Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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19254958 | Th1/Th17 polarization and acquisition of an arthritogenic phenotype in arthritis-susceptib | 2009 May | Proteoglycan (PG) aggrecan-induced arthritis (PGIA) is a murine model of rheumatoid arthritis (RA). Although BALB/c and DBA/2 mice share the same MHC (H-2d) haplotype, the BALB/c strain is susceptible to PGIA, while DBA/2 mice are resistant. Therefore, these two inbred mouse strains provide an opportunity to study arthritis susceptibility factors excluding the effects of MHC-associated genetic components. The goal of this study was to monitor changes in the cellular composition and activation state following intra-peritoneal (i.p.) immunization to induce PGIA; additionally, we sought to identify new susceptibility factors by comparing PG-induced immune responses in BALB/c and DBA/2 mice. Upon i.p. PG injection, resident naive B1 cells are replaced by both T cells and conventional B cells in the peritoneum of BALB/c mice. These peritoneal T cells produce IFNgamma and IL-17, cytokines shown to be important in RA and corresponding arthritis models. Moreover, peritoneal cells can adoptively transfer PGIA to SCID mice, demonstrating their arthritogenic properties. Our results indicate that repeatedly injected antigen leads to the recruitment and activation of immune cells in the peritoneum; these cells then trigger the effector phase of the disease. The migration and activation of T(h)1/T(h)17 cells in the peritoneal cavity in response to PG immunization, which did not occur in the arthritis-resistant DBA/2 strain, may be critical factors of arthritis susceptibility in BALB/c mice. | |
19688702 | Potential predisposition for nasal septal perforation with methotrexate use: report of 2 c | 2009 Aug | Methotrexate is a dihydrofolate reductase inhibitor with application both as a chemotherapeutic agent and as a disease-modifying antirheumatic drug. Although its ability to inhibit cellular proliferation is a desired effect in its role as an antineoplastic agent, this property may also hinder normal physiologic regeneration of the nasal epithelium. This effect may predispose patients to septal cartilage ischemia, necrosis and, eventually, perforation. We report 2 cases of septal perforations in the setting of prolonged methotrexate use and present a literature review. Patient 1 is an 8-year-old boy with juvenile rheumatoid arthritis managed with weekly methotrexate who developed a 4-mm septal perforation with an unremarkable biopsy. This was closed with a mucosal advancement flap without incident. Patient 2 is an 11-year-old boy with non-Hodgkin lymphoma treated with methotrexate. His examination was significant for a large perforation of the dorsocaudal septum. A biopsy was negative for malignancy in this patient. Repair has been deferred-initially for chemotherapy and currently for treatment relapse. We hypothesize that prolonged use of methotrexate alters the balance between physiologic desquamation and epithelial regeneration. This imbalance may promote septal ischemia and predispose patients to the development of septal perforations. | |
20889598 | Systematic review of MRI, ultrasound, and scintigraphy as outcome measures for structural | 2011 Jan | OBJECTIVE: validated imaging outcome tools to assess response to therapies in a single joint are required. Our aim was to review the published literature to ascertain the responsiveness of novel imaging techniques as outcome measures in interventional therapeutic studies of knee arthritis. METHODS: an Ovid Medline search was performed for original articles in English that used imaging techniques to assess response at the knee joint to therapy in osteoarthritis, rheumatoid arthritis, and psoriatic arthritis. Changes in response to therapy were assessed with regard to both internal and external responsiveness. RESULTS: in the studies that presented appropriate statistical data to allow responsiveness to be assessed, MRI was generally found to be internally responsive to pathologies imaged, and externally responsive, referenced against both other imaging modalities and biochemical biomarkers of arthritis. Ultrasonography was found to demonstrate internal responsiveness with regard to synovial thickness, effusion size, and popliteal cyst size. External responsiveness was demonstrated against several referenced health status measures. Scintigraphy was found to be externally responsive in the majority of studies, with internal responsiveness demonstrated in 1 study. CONCLUSION: while the imaging techniques appear to be responsive from the data we present, further inspection reveals that interpreting the responsiveness of imaging techniques was difficult, largely because of a lack of standardization of image acquisition, definitions of pathology, and scoring systems. Refined pathological definitions and scoring systems are required to enable the development of valid and responsive tools for interventional clinical trials. | |
20454829 | Inhibition of acid-sensing ion channels in articular chondrocytes by amiloride attenuates | 2010 Nov | OBJECTIVE: The aim of this study was to examine whether drugs such as amiloride that block acid sensing ion channels (ASICs) could attenuate articular cartilage destruction in adjuvant-induced arthritis (AA). METHODS: Articular chondrocytes were isolated from the normal rats, and intracellular calcium ([Ca(2+)]i) was analyzed with laser scanning confocal microscopy. The cell injury was analyzed with lactate dehydrogenase release assay and electron microscopy. Amiloride or phosphate buffered saline was administered daily to AA rats for 1 week from the time of arthritis onset. Morphology of the articular cartilage was examined by hematoxylin and eosin staining, and Mankin score was calculated. The expression level of type II collagen (COII) and aggrecan mRNA and proteins in the articular cartilage was evaluated by real-time PCR and Western blotting, respectively. RESULTS: The rapid decrease in extracellular pH (6.0) induced a conspicuous increase in [Ca(2+)]i in the articular chondrocytes. Amiloride reduced this increase in [Ca(2+)]i, and inhibited acid-induced articular chondrocyte injury. Amiloride significantly decreased Mankin scores in the articular cartilage in AA rats. COII and aggrecan mRNA and protein expression in the articular cartilage was significantly increased by amiloride. CONCLUSION: These findings represent some experimental evidence of a potential role for ASICs in the pathogenesis of articular cartilage destruction in rheumatoid arthritis. | |
19288987 | Use of complementary and alternative medicine among patients with arthritis. | 2009 Apr | INTRODUCTION: Previous studies suggest that people with arthritis have high rates of using complementary and alternative medicine (CAM) approaches for managing their arthritis, in addition to conventional treatments such as prescription medications. However, little is known about the use of CAM by diagnosis, or which forms of CAM are most frequently used by people with arthritis. This study was designed to provide detailed information about use of CAM for symptoms associated with arthritis in patients followed in primary care and specialty clinics in North Carolina. METHODS: Using a cross-sectional design, we drew our sample from primary care (n = 1,077) and specialist (n = 1,063) physician offices. Summary statistics were used to calculate differences within and between diagnostic groups, practice settings, and other characteristics. Logistic regression models clustered at the site level were used to determine the effect of patient characteristics on ever and current use of 9 CAM categories and an overall category of "any use." RESULTS: Most of the participants followed by specialists (90.5%) and a slightly smaller percentage of those in the primary care sample (82.8%) had tried at least 1 complementary therapy for arthritis symptoms. Participants with fibromyalgia used complementary therapies more often than those with rheumatoid arthritis, osteoarthritis, or chronic joint symptoms. More than 50% of patients in both samples used over-the-counter topical pain relievers, more than 25% used meditation or drew on religious or spiritual beliefs, and more than 19% used a chiropractor. Women and participants with higher levels of education were more likely to report current use of alternative therapies. CONCLUSION: Most arthritis patients in both primary care and specialty settings have used CAM for their arthritis symptoms. Health care providers (especially musculoskeletal specialists) should discuss these therapies with all arthritis patients. | |
19265134 | Antigen-specific suppression of inflammatory arthritis using liposomes. | 2009 Mar 15 | Existing therapies for rheumatoid arthritis and other autoimmune diseases are not Ag specific, which increases the likelihood of systemic toxicity. We show that egg phosphatidylcholine liposomes loaded with Ag (OVA or methylated BSA) and a lipophilic NF-kappaB inhibitor (curcumin, quercetin, or Bay11-7082) suppress preexisting immune responses in an Ag-specific manner. We injected loaded liposomes into mice primed with Ag or into mice suffering from Ag-induced inflammatory arthritis. The liposomes targeted APCs in situ, suppressing the cells' responsiveness to NF-kappaB and inducing Ag-specific FoxP3(+) regulatory T cells. This regulatory mechanism suppressed effector T cell responses and the clinical signs of full-blown Ag-induced arthritis. Thus, liposomes encapsulate Ags and NF-kappaB inhibitors stably and efficiently and could be readily adapted to deliver Ags and inhibitors for Ag-specific suppression of other autoimmune and allergic diseases. | |
21251450 | Metabolic comorbidities and psoriasis. | 2010 | Psoriasis is a chronic inflammatory, immune-mediated skin disease, which affects 2%-3% of the population worldwide. Chronic plaque psoriasis is frequently associated with metabolic diseases including diabetes, obesity, dyslipidemia, metabolic syndrome and nonalcoholic fatty liver disease. Although the causal relationship between metabolic comorbidities and psoriasis has not yet been completely proven, it appears that shared genetic links, common environmental factors and/or common inflammatory pathways may underlie the development of psoriasis and comorbidities. The presence of comorbidities has important implications in the global approach to patients with psoriasis. Traditional systemic anti-psoriatic agents could negatively affect cardio-metabolic comorbidities, and may have important interactions with drugs commonly used by psoriatic patients. In contrast, the recent findings that the risk of myocardial infarction is reduced in patients with rheumatoid arthritis who respond to anti-TNF-α therapy compared to non-responders, supports the hypothesis that the anti-inflammatory effect of TNF-α blockers might reduce the cardiovascular risk potentially also in psoriasis patients. Finally, patients with moderate to severe psoriasis should be treated promptly and effectively, and should be encouraged to drastically correct their modifiable cardiovascular risk factors, in particular obesity and smoking habit. | |
20662051 | Specific antibody protection of the extracellular cartilage matrix against collagen antibo | 2010 Nov | OBJECTIVE: The type II collagen (CII)-specific monoclonal antibodies (mAb) M2139 and CIIC1 induce arthritis in vivo and degrade bovine cartilage explants in vitro, whereas mAb CIIF4 is nonarthritogenic and prevents arthritis development when given in combination with M2139 and CIIC1. To determine the nature of the protective capacity of CIIF4 antibody, we examined the effects of adding CIIF4 to cartilage explants cultured in vitro with M2139 and CIIC1. METHODS: Bovine cartilage explants were cultured in the presence of M2139 and CIIC1, with or without CIIF4. Histologic changes were examined, and chemical changes to collagens and proteoglycans were assessed by Fourier transform infrared microspectroscopy (FTIRM). Fresh cartilage and cartilage that had been freeze-thawed to kill chondrocytes cultured with or without the addition of GM6001, a broad-spectrum inhibitor of matrix metalloproteinases (MMPs), were compared using FTIRM analysis. RESULTS: M2139 and CIIC1 caused progressive degradation of the cartilage surface and loss of CII, even in the absence of viable chondrocytes. CIIF4 did not cause cartilage damage, and when given with the arthritogenic mAb, it prevented their damage and permitted matrix regeneration, a process that required viable chondrocytes. Inhibition of MMP activity reduced cartilage damage but did not mimic the effects of CIIF4. CONCLUSION: CII-reactive antibodies can cause cartilage damage or can be protective in vivo and in vitro, depending on their epitope specificity. Since CII antibodies of similar specificity also occur in rheumatoid arthritis in humans, more detailed studies should unravel the regulatory mechanisms operating at the effector level of arthritis pathogenesis. | |
19795010 | Gout--current diagnosis and treatment. | 2009 Aug | BACKGROUND: Because of the changing dietary habits of an aging population, hyperuricemia is frequently found in combination with other metabolic disorders. Longstanding elevation of the serum uric acid level can lead to the deposition of monosodium urate crystals, causing gout (arthritis, urate nephropathy, tophi). In Germany, the prevalence of gouty arthritis is estimated at 1.4%, higher than that of rheumatoid arthritis. There are no German guidelines to date for the treatment of gout. Its current treatment is based largely on expert opinion. METHODS: Selective literature review on the diagnosis and treatment of gout. RESULTS AND CONCLUSIONS: Asymptomatic hyperuricemia is generally not an indication for pharmacological intervention to lower the uric acid level. When gout is clinically manifest, however, acute treatment of gouty arthritis should be followed by determination of the cause of hyperuricemia, and long-term treatment to lower the uric acid level is usually necessary. The goal of treatment is to diminish the body's stores of uric acid crystal deposits (the intrinsic uric acid pool) and thereby to prevent the inflammatory processes that they cause, which lead to structural alterations. In the long term, serum uric acid levels should be kept below 360 micromol/L (6 mg/dL). The available medications for this purpose are allopurinol and various uricosuric agents, e.g., benzbromarone. There is good evidence to support the treatment of gouty attacks by the timely, short-term use of non-steroidal anti-inflammatory drugs (NSAID), colchicine, and glucocorticosteroids. | |
19433626 | Adaptive peripheral immune response increases proliferation of neural precursor cells in t | 2009 Sep | To understand the link between peripheral immune activation and neuronal precursor biology, we investigated the effect of T-cell activation on adult hippocampal neurogenesis in female C57Bl/6 mice. A peripheral adaptive immune response triggered by adjuvant-induced rheumatoid arthritis (2 microg/microl methylated BSA) or staphylococcus enterotoxin B (EC(50) of 0.25 microg/ml per 20 g body weight) was associated with a transient increase in hippocampal precursor cell proliferation and neurogenesis as assessed by immunohistochemistry and confocal microscopy. Both treatments were paralleled by an increase in corticosterone levels in the hippocampus 1- to 2-fold over the physiological amount measured by quantitative radioimmunoassay. In contrast, intraperitoneal administration of the innate immune response activator lipopolysaccaride (EC(50) of 0.5 microg/ml per 20 g body weight) led to a chronic 5-fold increase of hippocampal glucocorticoid levels and a decrease of adult neurogenesis. In vitro exposure of murine neuronal progenitor cells to corticosterone triggered either cell death at high (1.5 nM) or proliferation at low (0.25 nM) concentrations. This effect could be blocked using a viral vector system expressing a transdomain of the glucocorticoid receptor. We suggest an evolutionary relevant communication route for the brain to respond to environmental stressors like inflammation mediated by glucocorticoid levels in the hippocampus. | |
19707402 | Challenges in the management of juvenile idiopathic arthritis with etanercept. | 2009 | Biologic agents have been designed with the help of immunological studies to target particular areas of the immune system which are thought to play a role in the pathogenesis of disease. Etanercept is a soluble anti-tumor necrosis factor alpha (TNF-alpha) agent licensed for the treatment of active poly-articular juvenile idiopathic arthritis (JIA) in children aged 4 to 17 years who have failed to respond to methotrexate alone, or who have been intolerant of methotrexate. The safety and efficacy of etanercept in this patient group has been established by one randomized controlled trial and several longitudinal studies. This, together with the fact that until recently etanercept was the only anti-TNF licensed in JIA, has made it the most common first choice biologic for many clinicians. However, there are still many unanswered questions about etanercept, including its efficacy and safety in different subtypes of JIA, in children under 4 years of age and in those with uveitis. There are still concerns about the long term safety of TNF antagonists in the pediatric age group and unanswered questions about increased risks of malignancy and infection. Although adult studies are useful to improve understanding of these risks, they are not a substitute for good quality pediatric research and follow-up studies. Adult trials often include greater numbers of patients. However, they evaluate a different population and drug behavior may vary in children due to differences in metabolism, growth and impact on a developing immune system. In addition, rheumatoid arthritis is a different disease than JIA. Clinicians need to carefully weigh up the risk benefit ratio of anti-TNF use in children with JIA and push for robust clinical trials to address the questions that remain unanswered. This article summarizes the evidence available for use of etanercept in children with JIA and highlights aspects of treatment in need of further research. | |
21141332 | Peripheral ulcerative keratitis triggered by bacterial conjunctivitis. | 2010 Jan | BACKGROUND: Periphpral ulcerative keratitis (PUK) is a disorder consisting of a crescent-shaped destructive inflammation of the perilimbal corneal stroma. CASE: We present a case of PUK following acute bacterial conjunctivitis in a 60-year-old lady with a history of on-and-off joint pain for two years. After admission to the hospital, she underwent conjunctival resection and was given topical and oral steroids. She was prescribed hydroxychloroquine after confirming the diagnosis of rheumatoid arthritis with a positive RA factor. CONCLUSION: This report highlights the role of infection as a triggeringagent in the induction of PUK in an otherwise quiescent cornea. | |
20158096 | [Pleiotropic effects of PPARgamma agonists on bone remodeling]. | 2010 Feb | Peroxisome proliferator-activated receptor-gamma (PPARgamma) regulates both glucose and bone mass. PPARgamma activation has been shown to affect bone through an increased in bone marrow adiposity and decreased in osteoblastogenesis, resulting in reduced bone formation. In fact, clinical studies have reported that PPARgamma agonists may cause increased risk of bone fractures and decreased bone mineral density. On the other hand, PPARgamma agonists may have protective effect on inflammatory bone resorption through inhibition of RANKL- or TNFalpha-induced osteoclastogenesis. In this report, we review recent studies showing pleiotropic effects of PPARgamma agonists on bone formation and inflammatory bone resorption observed at joints in rheumatoid arthritis. | |
19449080 | Is there a role for NFAT inhibitors in the prevention of bone destruction? | 2009 Sep | Pathologic conditions resulting from excessive bone destruction include osteoporosis, rheumatoid arthritis, metastases, periprosthetic osteolysis, cherubism, and others. A scarcity of molecular targets in bone has thwarted the development of drugs to combat these conditions. Nuclear factor of activated T-cells (NFAT) is a master regulator of osteoclastogenesis and is induced by RANKL. The immunosuppressive drugs, Cyclosporin A and Tacrolimus, inhibit osteoclast formation by targeting the NFAT/calcineurin pathway. These NFAT inhibitors should be considered in the treatment of osteoclastic hyper-resorptive syndromes. | |
19403095 | Pain and the brain: chronic widespread pain. | 2009 Apr | Chronic widespread pain is associated with several medical and psychiatric disorders including, but not limited to, chronic fatigue syndrome, fibromyalgia, mood disorders, hepatitis, endocrine disorders such as hypothyroidism, and rheumatologic disorders such as rheumatoid arthritis. Careful and comprehensive differential diagnosis must be performed to ensure a correct diagnosis before an appropriate treatment can be selected. Fibromyalgia, in particular, is challenging to diagnose and treat because it shares many characteristics with other disorders and is commonly concurrent with major mood disorders. A comprehensive disease management strategy including patient education, pharmacotherapy, cognitive-behavioral therapy, and aerobic and other forms of exercise can be beneficial for many patients with fibromyalgia. | |
20062693 | An acutely erythematous, oedematous penis and antecubital fossae rash in a patient taking | 2009 Nov 30 | INTRODUCTION: Acute erythema and oedema of the genitalia is an alarming complaint for any patient. Diagnosis can be complicated by atypical presentation and the use of concurrent immuno-modulatory drugs. CASE PRESENTATION: We present a case report of a man on anti-TNF therapy for rheumatoid arthritis presenting with an acutely red, swollen, non-tender penis and scrotum presumed to be infective. The discovery of erythematous plaques in both antecubital fossae alerted the clinicians to consider alternative dermatological diagnoses. CONCLUSION: The accepted adjuncts to confirming or excluding infectious aetiology were complicated by the use of immuno-modulatory medication in this case. This patient's unusual presentation may have been associated with and was complicated by the use of etanercept. The case illustrates the need to consider other diagnoses and obtain appropriate advice when the clinical course is not progressing as anticipated. | |
19200021 | New potential targets to modulate neutrophil function in inflammation. | 2009 Feb | The importance of neutrophils in human disease such as rheumatoid arthritis, asthma, adult respiratory distress syndrome, and COPD has prompted the search for drugs capable to slow down neutrophil-dependent inflammation, without interference with innate immune responses. In this review, we summarize new potential drugs targets against neutrophils mediated inflammatory responses. | |
18843521 | Mycobacterium chelonae infection following silicone arthroplasty of the metacarpophalangea | 2009 Jun | We present a case of infection caused by an uncommon pathogen, Mycobacterium chelonae, in a patient that underwent Swanson silicone arthroplasty of the metacarpophalangeal joints for rheumatoid arthritis. This is the first report of an infection caused by nontuberculous Mycobacteria in flexible silicone implants in the hand. The patient was successfully treated with implant removal, debridement, and antimicrobials tailored to the results of in vitro susceptibility testing. | |
19849821 | Outcome measures in inflammatory rheumatic diseases. | 2009 | Inflammatory rheumatic diseases are generally multifaceted disorders and, therefore, measurement of multiple outcomes is relevant to most of these diseases. Developments in outcome measures in the rheumatic diseases are promoted by the development of successful treatments. Outcome measurement will increasingly deal with measurement of low levels of disease activity and avoidance of disease consequences. It is an advantage for patient management and knowledge transfer if the same outcomes are used in practice and in trials. Continuous measures of change are generally the most powerful and, therefore, are preferred as primary outcomes in trials. For daily clinical practice, outcome measures should reflect the patients' state and have to be easily derivable. The objective of this review is to describe recent developments in outcome measures for inflammatory rheumatic diseases for trials and clinical practice, with an emphasis on rheumatoid arthritis. | |
21358257 | Rice body mass formation mimicking a neoplastic disease around the trochanteric bursae of | 2010 | Multiple rice body formation is an uncommon inflammatory process. Sometimes it leads to a big mass in unusual locations. Although sometimes associated with bursitis and systemic diseases, such as rheumatoid arthritis, the pathophysiology of this rare entity is still obscure. We present a 29-year-old woman with multiple rice body mass formation in the trochanteric bursa of the left hip. She was operated, and had no recurrence at 18 months after the surgery. |