants for epilepsy since she was 8 years old. Induced abortion surgery was performed at six weeks in her pregnancy. She showed pyrexia and a general rash 2 days after the abortion. She was introduced to our hospital because the administration of antibiotics was not effective. Since the anti-convulsants had been changed after pregnancy, we returned to those administered before pregnancy and followed her up. Her eruption improved, but she became aware of thirstiness and dry eye. She was diagnosed as Sjögren syndrome by ophthalmologic examination, lip biopsy, and elevation of an anti-SS-A antibody and an anti-SS-B antibody in the serum. Since we could not rule out SLE because of the low concentration of complement activity in blood, we followed her up carefully by checking serum markers of SLE. Protein urine developed after the improvement of the eruption 2 weeks later. Low complement activity was recognized and double stranded (ds)-DNA antibody became positive. In addition to these findings, she had an episode of hypersensitivity to sunlight and was therefore diagnosed as SLE. Since induced abortion and drug eruption might be associated with the onset of SLE, the case is thought to be a valuable from the view point of understanding the mechanism of SLE onset.