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ID PMID Title PublicationDate abstract
25286515 [Fc-receptor proteins of Streptococcus pyogenes and pathogenesis of post-infection complic 2014 May Phenomenon and mechanism of non-immune binding of immunoglobulins G and A by various emm-genotypes of group A streptococcus and in particular M-family proteins--main factors of pathogenicity of this causative agent of widespread human diseases are examined. The role of these receptor proteins in pathogenesis of post-streptococcal damage of kidneys (glomerules) and heart (myocarditis) are proved. Results of long-term studies that confirm hypothesis of initiating function of Fc-receptor M proteins in genesis of immune inflammation in organ tissues that precede development of glomerulonephritis and myocarditis are provided. According to the basic position, Fc-binding of an immunoglobulin by M proteins initiates production of anti-IgG, immune complexes of various composition and complement activation, deposition of those in tissues results in lymphocyte infiltration and production of pro-inflammatory cytokines. Literature data on the role of Fc-binding proteins in genesis of IgA-nephropathies and rheumatoid factor is also examined. An important role of other factors of the microbe is discussed such as cross-reacting antigens, erythrogenic toxin B, system of streptokinase-plasmin receptor or endostreptosin in post-streptococcal processes in kidneys. Their participation in the process must be mediated by an inflammation reaction in the tissue that is initiated by interaction of immunoglobulins with Fc-binding proteins of the microbe. A novel approach to understanding the nature of this pathology allowed to establish the ability of Fc-fragments of immunoglobulin G to suppress the development of the process.
25396070 Cell-bound complement activation products in systemic lupus erythematosus: comparison with 2014 OBJECTIVE: To compare the performance characteristics of cell-bound complement (C4d) activation products (CBCAPS) on erythrocyte (EC4d) and B cells (BC4d) with antibodies to double-stranded DNA (anti-dsDNA) and complement C3 and C4 in systemic lupus erythematosus (SLE). METHODS: The study enrolled 794 subjects consisting of 304 SLE and a control group consisting of 285 patients with other rheumatic diseases and 205 normal individuals. Anti-dsDNA and other autoantibodies were measured using solid-phase immunoassays while EC4d and BC4d were determined using flow cytometry. Complement proteins were determined using immunoturbidimetry. Disease activity in SLE was determined using a non-serological Systemic Lupus Erythematosus Disease Activity Index SELENA Modification. A two-tiered methodology combining CBCAPS with autoantibodies to cellular and citrullinated antigens was also developed. Statistical analyses used area under receiver operating characteristic curves and calculations of area under the curve (AUC), sensitivity and specificity. RESULTS: AUC for EC4d (0.82±0.02) and BC4d (0.84±0.02) was higher than those yielded by C3 (0.73±0.02) and C4 (0.72±0.02) (p<0.01). AUC for CBCAPS was also higher than the AUC yielded by anti-dsDNA (0.79±0.02), but significance was only achieved for BC4d (p<0.01). The combination of EC4d and BC4d in multivariate testing methodology with anti-dsDNA and autoantibodies to cellular and citrullinated antigens yielded 80% sensitivity for SLE and specificity ranging from 70% (Sjogren's syndrome) to 92% (rheumatoid arthritis) (98% vs. normal). A higher proportion of patients with SLE with higher levels of disease activity tested positive for elevated CBCAPS, reduced complement and anti-dsDNA (p<0.03). CONCLUSIONS: CBCAPS have higher sensitivity than standard complement and anti-dsDNA measurements, and may help with the differential diagnosis of SLE in combination with other autoantibodies.
24060529 Effect of tripterygium glycosides on pulmonary function in adjuvant arthritis rats. 2013 Dec BACKGROUND: Tripterygium is a Chinese herb with immunosuppressive effects and an established history of use in the treatment of rheumatoid arthritis. Previous studies demonstrated that tripterygium glycosides (TPG) alleviated Freund's complete adjuvant (FCA)-induced arthritis. Simultaneously, it has also been observed to impact the adjuvant arthritis (AA) associated with lung injury. In this study, we have investigated whether traditional Chinese medicine could attenuate lung injury induced by AA by observing the effects of TPG on the degree swelling, arthritis index (AI), lung index (LI), pulmonary function, cytokines, and the expression of regulatory T cells (Treg) and Foxp3 in AA rats. METHODS: A total of 48 rats were separated into four groups: normal control (NC), model control (MC), methotrexate (MTX), and TPG groups (12 in each). Except for the rats of NC group, those in the others groups were intracutaneously injected in the right hind limb with 0.1 ml of FCA. The NC and MC groups were treated with physiological saline, and the MTX and TPG groups were treated with MTX and TPG, respectively. Thirty days after administration, the changes in swelling degree, AI, LI, pulmonary function, Treg levels, the ultrastructure of the lung tissue, and the expression of Foxp3 in the lung tissue were observed. RESULTS: Compared with NC group, the level of swelling degree, AI, LI, 1 second average expiratory flow (FEV1/FVC %), the alveolar inflammation integration, tumor necrosis factor alpha (TNF-α), and endothelium-1 (ET-1) in the MC group had significantly increased (p < 0.01). However, the level of forced vital capacity (FVC), 25% vital capacity of the peak expiratory flow (FEF25), 50% vital capacity of the peak expiratory flow (FEF50), 75% vital capacity of the peak expiratory flow (FEF75), maximum mid-expiratory flow (MMF), peak expiratory flow (PEF), interleukin-10 (IL-10), CD4(+) CD25(+) Treg, and Foxp3 had significantly decreased (p < 0.01). LI, the alveolitis score, and ET-1 were found to decrease with TPG treatment. However, the levels of FVC, FEF25, FEF50, FEF75, MMF, PEF, IL-10 in serum, and CD4(+) CD25(+) Treg in peripheral blood had increased. The expressions of Foxp3 protein and mRNA in the lung tissue had also increased in the TPG group. Compared with the MTX group, the pulmonary function had enhanced, the structure of alveolar type II cells had improved, and the expression of the IL-10, Treg, and Foxp3 had elevated. However, the TNF-α and ET-1 levels had reduced as compared to the MTX group. CONCLUSION: The level of paw swelling and AI in the AA rats can be inhibited by TPG. The inflammatory response in lung tissue had also decreased, although there was significant improvement in the pulmonary function. The mechanism that would explain this observation is probably associated with the upregulation of the expression of IL-10, Treg, and Foxp3 and downregulation of the expression of TNF-α and ET-1.
24291002 Sonoporation-mediated transduction of siRNA ameliorated experimental arthritis using 3 MHz 2014 Mar The goal of this feasibility study was to examine whether sonoporation assisted transduction of siRNA could be used to ameliorate arthritis locally. If successful, such approach could provide an alternative treatment for the patients that have or gradually develop adverse response to chemical drugs. Tumor necrosis factor alpha (TNF-α) produced by synovial fibroblasts has an important role in the pathology of rheumatoid arthritis, inducing inflammation and bone destruction. In this study, we injected a mixture of microbubbles and siRNA targeting TNF-α (siTNF) into the articular joints of rats, and transduced siTNF into synovial tissue by exposure to a collimated ultrasound beam, applied through a probe 6mm in diameter with an input frequency of 3.0 MHz, an output intensity of 2.0 W/cm(2) (spatial average temporary peak; SATP), a pulse duty ratio of 50%, and a duration of 1 min. Sonoporation increased skin temperature from 26.8 °C to 27.3 °C, but there were no adverse effect such as burns. The mean level of TNF-α expression in siTNF-treated knee joints was 55% of those in controls. Delivery of siTNF into the knee joints every 3 days (i.e., 7, 10, 13, and 16 days after immunization) by in vivo sonoporation significantly reduced paw swelling on days 20-23 after immunization. Radiographic scores in the siTNF group were 56% of those in the CIA group and 61% of those in the siNeg group. Histological examination showed that the number of TNF-α positive cells was significantly lower in areas of pannus invasion into the ankle joints of siTNF- than of siNeg-treated rats. These results indicate that transduction of siTNF into articular synovium using sonoporation may be an effective local therapy for arthritis.
23452511 Evaluation of the novel folate receptor ligand [18F]fluoro-PEG-folate for macrophage targe 2013 Mar 1 INTRODUCTION: Detection of (subclinical) synovitis is relevant for both early diagnosis and monitoring of therapy of rheumatoid arthritis (RA). Previously, the potential of imaging (sub)clinical arthritis was demonstrated by targeting the translocator protein in activated macrophages using (R)-[11C]PK11195 and positron emission tomography (PET). Images, however, also showed significant peri-articular background activity. The folate receptor (FR)-β is a potential alternative target for imaging activated macrophages. Therefore, the PET tracer [18F]fluoro-PEG-folate was synthesized and evaluated in both in vitro and ex vivo studies using a methylated BSA induced arthritis model. METHODS: [18F]fluoro-PEG-folate was synthesized in a two-step procedure. Relative binding affinities of non-radioactive fluoro-PEG-folate, folic acid and naturally circulating 5-methyltetrahydrofolate (5-Me-THF) to FR were determined using KB cells with high expression of FR. Both in vivo [18F]fluoro-PEG-folate PET and ex vivo tissue distribution studies were performed in arthritic and normal rats and results were compared with those of the established macrophage tracer (R)-[11C]PK11195. RESULTS: [18F]fluoro-PEG-folate was synthesized with a purity >97%, a yield of 300 to 1,700 MBq and a specific activity between 40 and 70 GBq/µmol. Relative in vitro binding affinity for FR of F-PEG-folate was 1.8-fold lower than that of folic acid, but 3-fold higher than that of 5-Me-THF. In the rat model, [18F]fluoro-PEG-folate uptake in arthritic knees was increased compared with both contralateral knees and knees of normal rats. Uptake in arthritic knees could be blocked by an excess of glucosamine-folate, consistent with [18F]fluoro-PEG-folate being specifically bound to FR. Arthritic knee-to-bone and arthritic knee-to-blood ratios of [18F]fluoro-PEG-folate were increased compared with those of (R)-[11C]PK11195. Reduction of 5-Me-THF levels in rat plasma to those mimicking human levels increased absolute [18F]fluoro-PEG-folate uptake in arthritic joints, but without improving target-to-background ratios. CONCLUSIONS: The novel PET tracer [18F]fluoro-PEG-folate, designed to target FR on activated macrophages provided improved contrast in a rat model of arthritis compared with the accepted macrophage tracer (R)-[11C]PK11195. These results warrant further exploration of [18F]fluoro-PEG-folate as a putative PET tracer for imaging (sub)clinical arthritis in RA patients.
25264706 Regulation of osteoclastogenesis through Tim-3: possible involvement of the Tim-3/galectin 2014 Nov Galectins are a unique family of lectins bearing one or two carbohydrate recognition domains (CRDs) that have the ability to bind molecules with β-galactoside-containing carbohydrates. It has been shown that galectins regulate not only cell growth and differentiation but also immune responses, as well as inflammation. Galectin-9, a tandem repeat type of galectin, was originally identified as a chemotactic factor for eosinophils, and is also involved in the regulatory process of inflammation. Here, we examined the involvement of galectin-9 and its receptor, T-cell immunoglobulin- and mucin-domain-containing molecule 3 (Tim-3), in the control of osteoclastogenesis and inflammatory bone destruction. Expression of Tim-3 was detected in osteoclasts and its mononuclear precursors in vivo and in vitro. Galectin-9 markedly inhibited osteoclastogenesis as evaluated in osteoclast precursor cell line RAW-D cells and primary bone marrow cells of mice and rats. The inhibitory effects of galectin-9 on osteoclastogenesis was negated by the addition of β-lactose, an antagonist for galectin binding, suggesting that the inhibitory effect of galectin-9 was mediated through CRD. When galectin-9 was injected into rats with adjuvant-induced arthritis, marked suppression of bone destruction was observed. Inflammatory bone destruction could be efficiently ameliorated by controlling the Tim-3/galectin-9 system in rheumatoid arthritis.
24582615 Swertiamarin attenuates inflammation mediators via modulating NF-κB/I κB and JAK2/STAT3 2014 Jun 2 Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease that leads to pannus formation followed by severe joint destruction, characterized by synovial hyperplasia, inflammation and angiogenesis. Swertiamarin is a secoiridoid glycoside that is used as an anti-inflammatory compound, mainly found in Enicostema axillare (Lam) A. Raynal, a medicinal plant used in Indian system of traditional medicine. In the present study, the effect of swertiamarin was evlauated in experimental adjuvant arthritis animal model by the estimation of biochemical (paw thickness, lysosomal enzymes, and urinary degradative products) parameters, proinflammatory cytokines and enzymes along with histopathological and radiographic observations. The proteins of phosphorylated NF-κB/IκB and JAK2/STAT3 transcription factors were also quantified from experimental animals as well as LPS induced RAW 264.7 macrophage cells. In in silico analysis, swertiamarin was docked with proinflammatory enzymes to confirm its potential. The administration of swertiamarin (2, 5, 10mg/kg bw) significantly (P⩽0.05) inhibited the levels of paw thickness, lysosomal enzymes and increased the body weight of experimental animals in a dose dependent manner. In molecular analysis, the treatment decreased the release of proinflammatory cytokines (IL1, TNF, IL-6) and proangiogenic enzymes (MMPs, iNOS, PGE2, PPARγ and COX-2); and also significantly (P⩽0.05) increased the levels of antiinflammatory proteins (IL-10, IL-4) when compared to the disease groups. The swertiamarin treatment significantly (P⩽0.05) inhibited the release of NF-κB p65, p-IκBα, p-JAK2 and p-STAT3 signaling proteins levels on both experimental animals and LPS induced cells. Histopathological and radiological analysis evidenced the curative effect of swertiamarin on bone destruction. The docking studies of swertiamarin on proinflammatory enzymes supported the results from the in vivo experiments. Thus the swertiamarin inhibited the development of arthritis by modulating NF-κB/IκB and JAK2/STAT3 signaling. These findings suggested that swertiamarin acted as an anti-rheumatic agent.
23549599 Therapeutic effects of NK-HDAC-1, a novel histone deacetylase inhibitor, on collagen-induc 2013 Aug The purpose of this study is to investigate the therapeutic effects of a novel histone deacetylase inhibitor (HDACi), NK-HDAC-1, on collagen-induced arthritis (CIA) and pathogenic fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). The proliferation and apoptosis of FLSs treated with NK-HDAC-1 were evaluated by flow cytometry and fluorescence staining. The effect of NK-HDAC-1 treatment on pro-inflammatory cytokine production was determined by ELISA. CIA was established in DBA/1 mice, and NK-HDAC-1 or vehicle was administered daily after the onset of arthritis. Clinical and histological scores were calculated to assess the therapeutic efficacy of NK-HDAC-1. NK-HDAC-1 significantly inhibited the proliferation of FLSs through cell cycle arrest at the G2/M checkpoint and enhanced apoptosis of FLSs. The activity of caspases was increased during NK-HDAC-1 treatment. IL-6 production by FLSs was also suppressed by NK-HDAC-1. Furthermore, the oral administration of NK-HDAC-1 significantly enhanced synoviocyte apoptosis in vivo and inhibited CIA progression. Compared with subcroylanilide hydroxamic acid which exhibited moderate prophylactic efficacy, NK-HDAC-1 demonstrated therapeutic efficacy in CIA. NK-HDAC-1 is a novel HDACi that may ameliorate inflammatory arthritis by regulating the activation, apoptosis, and inflammatory responses of FLSs. This is the first study to support that NK-HDAC-1 may be a potential therapeutic agent for RA.
23541482 Cardiovascular disease in autoimmune rheumatic diseases. 2013 Aug Various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis, spondyloarthritis, vasculitis and systemic lupus erythematosus, are associated with premature atherosclerosis. However, premature atherosclerosis has not been uniformly observed in systemic sclerosis. Furthermore, although experimental models of atherosclerosis support the role of antiphospholipid antibodies in atherosclerosis, there is no clear evidence of premature atherosclerosis in antiphospholipid syndrome (APA). Ischemic events in APA are more likely to be caused by pro-thrombotic state than by enhanced atherosclerosis. Cardiovascular disease (CVD) in ARDs is caused by traditional and non-traditional risk factors. Besides other factors, inflammation and immunologic abnormalities, the quantity and quality of lipoproteins, hypertension, insulin resistance/hyperglycemia, obesity and underweight, presence of platelets bearing complement protein C4d, reduced number and function of endothelial progenitor cells, apoptosis of endothelial cells, epigenetic mechanisms, renal disease, periodontal disease, depression, hyperuricemia, hypothyroidism, sleep apnea and vitamin D deficiency may contribute to the premature CVD. Although most research has focused on systemic inflammation, vascular inflammation may play a crucial role in the premature CVD in ARDs. It may be involved in the development and destabilization of both atherosclerotic lesions and of aortic aneurysms (a known complication of ARDs). Inflammation in subintimal vascular and perivascular layers appears to frequently occur in CVD, with a higher frequency in ARD than in non-ARD patients. It is possible that this inflammation is caused by infections and/or autoimmunity, which might have consequences for treatment. Importantly, drugs targeting immunologic factors participating in the subintimal inflammation (e.g., T- and B-cells) might have a protective effect on CVD. Interestingly, vasa vasorum and cardiovascular adipose tissue may play an important role in atherogenesis. Inflammation and complement depositions in the vessel wall are likely to contribute to vascular stiffness. Based on biopsy findings, also inflammation in the myocardium and small vessels may contribute to premature CVD in ARDs (cardiac ischemia and heart failure). There is an enormous need for an improved CVD prevention in ARDs. Studies examining the effect of DMARDs/biologics on vascular inflammation and CV risk are warranted.
25379815 How good is the coverage and how accurate are exposure data in the Swedish Biologics Regis 2015 OBJECTIVES: To assess the coverage of the Swedish Biologics Register (Anti-Rheumatic Therapy in Sweden, ARTIS) across indications, and the accuracy of the registered information on treatment with biologics. METHOD: Through cross-reference of ARTIS to almost complete national health registers on prescriptions (adalimumab and etanercept), outpatient visits, and death/residency during 2008-2010, we assessed: the treatment coverage of ARTIS for each treatment indication, the validity of the registered start and stop dates, ARTIS treatments with no corresponding drug dispensations, and the accuracy of the registered information on concomitant anti-rheumatic therapies. RESULTS: According to the national health registers, 3945 individuals with a spondyloarthropathy (SpA) and 8032 patients with rheumatoid arthritis (RA) had filled at least one adalimumab or etanercept prescription during the study period. Of these, 86% of those with SpAs and 95% of patients with RA were also found in ARTIS with the corresponding treatment. Tumour necrosis factor (TNF) inhibitor prescriptions had been filled by 95% of patients between the ARTIS start and stop dates (allowing a 90-day window). More than 60 days before and more than 60 days after the registered start date in ARTIS, 5% and 4% respectively of patients had filled their first TNF inhibitor prescription. More than 90 days after the registered stop date in ARTIS, 8% of patients had filled one or more TNF inhibitor prescriptions. CONCLUSIONS: We observed a high coverage and accuracy of ARTIS data on biologics exposure, for both SpAs and RA. The combination of data from clinical registers such as ARTIS with data from national health registers offers a high quality measurement of actual treatment.
24935412 Methods of assessment of tophus and bone erosions in gout using dual-energy CT: reproducib 2015 Apr This study aims to evaluate the intraobserver and interobserver reproducibility of the tophus urate volume, erosion volume, and the erosion score measurements in patients with gout by using dual-energy CT (DECT) scans comparing their bone erosion volumes against bone erosion scores and also to determine a valid measure of joint destruction in chronic gout. Sixty-six subjects underwent DECT scans of the hands or feet. Two independent observers measured the tophus urate volumes and bone erosion volumes using automated volume assessment software and the erosion scores based on the rheumatoid arthritis magnetic resonance imaging score (RAMRIS). The intraobserver and interobserver reproducibility were analyzed by intraclass correlation coefficient (ICC) and limits of agreements analysis. The relationship between erosion volumes and erosion scores was analyzed. The intraobserver and interobserver ICC for tophus urate volume measurements (n = 636) were 1.000 (95 % confidence interval (95 % CI) 1.000 to 1.000) and 1.000 (95 % CI 1.000 to 1.000), 0.999 (0.999, 0.999) and 0.999 (0.999, 0.999) for bone erosion volumes (n = 350), 0.937 (0.928, 0.946) and 0.899 (0.883, 0.912) for erosion scores (n = 350). Strong positive correlations were demonstrated between individual erosion volumes and scores (r s = 0.914, p < 0.001) as well as total erosion volume and score per patient (r = 0.838-0.867, p < 0.001). This study demonstrated a high reproducibility of tophus urate volumes, erosion volumes, and erosion score measurements using DECT. Erosion volumes show to be a more direct and accurate method to evaluate bone erosion compared with erosion score, strongly supporting it as a superior and standard measure of structural joint damage in gout.
24886659 Network analysis identifies protein clusters of functional importance in juvenile idiopath 2014 May 8 INTRODUCTION: Our objective was to utilise network analysis to identify protein clusters of greatest potential functional relevance in the pathogenesis of oligoarticular and rheumatoid factor negative (RF-ve) polyarticular juvenile idiopathic arthritis (JIA). METHODS: JIA genetic association data were used to build an interactome network model in BioGRID 3.2.99. The top 10% of this protein:protein JIA Interactome was used to generate a minimal essential network (MEN). Reactome FI Cytoscape 2.83 Plugin and the Disease Association Protein-Protein Link Evaluator (Dapple) algorithm were used to assess the functionality of the biological pathways within the MEN and to statistically rank the proteins. JIA gene expression data were integrated with the MEN and clusters of functionally important proteins derived using MCODE. RESULTS: A JIA interactome of 2,479 proteins was built from 348 JIA associated genes. The MEN, representing the most functionally related components of the network, comprised of seven clusters, with distinct functional characteristics. Four gene expression datasets from peripheral blood mononuclear cells (PBMC), neutrophils and synovial fluid monocytes, were mapped onto the MEN and a list of genes enriched for functional significance identified. This analysis revealed the genes of greatest potential functional importance to be PTPN2 and STAT1 for oligoarticular JIA and KSR1 for RF-ve polyarticular JIA. Clusters of 23 and 14 related proteins were derived for oligoarticular and RF-ve polyarticular JIA respectively. CONCLUSIONS: This first report of the application of network biology to JIA, integrating genetic association findings and gene expression data, has prioritised protein clusters for functional validation and identified new pathways for targeted pharmacological intervention.
25562082 Epigenetics and periodontal disease: hope to tame the untameable. 2014 Epigenetics means gene expression alterations which occur due to the biochemical changes of the nucleotides modifying structure of DNA rather than the changes in the genetic code itself as in case of mutations. The epigenome, consisting of chromatin and its modifications, acts as a link between the inherited genome and the changes imposed by the environment. Over the past decade, there has been mounting evidence suggestive of associations between epigenetic modifications and various human conditions such as aging, and most common human diseases viz. cancer, cardiovascular diseases, diabetes, rheumatoid arthritis, HIV etc and the clearest evidence as the central mechanism for common multifactorial diseases, has been identified with the factors involved in the inflammatory response. Periodontal disease, basically an immune-inflammatory affliction, being a multifactorial complex disease, owing to its high prevalence, chronicity and wide ranging systemic effects, essentially calls for a better comprehension of the underlying disease mechanisms, so as to develop and decipher the novel methodologies to combat this disease. The current paper aims to visualize periodontal disease from an epigenetic perspective, featuring the contemporary evidence supported literature and tends to explore the possibilities to find some explanations for perio-systemic health links, individualized and improvised diagnostic tools for earlier detection and ways to halt the disease and help regeneration and reconstruction of the lost periodontal attachment apparatus with the biology based approaches.
27708904 Spontaneous patellar tendon rupture in a case followed up for diagnosis of systemic lupus 2014 Dec Spontaneous patellar tendon rupture is a rare condition that usually occurs secondary to conditions, such as rheumatoid arthritis, systemic lupus erythematosus (SLE), and use of steroids and fluoroquinolones. This paper presents a full-thickness patellar tendon rupture detected with magnetic resonance imaging, which was performed due to pain and swelling that started spontaneously on the front side of the left knee without a history of any trauma, of a 35-year-old male patient who had been followed up for a diagnosis of SLE for approximately 4 months and who had started taking methylprednisolone 4 mg/day 4 months prior, used it for 1 month, and then stopped using it. In patients who are followed up for a diagnosis of SLE, it should be kept in mind that there is a risk of developing a spontaneous tendon rupture secondary to chronic inflammation and use of corticosteroids.
24493331 Abatacept as a successful therapy for myositis—a case-based review. 2015 Mar Only limited evidence exists on the therapeutic potential of biologic agents in the treatment of myositis. We present a brief review of the literature on off-label experiences of biologic agents in myositis, with a special interest in abatacept. Rituximab has been indicated to be beneficial and well tolerated in one large randomized controlled trial and many smaller studies. Initial data on tumour necrosis factor (TNF) inhibitors are conflicting. There are only a few case reports and mechanistic studies on the treatment of myositis with other biologics, including alemtuzumab, anakinra, tocilizumab and abatacept. We report a patient with severe myositis overlap syndrome, manifesting also as rheumatoid arthritis, peripheral vasculitis and interstitial lung disease. Her myositis was refractory to many conventional and biologic therapies but was well controlled with abatacept. This suggests that abatacept might be a beneficial option for the treatment of refractory myositis and that clinical trials are needed to further investigate its efficacy.
24377380 Extensor tendon rupture caused by instability of the ulnar head with an osteoarthritic dis 2013 Dec 30 INTRODUCTION: Although spontaneous extensor tendon rupture often occurs in association with rheumatoid arthritis, extensor tendon rupture associated with osteoarthritis of the distal radioulnar joint has been rarely reported. CASE PRESENTATION: We present the case of a 74-year-old Asian woman with a fourth and fifth extensor tendon rupture caused by instability of the ulnar head associated with an osteoarthritic distal radioulnar joint. Intraoperative findings showed that the cause of the dorsal capsular perforation and extensor tendon rupture was mechanical friction with the unstable ulnar head, which had no osteophytes or roughness. After tendon transfer and resection of the ulnar head, our patient can extend her ring and little fingers without difficulty for her daily activities. CONCLUSIONS: When a patient with osteoarthritic distal radioulnar joint has instability of the ulnar head and the 'scallop sign' on radiography, physicians should consider the possibility of extensor tendon rupture as a complication.
23993305 Peripheral ulcerative keratitis in association with sarcoidosis. 2013 Dec Peripheral ulcerative keratitis (PUK) is a sight-threatening condition characterized by an epithelial defect, crescent-shaped stromal inflammation, and progressive stromal thinning. Peripheral ulcerative keratitis as a purely inflammatory entity is most commonly associated with collagen vascular diseases, including rheumatoid arthritis, polyarteritis nodosa, Wegener granulomatosis, systemic lupus erythematosus, and relapsing polychondritis. PUK can also be associated with infectious and inflammatory conditions such as hepatitis, syphilis, herpes simplex keratitis, fungal keratitis, Mooren ulcer, and marginal keratitis. We describe a case report of PUK associated with the inflammatory condition of sarcoidosis.
23808094 Ehrlichiosis presenting with toxic shock-like syndrome and secondary hemophagocytic lympho 2013 Jun Human monocytotropic ehrlichios is a tick borne illness caused by Ehrlichia chaffeensis. Ehrlichiosis presenting with septic shock and severe azotemia is rare, and may be seen in immunocompromised individuals. We present a case of ehrlichia induced toxic shock like syndrome in a patient with rheumatoid arthritis on disease modifying agents. He also had oliguric renal failure requiring dialysis on presentation and later found to have Hemophagocytic Lymphohistiocytosis secondary to severe ehrlichia sepsis.
23652189 [Single nucleotide polymorphisms (SNPs): functional implications of regulatory-SNP (rSNP) 2013 Mar Single nucleotide polymorphisms (SNPs) represent to the genetics variant most common founded in the human genome. These polymorphisms have a wide distribution and can found in any region of gene or mRNA, the SNPs that have functional implications on the levels of gene expression are called regulatory SNPs (rSNPs), while those that affect translation, splicing, efficiency to enhance or inhibit the alternative, mRNA stability and protein function (without altering its structure), they are called structural RNA SNPs (srSNPs). Several studies have identified to these polymorphisms associated with different common diseases e.g. hypertension, obesity, rheumatoid arthritis and coronary artery disease. The aim of this review is to discuss the functional implication of rSNPs and srSNPs in the common diseases.
23265898 Novel small molecule protein arginine deiminase 4 (PAD4) inhibitors. 2013 Feb 1 Protein arginin deaminase 4 (PAD4) is a calcium dependent enzyme which catalyses the conversion of peptidyl-arginine into peptidyl-citrulline and is implicated in several diseases such as rheumatoid arthritis (RA) and cancer. Herein we report the discovery of novel small-molecule, non peptidic PAD4 inhibitors incorporating primary/secondary guanidine moieties.