Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 18165132 | Long-term outcome of total knee replacement in patients with rheumatoid arthritis. | 2008 Mar | OBJECTIVES: We analysed the long-term clinical and radiological results of 68 consecutive total knee replacements in 50 patients with rheumatoid arthritis. METHODS: At a mean follow-up of 11.2+/-1.2 years (range, 9.7-13.7) all revisions were included. Thirty-seven knees in 28 patients still alive were followed retrospectively clinically and radiologically, all other patients who died without revision were censored at time of the last clinical follow-up and no patient was lost to follow-up. Revision was necessary in 13 knees (19%, one revised twice), including an overall deep infection rate of 1.47%. RESULTS: The survival rate was 81.6+/-0.05% at 12 years with any revision or removal of the prosthesis as an end point. There was no significant difference in survival between cemented, uncemented or hybrid fixation (log rank, 0.2544). The average Knee Society Scores were 77.2 points clinical (range, 40-95 points) and 75.3 points functional (range, 30-100 points), respectively, at final follow-up. The body mass index (BMI) was 25.9 at surgery and 25.3 at follow-up (n.s.). There was no correlation between BMI, age, side, gender and revision frequency. No arthroplasty was at risk for removal or revision at follow-up. CONCLUSIONS: The study shows good 10-12-year clinical and radiological results for the PCA knee replacement in patients with rheumatoid arthritis without preference for the method of fixation or patient weight. | |
| 16447221 | Activation of p38 MAPK is a key step in tumor necrosis factor-mediated inflammatory bone d | 2006 Feb | OBJECTIVE: To investigate whether activation of p38 MAPK is a crucial signaling factor in inflammatory bone destruction mediated by tumor necrosis factor (TNF). Mice overexpressing TNF were treated with 2 different inhibitors of p38 MAPK, and the effect of this treatment on joint inflammation and structural damage was assessed. METHODS: Human TNF-transgenic mice received systemic treatment with 2 different p38 MAPK inhibitors (RO4399247 and AVE8677). Treatment was started at the time of symptom onset and lasted for 6 weeks. Mice were assessed for clinical signs of arthritis, bone erosion, and cartilage damage. In addition, the effect of these inhibitors on osteoclast generation in vitro and in vivo was assessed. RESULTS: Both p38 MAPK inhibitors significantly reduced clinical signs of TNF-mediated arthritis. This was attributable to reducing synovial inflammation by 50% without affecting the cellular composition of the infiltrate. Synovial expression of interleukin-1 and RANKL was reduced upon p38 MAPK blockade, and activation of the molecular target MAPK-activated protein kinase 2 (MAPKAP-2) was also inhibited. Proteoglycan loss of articular cartilage was reduced by 50%, although p38 MAPK inhibition did not change matrix molecule synthesis by cultivated chondrocytes. Importantly, bone loss was almost completely prevented by p38 MAPK inhibition. The numbers of synovial osteoclasts and precursors were dramatically reduced, and both p38 MAPK inhibitors also inhibited in vitro osteoclastogenesis at micromolar concentrations and blocked activation of MAPKAP-2 as well as differentiation markers in cultured osteoclast precursors. CONCLUSION: These results suggest the major importance of p38 MAPK for TNF-mediated inflammatory bone destruction in arthritis and suggest that inhibition of p38 MAPK might be an important tool for reducing structural damage in rheumatoid arthritis. | |
| 19006761 | Effectiveness of a MP-blocking splint and therapy in rheumatoid arthritis: a descriptive p | 2008 Oct | The purpose was to evaluate the effect of a metacarpal phalangeal joint blocking splint combined with exercises, aimed at regaining strength, manipulative skills, and a normal pattern of movement of the hands in patients with rheumatoid arthritis (RA). All patients were measured three times: before the start of the therapy, after finishing the therapy, and at three months follow-up. Outcome measures were grip strength, pinch strength (Jamar dynamometer and pinchmeter), active range of motion (goniometer), dexterity (Sequential Occupational Dexterity Assessment [SODA]), and experienced functioning in daily life (Michigan Hand Outcome Questionnaire and Disability of Arm, Shoulder, and Hand questionnaire). The hands treated improved significantly on both total SODA score and on the pain score of the SODA. This means that the dexterity improved over time. No significant changes were found on the other outcome measures. This study indicates that intervention on the function of the hands in patients with RA who present an intrinsic-plus posture and movement pattern, improve significantly on dexterity and pain, measured by the SODA. | |
| 17424701 | [Rheumatoid arthritis: current status of therapy]. | 2007 Jan | Rheumatoid Arthritis (RA) is a frequent chronic inflammatory disease characterized by distal, bilateral and symmetrical lesions, leading to joint distortions and articular destructions. RA can also cause severe extra-articular manifestations associated with a poor prognosis. Recent advances in the field of immunopathology of RA have oriented treatment targeting the pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF alpha), interleukin (IL) and IL6. These biotherapies are considered as an important therapeutic progress in the treatment of RA acting at the level of cellular processes responsible for rheumatoid disease. These new therapies are active not only in controlling the disease inflammatory processes but also to stop the radiological course of RA. These new therapies are however efficient as long as prescribed, their interruption being rapidly followed by a flare-up of RA. Multiple adverse events attributed to anti-TNF-alpha have been described especially severe opportunistic infections and tuberculosis. B cells playing a critical role in sustaining the chronic inflammatory process in RA, targeted depleting B cells therapies have been developed in refractory forms of RA giving promising results. However, before any biotherapy prescription especially of anti-TNF-alpha, an initial screening should be achieved to exclude patients with history of untreated tuberculosis, solid cancers, malignant hemopathies or demyelinating disorders. It is also essential to assure a strict follow-up in patients under biotherapy to detect adverse events that can be sometimes severe. Thus, the ratio benefit/risk must be evaluated before any biotherapy prescription. | |
| 16920501 | Dendritic cells: vehicles for tolerance induction and prevention of autoimmune diseases. | 2006 | Adaptive immune responses are orchestrated by specialized professional antigen-presenting cells (APCs), the dendritic cells (DCs), which play crucial roles as initiators and modulators of adaptive immune responses. A main feature of DCs is their phenotypic and functional plasticity. In the absence of any inflammation or pathogenic elements, most DCs in peripheral tissues and lymphoid organs have a resting, immature phenotype characterized by high endocytic capacity and low surface expression of MHC- and costimulatory molecules. However, upon interaction with microbial ligands, pro-inflammatory cytokines or CD40Ligand, DCs rapidly acquire an activated phenotype. These mature DCs have a very efficient T cell-priming ability as a consequence of upregulation of MHC- and costimulatory molecules on their cell surface. For this reason, DC-based vaccines have been used successfully to combat infections and malignancies. Nonetheless, evidence is accumulating that, especially immature, or semi-matured, DCs also have a potent ability to tolerize T cells or prevent undesired immune reactions. Therefore, current and prospective strategies to promote the inherent tolerogenic potential of DCs are a rational approach for the therapy of autoimmune diseases such as rheumatoid arthritis (RA). This review summarizes some aspects of the intriguing ability of DCs to steer the outcome of immunity and their potency to modulate the outcome of various pathological conditions. | |
| 17968879 | Rheumatoid arthritis fibroblast-like synoviocytes express BCMA and are stimulated by APRIL | 2007 Nov | OBJECTIVE: Fibroblast-like synoviocytes (FLS) are among the principal effector cells in the pathogenesis of rheumatoid arthritis (RA). This study was undertaken to examine the variety of stimulating effects of APRIL and its specific effect on FLS in the affected RA synovium. METHODS: Synovium and serum samples were obtained from patients with RA, patients with osteoarthritis (OA), and healthy subjects. Soluble APRIL proteins were assayed by enzyme-linked immunosorbent assay. The relative gene expression of APRIL, BCMA, interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), IL-1beta, and RANKL was assessed in RA and OA FLS by polymerase chain reaction. Effects of APRIL on the production of proinflammatory cytokines and RANKL in RA FLS were investigated by flow cytometry and with the use of a BCMA-Fc fusion protein. RESULTS: A significantly higher level of soluble APRIL was detected in RA serum compared with normal serum. Among the 3 receptors of APRIL tested, RA FLS expressed only BCMA, whereas OA FLS expressed none of the receptors. APRIL stimulated RA FLS, but not OA FLS, to produce IL-6, TNFalpha, IL-1beta, and APRIL itself. In addition, APRIL increased RA FLS expression of RANKL and also enhanced progression of the cell cycle of RA FLS. Neutralization of APRIL by the BCMA-Fc fusion protein attenuated all of these stimulating effects of APRIL on RA FLS. CONCLUSION: RA FLS are stimulated by APRIL and express the APRIL receptor BCMA. These results provide evidence that APRIL is one of the main regulators in the pathogenesis of RA. | |
| 18521455 | Anti-xanthine oxidase antibodies in sera and synovial fluid of patients with rheumatoid ar | 2008 Jun | OBJECTIVE: To study anti-bovine milk xanthine oxidoreductase XOR antibody levels in synovial fluid as well as in serum of patients suffering from rheumatoid affections to assess a possible correlation between antibody titres and severity of disease. METHODS: Sera and synovial fluids were collected from volunteer donors at Setif University Hospital, Setif, Algeria from 2001--2007 with the consent of patients. Human IgG and IgM levels of free and bound anti-bovine milk XOR antibodies were determined using bovine XOR as antigen, with enzyme-linked immunosorbent assay ELISA. RESULTS: Serum IgG anti-bovine milk XOR titres in 30 healthy normal subjects 2.74+/-2.31 microgram/mL are in agreement with that reported in the literature. Immunoglobulin G and IgM anti-bovine milk XOR antibody titres were found to be significantly higher in serum from patients with rheumatoid arthritis RA, and latex positives subjects. Synovial IgM antibody titres to bovine XOR were found to be significantly higher in rheumatoid arthritis patients compared to patients with other joint inflammations. CONCLUSION: In rheumatoid arthritis patients, high concentrations of antibodies against XOR were noticed. These antibodies may play a major role in RA by inhibiting both xanthine and NADH oxidase activities of XOR. They may also play a key role in eliminating XOR from serum and synovial fluid positive role but unfortunately, immune complex formation could also activate complement and participate in self maintenance of inflammation. | |
| 16338211 | The CORRONA database. | 2006 Jan | BACKGROUND: Large, long-term databases are needed in order to provide information on the safety and efficacy of new agents used in the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA). These databases can provide data which is well beyond what is available from industry-sponsored investigations. METHODS: The structure, governance, content, context and developmental plan of the CORRONA database are described. RESULTS: The CORRONA database has grown from start up in 2002 to the largest independent database in North America which collects data from both rheumatologists and patients at the time of a clinical encounter. Data are collected as often as every 3 months in RA and every 6 months in PsA. As of the time of this writing, the CORRONA database consists of approximately 9000 patients with RA and 1000 with PsA. Data can be used to elucidate toxicities found in frequencies which would be considerably less common than can be uncovered in industry-sponsored investigations. In addition, actual prescribing patterns and responses in clinical practice can be investigated and described. CONCLUSION: After 3 years of data collection, the CORRONA database is now appropriately able to make significant contributions to our understanding of the safety, efficacy of drugs, as well as demographic, and socioeconomic profiles of patients with RA and PsA. It has evolved from a nascent database to a mature one poised to make significant contributions. | |
| 17080202 | Cortistatin as a potential multistep therapeutic agent for inflammatory disorders. | 2006 Sep | The induction of immune tolerance is critical for the prevention of autoimmunity and the maintenance of immune homeostasis. The identification of factors involved in the maintenance or restoration of such tolerance has become the focus of new therapies for inflammatory and autoimmune diseases. Cortistatin, a recently discovered cyclic neuropeptide related to somatostatin, has emerged as a potential endogenous antiinflammatory factor based on its production by, as well as its binding to, immune cells. Thus, cortistatin has been found to downregulate the inflammatory response mediated by activated macrophages. The present work reviews various recent studies involving different experimental models of sepsis, rheumatoid arthritis and inflammatory bowel disease, demonstrating that cortistatin treatment offers great benefits at both the clinical and pathological levels. These include the downregulation of both inflammatory and Th1-mediated autoimmune disease components and the emergence of regulatory T cells (Treg) that suppress autoreactive T cells, both of which contribute to the restoration of immune tolerance. While many questions need to be resolved, cortistatin appears to be an exciting and promising candidate for the treatment of several chronic inflammatory diseases and autoimmune disorders. | |
| 18594491 | Control of autoimmune diseases by the vitamin D endocrine system. | 2008 Aug | 1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], the biologically active form of vitamin D(3), is a secosteroid hormone essential for bone and mineral homeostasis. It regulates the growth and differentiation of multiple cell types, and displays immunoregulatory and anti-inflammatory properties. Cells involved in innate and adaptive immune responses--including macrophages, dendritic cells, T cells and B cells--express the vitamin D receptor (VDR), and can both produce and respond to 1,25(OH)(2)D(3). The net effect of the vitamin D system on the immune response is an enhancement of innate immunity coupled with multifaceted regulation of adaptive immunity. Epidemiological evidence indicates a significant association between vitamin D deficiency and an increased incidence of several autoimmune diseases, and clarification of the physiological role of endogenous VDR agonists in the regulation of autoimmune responses will guide the development of pharmacological VDR agonists for use in the clinic. The antiproliferative, prodifferentiative, antibacterial, immunomodulatory and anti-inflammatory properties of synthetic VDR agonists could be exploited to treat a variety of autoimmune diseases, from rheumatoid arthritis to systemic lupus erythematosus, and possibly also multiple sclerosis, type 1 diabetes, inflammatory bowel diseases, and autoimmune prostatitis. | |
| 18328145 | Nottingham health profile questionnaire incorporates important aspects of the patient pers | 2008 Jan | OBJECTIVE: There is a consensus on the need for a more thorough assessment of outcome of RA from the perspective of those who experience the disease. Our objective was to assess the health- related quality of life (HR-QOL) of RA patients by the Nottingham Health Profile (NHP), the measurement of subjective experienced distress. METHODS: One hundred and nineteen consecutive out-patients were cross-sectionally assessed. HR-QOL was evaluated by using the first section of the NHP, a generic quality of life instrument, that assess subjective distress on six dimensions: mobility, pain, energy, sleep, emotional reaction and social isolation. Functional capacity was measured by the Health Assessment Questionnaire (HAQ). RESULTS: The NHP scores for mobility, pain, energy and sleep showed a linear association (p<0.001 for each) with HAQ disability level. In addition to pain, patients with mild disability (HAQ 0-1) may suffer from remarkable fatigue (loss of energy) and problems in sleep. Even at the HAQ level 0, there was some perceived distress in almost all of the NHP dimensions. CONCLUSIONS: Poor HAQ levels were associated with patient perceived distress in dimensions which are getting minor attention in clinics, i.e., energy and sleep. It is to be noted that RA patients who reported no disability or its lowest levels measured by HAQ perceived notable distress in many NHP dimensions. Our results suggest that NHP is a potential candidate for a HR-QOL questionnaire which should considered to be used in routine clinical assessment of RA patients. | |
| 16393443 | Real-world utilization of DMARDs and biologics in rheumatoid arthritis: the RADIUS (Rheuma | 2006 Jan | OBJECTIVE: Rheumatoid Arthritis (RA) Disease-Modifying Anti-Rheumatic Drug (DMARD) Intervention and Utilization Study (RADIUS) is a unique, real-world, prospective, 5-year, observational study of over 10 000 patients with RA. RADIUS provides a snapshot of use patterns, effectiveness, and safety of DMARDs, biologics, and combination therapies used to manage RA in clinical practice. RESEARCH DESIGN AND METHODS: Patients with RA requiring a new DMARD or biologic (addition or switch) were eligible for the RADIUS study. Two separate patient cohorts were enrolled; RADIUS 1 patients initiated any new therapy at entry, and RADIUS 2 patients initiated etanercept at entry. Patient demographics and disease activity measures were collected at study entry, and baseline characteristics were summarized for various subgroups. Effectiveness, safety, and patterns of use will be tracked for therapies utilized during the 5-year study. RESULTS: RADIUS 1 enrolled 4959 patients, and RADIUS 2 enrolled 5102 patients, mostly at community private practices (88%). In RADIUS 1, most patients initiated methotrexate (MTX) monotherapy, followed by MTX in combination with a biologic (e.g. infliximab plus MTX) or other DMARD. In RADIUS 2, most patients initiated etanercept in combination with MTX, followed by etanercept monotherapy. When a new therapy was required, physicians tended to add another therapy versus switching therapies. Patients initiating a biologic had a longer duration of RA and more severe disease compared with patients initiating non-biologic therapy. CONCLUSIONS: These real-world data provide evidence of the prescribing practices of rheumatologists in 2001-2003. Future analyses will allow evidence-based comparisons of the long-term safety and effectiveness of DMARDs, biologics, and combination therapies to assist physicians in clinical decision-making. | |
| 17313619 | Abatacept in the treatment of rheumatoid arthritis. | 2007 Mar | Over the past decade, biological immunotherapy has revolutionised the treatment of rheumatoid arthritis (RA). The most widely used of these therapies targets tumour necrosis factor-alpha (TNF-alpha). Approximately 20% of patients fail to respond to TNF-alpha antagonism, however, and a significant number of additional patients become refractory to anti-TNF-alpha therapy over time. Thus investigators have sought to target other pathogenic elements of RA using novel biological therapies. Abatacept is the first immunotherapy directed against the process of T-cell costimulation. Abatacept has shown clinical effectiveness in RA by improving disease activity, quality of life measures and radiographic progression of disease. In this article, we review the immunology of T-cell activation and costimulation, define the role of abatacept in this process, and discuss the clinical trials that led to the approval of abatacept as the latest biological therapy in RA in the USA and Canada. We also address the role of abatacept in the greater context of biological therapy for RA. | |
| 16735454 | Bone marrow B-lineage cells in patients with rheumatoid arthritis following rituximab ther | 2007 Jan | OBJECTIVE: To assess the presence and phenotype of B-lineage cells in the bone marrow (BM) of rheumatoid arthritis (RA) patients after rituximab therapy. METHODS: Six patients were studied. BM aspirates were collected 3 months after the treatment and analysed using the four-colour flow cytometry. RESULTS: CD19+ (B-lineage) cells in BM samples varied from 0.1 to 3.25% in the lymphoid gate. CD34+ cells varied from 1.23 to 4.86%. The proportion of CD34+ cells committed to the B-lineage varied between 0 and 42.19%. Pro-B-cells were undetectable in one case. The majority of B-cell precursors were pro-B-cells in Patients 5 and 6 (50 and 62% of CD19+ cells, respectively), pre-B-cells in Patients 3 and 4 (64 and 70%) and immature B-cells in Patient 1 (44%). Detectable CD20 expression on CD19+ cells was either low or absent. Plasma cells varied from 0.01 to 0.36% of the total nucleated cells. There was a trend towards longer duration of clinical response in patients with evidence of more complete depletion in BM. CONCLUSION: In this small cohort of RA patients treated with rituximab, differences in proportion and phenotype of CD19+ BM cells were detected. These differences suggest variation in the degree of depletion achieved and correlate with time to relapse. Although pro-B-cells are not targeted directly by rituximab as they do not express CD20, the levels were unexpectedly low. | |
| 18677493 | Nonunion of distal radius fracture and distal radioulnar joint injury: a modified Sauvé-K | 2008 Dec | The Sauvé-Kapandji (SK) procedure is indicated in distal radius nonunion or malunion and distal radioulnar joint (DRUJ) instability. It can also be used to treat the rheumatoid wrist with severe degenerative changes in the DRUJ. The main objective is to allow a pain-free range of movement. We present a patient with rheumatoid arthritis and distal radius nonunion who, after three operations, was treated with the SK procedure. The clinical and radiological results were excellent. A 53-year-old woman diagnosed with rheumatoid arthritis fell on her forearm at home 2 years ago. Examination at an outpatient clinic revealed a distal radius fracture classified as type V according to the Frykman classification. She had been operated three times with open reduction internal fixation using a plate, screws, and bone allograft. She came to our institution with a distal radius nonunion, positive post-traumatic ulnar variance, and ulnar nerve paresis. The range of movements was 20 degrees -10 degrees flexion-extension and 40 degrees -30 degrees pronation-supination, and she needed daily fentanyl. We performed a modified SK procedure with an autologous iliac crest bone graft and ulnar bone graft from the osteotomy area (cubitus proradius), bone morphogenetic protein, and a low profile distal radius plate. After 1 year of follow-up, the distal radius fracture has healed and the wrist is pain-free with a complete range of movement in flexion-extension and pronation-supination. The main indication for the SK procedure is post-traumatic positive ulnar variance and associated ulnocarpal impaction. The cubitus proradius bone graft transposition is an interesting technical note that makes this case a challenge for skilled orthopedic hand surgeons. | |
| 17268510 | The arthritis severity quantitative trait locus Cia7 regulates neutrophil migration into i | 2007 Mar | Neutrophils are required for the development of arthritis in rodents, and are the predominant cell in the synovial fluid of active rheumatoid arthritis. We hypothesized that neutrophil migration into the inflammed joint is genetically regulated. In addition, this genetic regulation would be accounted for by one of the arthritis loci that we have previously identified in an intercross between arthritis-susceptible DA and arthritis-resistant ACI rats studied for collagen-induced arthritis. We used the synovial-like air pouch model injected with carrageenan, and tested DA, ACI, and four congenic strains. ACI exudates had a significantly lower number of neutrophils compared with DA. Transfer of DA alleles at Cia7 into the ACI background, as in ACI.DA(Cia7) congenics, was enough to increase exudate neutrophil numbers to levels identical to DA, and this locus accounted for the difference between parental strains. None of the other congenic intervals explained the differences in exudate neutrophil counts. In conclusion, we have identified a novel function for Cia7, and determined that it regulates neutrophil migration into a synovial-like inflammatory site. Our data revealed no intrinsic defect in neutrophil responses to chemotactic agents, and suggest that Cia7 regulates an as yet unidentified factor central to neutrophil recruitment into inflammed tissues. | |
| 17483636 | [Extensor indicis proprius transfers for extensor pollicis longus ruptures secondary to rh | 2007 | OBJECTIVES: We evaluated the results of extensor indicis proprius (EIP) to extensor pollicis longus (EPL) transfers for EPL ruptures secondary to rheumatoid arthritis. METHODS: Twenty-four patients (7 males, 17 females; mean age 41 years; range 22 to 72 years) with rheumatoid arthritis underwent EIP to EPL transfer for 25 ruptures. The mean duration from rupture to surgery was 4.3 months (range 1.5 to 11 months). Functional assessment of the fingers was made using a specific EIP-EPL evaluation method developed by Lemmen et al. Pinch and grip strengths were measured. Range of motion of the metacarpophalangeal and interphalangeal joints of the thumb was compared with the normal side. Patient satisfaction was evaluated by a visual analog scale. The mean follow-up period was 6.2 years (range 4.7 to 7.9 years). RESULTS: Functional results were perfect in 14 fingers (56%), good in six fingers (24%), moderate in four fingers (16%), and poor in one finger (4%). The pinch and grip strengths were 86% and 92% of the uninvolved hand, respectively. The mean visual analog scale score was 74 (range 24 to 99). Compared to the uninvolved side, the range of motion of the thumb and index finger decreased by 23 degrees and 7 degrees , respectively, with a 9% loss of interphalangeal motion and a 17% loss of metacarpophalangeal motion in thumb extension. Independent extension of the index finger was possible in 21 hands. CONCLUSION: The results of EIP to EPL transfers are successful in ruptures secondary to rheumatoid arthritis. | |
| 18037625 | Anti-tumour necrosis factor treatment in patients with refractory systemic vasculitis asso | 2008 Jun | OBJECTIVE: To assess anti-tumour necrosis factor (anti-TNF) agents in patients with refractory systemic rheumatoid vasculitis (SRV). METHODS: 1200 rheumatologists and internists were asked to provide medical files for patients with anti-TNF agents given as a second-line treatment for active SRV refractory to cyclophosphamide and glucocorticoids. RESULTS: We identified nine cases in which anti-TNF drugs were given for active SRV, despite previous treatment with a mean cumulative dose of 8.4 g of cyclophosphamide in association with high-dose glucocorticoids. The mean prednisone dose before anti-TNF therapy was 29.6 mg/day. After 6 months, six patients were in remission (complete in five, partial in one). The treatment failed in one patient and two patients stopped taking the anti-TNF treatment due to side-effects. Mean prednisone dose was reduced to 11.2 mg/day. Severe infection occurred in three patients. Relapses were observed in two patients. Remission was re-established by reintroducing anti-TNF therapy in one case and increasing the dose in the other. CONCLUSIONS: This study provides evidence of efficacy of anti-TNF therapy in adjunct to glucocorticoids for treating active refractory SRV. Remission was achieved in two-thirds of patients, with a significant decrease in prednisone dose, although there was a high rate of infection in these severely ill patients. | |
| 18438844 | Expression of microRNA-146 in rheumatoid arthritis synovial tissue. | 2008 May | OBJECTIVE: Several microRNA, which are approximately 22-nucleotide noncoding RNAs, exhibit tissue-specific or developmental stage-specific expression patterns and are associated with human diseases. The objective of this study was to identify the expression pattern of microRNA-146 (miR-146) in synovial tissue from patients with rheumatoid arthritis (RA). METHODS: The expression of miR-146 in synovial tissue from 5 patients with RA, 5 patients with osteoarthritis (OA), and 1 normal subject was analyzed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and by in situ hybridization and immunohistochemistry of tissue sections. Induction of miR-146 following stimulation with tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta) of cultures of human rheumatoid arthritis synovial fibroblasts (RASFs) was examined by quantitative PCR and RT-PCR. RESULTS: Mature miR-146a and primary miR-146a/b were highly expressed in RA synovial tissue, which also expressed TNFalpha, but the 2 microRNA were less highly expressed in OA and normal synovial tissue. In situ hybridization showed primary miR-146a expression in cells of the superficial and sublining layers in synovial tissue from RA patients. Cells positive for miR-146a were primarily CD68+ macrophages, but included several CD3+ T cell subsets and CD79a+ B cells. Expression of miR-146a/b was markedly up-regulated in RASFs after stimulation with TNFalpha and IL-1beta. CONCLUSION: This study shows that miR-146 is expressed in RA synovial tissue and that its expression is induced by stimulation with TNFalpha and IL-1beta. Further studies are required to elucidate the function of miR-146 in these tissues. | |
| 17881662 | Why is gout so poorly managed? | 2007 Oct | See linked article, p1309 |