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ID PMID Title PublicationDate abstract
19092421 Peripheral ulcerative keratitis after trabeculectomy in a patient with rheumatoid arthriti 2009 Jan PURPOSE: To report the unusual occurrence of peripheral ulcerative keratitis, 10 days after trabeculectomy in a 35-year-old patient with rheumatoid arthritis (RA). METHODS: Observational case report. RESULTS: A 35-year-old patient with RA and secondary Sjögren disease underwent an uneventful fornix-based trabeculectomy. Ten days after surgery, slit-lamp examination revealed a peripheral corneal ulcer extending from 5- to 7-o'clock positions with a surrounding inflammatory infiltrate and adjacent conjunctival injection. The ulcer was treated with systemic and topical steroids, antibiotic eyedrops, artificial tears, and a bandage soft contact lens. Since then, corneal re-epithelialization started and the patient's symptoms subsided. The ulcer improved steadily within 2 months while the patient used a soft contact lens. The ulcer did not reoccur in the 18 months follow-up while the patient remained under systemic treatment. CONCLUSION: This report highlights the importance of careful examination and close postoperative follow-up in patients with RA undergoing any intraocular surgery, to diagnose a possible development of peripheral ulcerative keratitis. Although the incidence is rare, prompt diagnosis of the peripheral ulceration is essential because if untreated it may seriously affect patient's vision.
21098574 CXCL13: a novel biomarker of B-cell return following rituximab treatment and synovitis in 2011 Mar OBJECTIVES: The B-cell chemokine, CXCL13, is a proposed serum biomarker of synovitis in RA. Its behaviour in the context of B-cell depletion therapy and reconstitution was studied during treatment of RA with rituximab. METHODS: Serum samples from 20 RA patients were analysed for CXCL13, RF-IgM and anti-CCP by ELISA before and 2 and 6 months following rituximab treatment. B cells were monitored by flow cytometry. Gene expression in blood and synovial biopsies was determined by qPCR. RESULTS: Patients with detectable B cells at 6 months had significantly higher levels of CXCL13 and RF-IgM and slightly higher levels of anti-CCP throughout the study, including at baseline, compared with patients with undetectable B cells at 6 months. Conversely, 10 of 12 patients with high baseline CXCL13 had detectable circulating B cells at 6 months, whereas no B cells could be detected at 6 months in patients with low baseline CXCL13. Synovial CXCL13 expression at baseline correlated significantly with serum CXCL13 levels, and the synovium of patients with high serum CXCL13 expressed elevated levels of IL-1β, IL-8, MMP1 and MMP3. In addition, synovial CXCL13 expression correlated significantly with several synovial inflammatory markers. CONCLUSIONS: Serum CXCL13 is predictive of the rate of B-cell repopulation following a course of rituximab in RA. Serum CXCL13 correlates with synovial CXCL13 measured at a single joint, suggesting synovitis as an important source of circulating CXCL13. Within the synovium, CXCL13 expression is highly correlated with markers of synovitis. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00147966.
19531761 Severe disease activity and complications of immunosuppressive therapy: a challenge for ac 2009 Aug Acute rehabilitation refers to the multidisciplinary rehabilitative treatment of patients in continuing need of integrated acute and rehabilitative longterm care. As a result of the advances in acute rheumatology and improved emergency services, an increasing number of patients survive episodes of severe disease and complications of immunosuppressive therapy. These patients require not only treatment of their acute medical problems but also specialized multidisciplinary acute rehabilitation starting as early as possible during their hospital stay. We describe 4 typical cases from the major fields of rheumatology. (1) Acute rehabilitation of a 63-year-old woman with rheumatoid arthritis after replacement of both preexisting knee endoprostheses in one session and removal of the left hip endoprosthesis due to infection and sepsis. (2) Rehabilitation of a 29-year-old man with a 7-year history of ankylosing spondylitis who lived in an adjustable easy chair for 2 years due to severe pain prior to admission. (3) A 61-year-old woman with active refractory Wegener's granulomatosis who developed respiratory insufficiency due to aspergillus and pseudomonas pneumonia. (4) The acute rehabilitation of a 21-year-old woman with systemic lupus erythematosus and a history of 14 laparotomies due to severe acute pancreatitis and multiple gut perforations. Acute rehabilitation was complicated by a large defect of the abdominal wall and significant critical illness polyneuropathy. Our report points out differences between acute, postacute, and longterm rehabilitation, describes the mobilization of patients in acute rheumatology units, and defines specific problems encountered in acute hospital-based rehabilitation of rheumatological patients.
19189248 [Wrist joint arthroplasty: results after 41 prostheses]. 2009 Jun PURPOSE: The advantage of wrist arthroplasty remains controversial, primarily due to the high complication rate. For this reason it seems sensible to monitor the results of different types of prostheses even with small numbers of cases. We were particularly interested to see if wrist joint arthroplasty is a useful alternative for patients with rheumatoid arthritis, and which of the types we used shows the best results. PATIENTS AND METHODS: In our hospital, 41 wrist joint prostheses (15 Meuli, 16 BIAX and 10 Universal 2) were implanted in 36 patients from 1992 until 2005 (follow-up 1 to 14 years, mean 5.3 years). 33 patients had rheumatic destruction of the wrist, two had osteoarthritis following fracture of the scaphoid, and one pseudarthrosis after failed arthroplasty and arthrodesis for Kienböck's disease. Mean age was 54 years, ranging from 34 to 73 years. 14 patients had had surgery on this wrist before. The patients were sent a questionnaire including the DASH score, and a clinical evaluation and X-rays were performed. RESULTS: 33 patients with 38 wrist arthroplasties answered the questionnaire, 34 wrist joint prosthesis of 29 patients could be evaluated. DISCUSSION: 6 prostheses had to be removed because of complications (3 arthrodeses were performed after removal, 3 prostheses were exchanged). There were 4 dislocations (3 times with the Meuli type, once with the BIAX type). There was one case of CRPS type I. But subjectively, in answering our questionnaire, 31 of 38 patients claimed to be very satisfied or satisfied with the result of the operation, only 6 were less satisfied or not satisfied at all. An improvement of pain was found by all but one patient. An increase in strength or range of movement was found more rarely. The mean postoperative DASH score was 61 points. Mean wrist joint mobility was 50 degrees for extension/flexion, and 20 degrees for radial- and ulnar abduction. CONCLUSION: The result of total wrist joint arthroplasty depends very much on a careful patient selection. A preoperative bony malposition of the wrist and a tendon dysfunction seem to be responsible for a bad result. High expectations with regard to range of movement and strength should be avoided. A good reduction of pain can be achieved but the risk of complication is still higher than in arthrodesis.
19365641 Sleep apnea in rheumatoid arthritis patients with occipitocervical lesions: the prevalence 2009 Jun Since sleep apnea is a risk factor for high mortality of rheumatoid arthritis (RA) patients, this study examined the prevalence in RA patients with occipitocervical lesions, and the associated radiographic features. Twenty-nine RA patients requiring surgery for progressive myelopathy due to occipitocervical lesions (3 males, 26 females, average age 65 years) were preoperatively evaluated. Twenty-three (79%) had sleep apnea defined as apnea-hypopnea index >5 events per hour measured by a portable monitoring device, and all of them were classified as the obstructive type. Among gender, age, bone mass index (BMI), and radiographic parameters related to occipitocervical lesions: atlantodental interval (ADI), cervical angles (O/C1, C1/2, and C2/6), and cervical lengths (O-C2 and O-C6), the ADI and cervical lengths were shown to be significantly associated with the presence of sleep apnea by parametric statistical analysis. Since there were positive correlations between the ADI and cervical lengths by Pearson's test, we performed a multivariate logistic regression analysis after adjustment for confounding factors and found that small ADI was the principle parameter associated with sleep apnea. We therefore conclude that the prevalence of sleep apnea is higher than that in a general RA population that was reported previously, and believe that occipitocervical lesions are an independent risk factor for this condition. Small ADI and short neck, secondary to the vertical translocation by RA, may cause obstructive sleep apnea, probably through mechanical or neurological collapse of the upper airway.
20704626 Value of serum and synovial fluid activin A and inhibin A in some rheumatic diseases. 2010 Aug AIM: The purpose of the study is to measure serum and synovial fluid levels of activin A and inhibin A in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and osteoarthritis (OA) and correlate them with disease activity parameters. SUBJECTS AND METHODS: This study included 60 patients with various rheumatic diseases (20 with RA, 20 with SLE and 20 with OA), as well as 10 healthy controls. All of them were subjected to complete history-taking, examination and estimation of disease activity index. The following investigations were done for all subjects: serum and synovial activin A, inhibin A, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-dsDNA and complements 3 and 4. RESULTS: Serum levels of activin A were significantly higher in RA, SLE and OA than controls and in RA and SLE versus OA The mean values of serum inhibin A were significantly higher in all studied groups than controls. Synovial activin A and inhibin A were significantly higher in RA than OA. Positive correlations were found between serum activin A and disease activity parameters of RA. In SLE, positive correlations were found between serum activin A and inhibin A with ESR and SLE Disease Activity Index. CONCLUSIONS: Serum activin A and inhibin A were significantly higher in RA and SLE. Serum levels correlated positively with disease activity parameters of RA and SLE. However, synovial levels were significantly higher in RA than OA but showed no correlation or negative correlation with disease activity. We recommend further studies to detect the exact role of activin A and inhibin A in these conditions.
19170214 Spectrum of fibrosing diffuse parenchymal lung disease. 2009 Feb The interstitial lung diseases are a heterogeneous group of disorders characterized by inflammation and/or fibrosis of the pulmonary interstitium. In 2002, the American Thoracic Society and the European Respiratory Society revised the classification of interstitial lung diseases and introduced the term diffuse parenchymal lung disease. The idiopathic interstitial pneumonias are a subtype of diffuse parenchymal lung disease. The idiopathic interstitial pneumonias are subdivided into usual interstitial pneumonia (with its clinical counterpart idiopathic interstitial pneumonia), nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis interstitial lung disease, and lymphocytic pneumonia. Sarcoidosis and hypersensitivity pneumonitis are the 2 most common granulomatous diffuse parenchymal lung diseases. Rheumatoid arthritis, systemic sclerosis, and dermatomyositis/polymyositis (causing antisynthetase syndrome) are diffuse parenchymal lung diseases of known association because these conditions are associated with connective tissue disease. Hermansky-Pudlak syndrome is a rare genetic diffuse parenchymal lung disease characterized by the clinical triad of pulmonary disease, oculocutaneous albinism, and bleeding diathesis. This review provides an overview of the chronic fibrosing diffuse parenchymal lung diseases. Its primary objective is to illuminate the clinical challenges encountered by clinicians who manage the diffuse parenchymal lung diseases regularly and to offer potential solutions to those challenges. Treatment for the diffuse parenchymal lung diseases is limited, and for many patients with end-stage disease, lung transplantation remains the best option. Although much has been learned about the diffuse parenchymal lung diseases during the past decade, research in these diseases is urgently needed.
20201074 The proinflammatory activity of recombinant serum amyloid A is not shared by the endogenou 2010 Jun OBJECTIVE: Elevated serum levels of the acute-phase protein serum amyloid A (SAA) are a marker for active rheumatoid arthritis (RA), and SAA can also be found in the tissues of patients with active RA. Based on a number of studies with recombinant SAA (rSAA), the protein has been suggested to be a potent proinflammatory mediator that activates human neutrophils, but whether endogenous SAA shares these proinflammatory activities has not been directly addressed. The present study was undertaken to investigate whether SAA in the plasma of patients with RA possesses proinflammatory properties and activates neutrophils in a manner similar to that of the recombinant protein. METHODS: Neutrophil activation was monitored by flow cytometry, based on L-selectin shedding from cell surfaces. Whole blood samples from healthy subjects and from RA patients with highly elevated SAA levels were studied before and after stimulation with rSAA as well as purified endogenous SAA. RESULTS: Recombinant SAA potently induced cleavage of L-selectin from neutrophils and in whole blood samples. Despite highly elevated SAA levels, L-selectin was not down-regulated on RA patient neutrophils as compared with neutrophils from healthy controls. Spiking SAA-rich whole blood samples from RA patients with rSAA, however, resulted in L-selectin shedding. In addition, SAA purified from human plasma was completely devoid of neutrophil- or macrophage-activating capacity. CONCLUSION: The present findings show that rSAA is proinflammatory but that this activity is not shared by endogenous SAA, either when present in the circulation of RA patients or when purified from plasma during an acute-phase response.
20493226 Expression and function of the P2X(7) purinergic receptor in patients with systemic lupus 2010 Aug Because the synthesis of pro-inflammatory cytokines and apoptosis of lymphoid cells can be induced through P2X(7), we decided to study its expression, function (apoptosis, shedding of CD62L and synthesis of IL-1beta induced by ATP) and genetic polymorphisms (1513 AC and -762 T/C) in peripheral blood mononuclear cells from 101 patients with systemic lupus erythematosus (SLE), 122 with rheumatoid arthritis (RA) and 90 healthy controls. We found no significant differences in the distribution of 1513 and -762 genotypes of P2X(7) gene in SLE or RA patients compared with healthy controls. However, a diminished induction of apoptosis of CD4(+) T lymphocytes and monocytes was observed in SLE patients with the 1513 AC genotype, and the release of IL-1beta upon stimulation with ATP was significantly decreased in SLE patients. In contrast, in RA patients we detected that the release of IL-1beta was increased. In addition, in patients with SLE and RA the SNPs 1513 AC was associated with a low expression of P2X(7). These results suggest a possible involvement of P2X(7) in the pathogenesis of inflammatory autoimmune diseases.
20506304 Anti-apolipoprotein A-1 IgG predicts major cardiovascular events in patients with rheumato 2010 Sep OBJECTIVE: To determine whether anti-apolipoprotein A-1 (anti-Apo A-1) IgG are associated with major cardiovascular events in patients with rheumatoid arthritis (RA). METHODS: We determined anti-Apo A-1 IgG levels and the concentrations of cytokines, oxidized low-density lipoprotein (LDL), and matrix metalloproteinase 1 (MMP-1) MMP-2, MMP-3, and MMP-9 in sera from 133 patients with RA who did not have cardiovascular disease at baseline, all of whom were longitudinally followed up over a median period of 9 years. A major cardiovascular event was defined as a fatal or nonfatal stroke or acute coronary syndrome. The proinflammatory effects of anti-Apo A-1 IgG were assessed on human macrophages in vitro. RESULTS: During followup, the overall incidence of major cardiovascular events was 15% (20 of 133 patients). At baseline, anti-Apo A-1 IgG positivity was 17% and was associated with a higher incidence of major cardiovascular events (adjusted hazard ratio 4.2, 95% confidence interval 1.5-12.1). Patients who experienced a subsequent major cardiovascular event had higher circulating levels of anti-Apo A-1 IgG at baseline compared with those who did not have a major cardiovascular event. Receiver operating curve analysis showed that anti-Apo A-1 IgG was the strongest of all tested biomarkers for the prediction of a subsequent major cardiovascular event, with an area under the curve value of 0.73 (P = 0.0008). At the predefined and previously validated cutoff levels, the specificity and sensitivity of anti-Apo A-1 IgG to predict major cardiovascular events were 50% and 90%, respectively. Anti-Apo A-1 IgG positivity was associated with higher median circulating levels of interleukin-8 (IL-8), oxidized LDL, and MMP-9 and higher proMMP-9 activity as assessed by zymography. On human macrophages, anti-Apo A-1 IgG induced a significant dose-dependent increase in IL-8 and MMP-9 levels and proMMP-9 activity. CONCLUSION: Anti-Apo A-1 IgG is an independent predictor of major cardiovascular events in RA, possibly by affecting vulnerability to atherosclerotic plaque.
19644853 Determinants of red blood cell methotrexate polyglutamate concentrations in rheumatoid art 2009 Aug OBJECTIVE: Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug (DMARD) in the management of rheumatoid arthritis (RA). MTX is transported into cells, where additional glutamate moieties are added and it is retained as MTX polyglutamates (MTXGlu [referred to as a group as MTXGlun]). There is large interpatient variability in MTXGlun concentrations. This study was undertaken to determine nongenetic factors that influence red blood cell (RBC) MTXGlun concentrations in patients receiving long-term stable low-dose oral MTX. METHODS: One hundred ninety-two patients receiving long-term oral MTX for the treatment of RA were recruited. Trough MTXGlun concentrations were measured by high-performance liquid chromatography. Univariate analysis was performed to determine variables influencing MTXGlun concentrations. Backward stepwise multivariate regression analysis was done to determine variables that affect individual MTXGlun concentrations; variables with P values of <0.1 in the univariate analysis for any MTXGlun were included. RESULTS: Univariate analysis revealed that increased age, lower estimated glomerular filtration rate (GFR), higher MTX dosage, longer duration of MTX treatment, and use of prednisone were associated with significantly higher MTXGlun concentrations. Smokers had significantly lower concentrations of MTXGlu3, MTXGlu3-5, and MTXGlu1-5. Sex, rheumatoid factor and anti-cyclic citrullinated peptide status, RBC folate level, and body mass index had no significant effect on MTXGlun levels. Concomitant use of other DMARDs was associated with lower MTXGlu2 levels, and treatment with nonsteroidal antiinflammatory drugs was associated with lower MTXGlu3 and MTXGlu1-5 concentrations. Multivariate regression analysis revealed that age, MTX dosage, and estimated GFR were the major determinants of MTXGlun concentrations. CONCLUSION: Large interpatient variability in MTXGlun concentrations can be explained, at least in part, by a combination of factors, particularly age, MTX dosage, and renal function. There are complex interactions between smoking, RBC folate levels, and concentrations of MTXGlun.
19505408 Efficacy and safety of anti-TNF-alpha therapy combined with cyclosporine A in patients wit 2009 Apr This study further expands our previous observation demonstrating the usefulness of combination therapy of anti-TNF-alpha and cyclosporine A in the treatment of rheumatoid arthritis and concurrent hepatitis C virus infection, as well its efficacy and safety in controlling HCV viremia and liver toxicity. Seven patients were included in the study; transaminase levels remained unchanged, HCV RNA serum levels decreased significantly and DAS 28 significantly improved after twelve month follow-up. No side effects were registered.
20560812 Influence of female hormonal factors, in relation to autoantibodies and genetic markers, o 2010 Nov OBJECTIVES: To study the influence of female hormonal factors on the development of rheumatoid arthritis (RA) in relation to the human leucocyte antigen (HLA)-DRB1 shared epitope (SE), the protein tyrosine phosphatase (PTPN22) 1858T variant, anti-citrullinated protein antibodies (ACPAs), and immunoglobulin (Ig)M-rheumatoid factor (IgM-RF). METHODS: A case-control study (1:4) was nested within the Medical Biobank of northern Sweden. Females who had subsequently developed RA (n = 70), median of 2.7 years before the onset of symptoms, and matched controls (n = 280) were identified from among the blood donors. A questionnaire concerning previous exposures until disease onset, including hormonal and reproductive factors, and smoking habits was distributed. RESULTS: Breastfeeding was significantly associated with the development of RA [odds ratio (OR) 4.8, 95% confidence interval (CI) 1.43-15.8]. Increasing time of breastfeeding increased the risk of RA (OR 5.7, 95% CI 1.83-17.95) for breastfeeding ≥ 17 months. In a multiple logistic regression analysis, increasing time of breastfeeding (OR 9.5, 95% CI 2.14-42.43 for ≥ 17 months), seropositivity for ACPAs (OR 19.5, 95% CI 4.47-84.81), and carriage of the PTPN22 1858T variant (OR 3.2, 95% CI 1.36-7.54) remained significant predictors of RA. Users of oral contraceptives (OC) for ≥ 7 years had a decreased risk for development of RA (OR 0.37, 95% CI 0.15-0.93). CONCLUSIONS: A longer duration of breastfeeding increased the risk of developing RA, especially among individuals seropositive for ACPA or IgM-RF or carrying the PTPN22 1858T variant. Use of OC for ≥ 7 years was associated with a decreased risk.
21131423 Profiling of CD4+ T cells with epigenetic immune lineage analysis. 2011 Jan 1 Proper transcriptional control of pro- and anti-inflammatory responses of the immune system is important for a fine-tuned balance between protection and tolerance. Emerging evidence suggests a key role for epigenetic regulation in governing the Th cell differentiation, where effector cytokines direct the overall immune response. In this study, we describe a method to pinpoint the location of isolated human CD4(+) T cells on any T cell effector axis based on specific CpG methylation of cytokine and transcription factor loci. We apply the method on CD4(+) cells obtained from rheumatoid arthritis and multiple sclerosis patients and show that synovial fluid infiltrating CD4(+) T cells are committed toward both Th1 and regulatory T cell phenotype, whereas the Th2 response is suppressed. Furthermore, we show that the IL-17A gene is regulated by promoter methylation and that Th17 commitment is not a common feature in the inflamed joints of rheumatoid arthritis patients. We conclude that the method described in this paper allows for accurate profiling of Th lineage commitment in ex vivo-isolated CD4(+) T cells.
19862529 Recurrent pneumothorax associated with pulmonary nodules after leflunomide therapy in rheu 2011 Jul Rheumatoid arthritis (RA) is a multisystem inflammatory disease characterized by destructive synovitis and systemic extraarticular involvement. One of the most common pulmonary manifestations of RA is rheumatoid nodule. Spontaneous pneumothorax also very rare pulmonary finding and could be associated with pulmonary nodules. Antirheumatic drugs, methotrexate, leflunomide (LEF), infliximab and etanercept, were known as risk factors for developing rheumatoid nodule. However, there was no case report of rheumatoid nodule-associated pneumothorax with the use of LEF. We report, first, herein a case of 46-year-old woman with RA who suffered recurrent spontaneous pneumothorax associated with multiple bilateral subpleural cavitary nodules during treatment with LEF. We reviewed the cases of LEF-related pulmonary nodules developed in patients with RA. Thus, we suggested that pneumothorax can be a rare respiratory fatal complication in patients with RA with pulmonary nodules and LEF can be a rare cause of these manifestations.
19695086 Improving healthcare consumer effectiveness: an Animated, Self-serve, Web-based Research T 2009 Aug 20 BACKGROUND: People with rheumatoid arthritis (RA) should use DMARDs (disease-modifying anti-rheumatic drugs) within the first three months of symptoms in order to prevent irreversible joint damage. However, recent studies report the delay in DMARD use ranges from 6.5 months to 11.5 months in Canada. While most health service delivery interventions are designed to improve the family physician's ability to refer to a rheumatologist and prescribe treatments, relatively little has been done to improve the delivery of credible, relevant, and user-friendly information for individuals to make treatment decisions. To address this care gap, the Animated, Self-serve, Web-based Research Tool (ANSWER) will be developed and evaluated to assist people in making decisions about the use of methotrexate, a type of DMARD. The objectives of this project are: 1) to develop ANSWER for people with early RA; and 2) to assess the extent to which ANSWER reduces people's decisional conflict about the use of methotrexate, improves their knowledge about RA, and improves their skills of being 'effective healthcare consumers'. METHODS/DESIGN: Consistent with the International Patient Decision Aid Standards, the development process of ANSWER will involve: 1.) creating a storyline and scripts based on the best evidence on the use of methotrexate and other management options in RA, and the contextual factors that affect a patient's decision to use a treatment as found in ERAHSE; 2.) using an interactive design methodology to create, test, analyze and refine the ANSWER prototype; 3.) testing the content and user interface with health professionals and patients; and 4.) conducting a pilot study with 51 patients, who are diagnosed with RA in the past 12 months, to assess the extent to which ANSWER improves the quality of their decisions, knowledge and skills in being effective consumers. DISCUSSION: We envision that the ANSWER will help accelerate the dissemination of knowledge and skills necessary for people with early RA to make informed choices about treatment and to manage their health. The latest in animation and online technology will ensure ANSWER fills a knowledge translation gap, focusing on the next generation of people living with RA.
20453439 Genetic background of tolerance breakdown in rheumatoid arthritis. 2010 Rheumatoid arthritis (RA) is a complex mutifactorial autoimmune disease. As anti-citrullinated peptide antibodies (ACPA) exhibit unique specificity for RA, breakdown of immunological tolerance to citrullinated self-proteins is considered to be a key feature of RA pathogenesis. While environmental factors such as smoking and viral infections have been implicated in the pathogenesis, recent genome-scans for RA have unraveled multiple genetic factors involved in RA. Some of these genetic factors may specifically contribute to the tolerance breakdown of RA. For instance, PADI4 gene encoding an enzyme that converts arginine residues to citrullines may enhance the production of auto-antigens. These citrullinated proteins are then presented to helper T-cells via HL-DR molecule on the antigen presenting cells, where specific HLA-DRB1 alleles encoding "shared-epitope" have significant relevance to RA. On the other hand, genes regulating the activity of lymphocytes such as PTPN22 and FCRL3 may influence auto-reactivity of individual lymphocytes. Taken together, combination of these genetic factors accelerates autoimmune response in RA.
19765281 Suppressive effect of secretory phospholipase A2 inhibitory peptide on interleukin-1beta-i 2009 INTRODUCTION: Secretory phospholipase A2 (sPLA2) and matrix metalloproteinase (MMP) inhibitors are potent modulators of inflammation with therapeutic potential, but have limited efficacy in rheumatoid arthritis (RA). The objective of this study was to understand the inhibitory mechanism of phospholipase inhibitor from python (PIP)-18 peptide in cultured synovial fibroblasts (SF), and to evaluate its therapeutic potential in a human tumor necrosis factor (hTNF)-driven transgenic mouse (Tg197) model of arthritis. METHODS: Gene and protein expression of sPLA2-IIA, MMP-1, MMP-2, MMP-3, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 were analyzed by real time PCR and ELISA respectively, in interleukin (IL)-1beta stimulated rheumatoid arthritis (RA) and osteoarthritis (OA) synovial fibroblasts cells treated with or without inhibitors of sPLA2 (PIP-18, LY315920) or MMPs (MMP Inhibitor II). Phosphorylation status of mitogen-activated protein kinase (MAPK) proteins was examined by cell-based ELISA. The effect of PIP-18 was compared with that of celecoxib, methotrexate, infliximab and antiflamin-2 in Tg197 mice after ip administration (thrice weekly for 5 weeks) at two doses (10, 30 mg/kg), and histologic analysis of ankle joints. Serum sPLA2 and cytokines (tumor necrosis factor (TNF)alpha, IL-6) were measured by Escherichia coli (E coli) assay and ELISA, respectively. RESULTS: PIP-18 inhibited sPLA2-IIA production and enzymatic activity, and suppressed production of MMPs in IL-1beta-induced RA and OA SF cells. Treatment with PIP-18 blocked IL-1beta-induced p38 MAPK phosphorylation and resulted in attenuation of sPLA2-IIA and MMP mRNA transcription in RA SF cells. The disease modifying effect of PIP-18 was evidenced by significant abrogation of synovitis, cartilage degradation and bone erosion in hTNF Tg197 mice. CONCLUSIONS: Our results demonstrate the benefit that can be gained from using sPLA2 inhibitory peptide for RA treatment, and validate PIP-18 as a potential therapeutic in a clinically relevant animal model of human arthritis.
19949742 A case of tuberculous arthritis following the use of etanercept. 2009 Dec Etanercept is a tumor necrosis factor (TNF) inhibitor that has been used for the treatment of chronic inflammatory diseases including rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Because of its immunosuppressive activity, opportunistic infections have been noted in treated patients, most notably caused by Mycobacterium tuberculosis. Tuberculosis may present in an extrapulmonary or disseminated form. Since TNF-alpha inhibitors have been used in Korea, a few cases of TNF-alpha inhibitor associated tuberculosis have been described. However, tuberculous arthritis has not been previously reported. We describe a case of tuberculous arthritis in a 57-year-old woman with rheumatoid arthritis who was treated with etanercept.
19160281 Dietary interventions for rheumatoid arthritis. 2009 Jan 21 BACKGROUND: The question of what potential benefits and harms are associated with certain dietary regimes used in rheumatoid arthritis is an important one for many patients and health care providers. OBJECTIVES: To assess the effectiveness and safety of dietary interventions in the treatment of rheumatoid arthritis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL)(The Cochrane Library, issue 1 2008), MEDLINE, EMBASE, AMED, CINAHL and reference lists of relevant articles (up to January 2008), and contacted authors of included articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) where the effectiveness of dietary manipulation was evaluated. Dietary supplement studies (including fish oil supplements) were not included. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion, assessed the internal validity of included trials and extracted data. Investigators were contacted to obtain missing information. MAIN RESULTS: Fourteen RCTs and one CCT, with a total of 837 patients, were included. Due to heterogeneity of interventions and outcomes, baseline imbalance and inadequate data reporting, no overall effects were calculated. A single trial with a moderate risk of bias found that fasting, followed by 13 months on a vegetarian diet, may reduce pain (mean difference (MD) on a 0 to 10 scale -1.89, 95% confidence interval (CI) -3.62 to -0.16), but not physical function or morning stiffness immediately after intervention. Another single trial with a moderate risk of bias found that a 12-week Cretan Mediterranean diet may reduce pain (MD on a 0 to 100 scale -14.00, 95% CI -23.6 to -4.37), but not physical function or morning stiffness immediately after intervention. Two trials compared a 4-week elemental diet with an ordinary diet and reported no significant differences in pain, function or stiffness. Due to inadequate data reporting, the effects of vegan and elimination diets are uncertain. When comparing any dietary manipulation with an ordinary diet we found a significantly higher total drop-out of 10% (risk difference (RD) 0.10, 95% CI 0.02 to 0.18), higher treatment-related drop-out of 5% (RD 0.05, 95% CI -0.03 to 0.14) and a significantly higher weight loss (weighted mean difference -3.23, 95% CI -4.79 to -1.67 kg) in the diet groups compared to the control groups. AUTHORS' CONCLUSIONS: The effects of dietary manipulation, including vegetarian, Mediterranean, elemental and elimination diets, on rheumatoid arthritis are still uncertain due to the included studies being small, single trials with moderate to high risk of bias. Higher drop-out rates and weight loss in the groups with dietary manipulation indicate that potential adverse effects should not be ignored.