Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 17075826 | Investigation of the MHC2TA gene, associated with rheumatoid arthritis in a Swedish popula | 2006 Nov | OBJECTIVE: A recent study of rheumatoid arthritis (RA) showed an association with a functional single-nucleotide polymorphism (SNP) mapping to the promoter region of the MHC2TA gene on chromosome 16p13 in a Swedish population. Interestingly, evidence for linkage to this region has been detected previously in a subgroup of UK RA families carrying 2 copies of shared epitope (SE) alleles. Therefore, we undertook this study to investigate the association of the MHC2TA gene promoter with RA in a UK Caucasian population. METHODS: Association with 5 SNPs spanning the promoter region of the MHC2TA gene was investigated in 813 UK RA patients and 532 population controls. Association with a functional putative RA-causal polymorphism (-168*G/A [rs3087456]) was tested in a total of 1,401 UK RA patients and 2,475 controls. Genotyping was performed using a Sequenom MassArray platform. Estimated haplotype frequencies were generated using the expectation-maximization algorithm and compared between patients and controls. RESULTS: All SNPs were in Hardy-Weinberg equilibrium. No evidence for association was found, either with the putative RA-causal polymorphism (-168*G/A) or with the other SNPs tested. Haplotype analysis revealed extensive linkage disequilibrium across the promoter region but no evidence for association. Stratifying the data set by carriage of SE alleles did not alter the conclusions. CONCLUSION: A functional polymorphism of the MHC2TA gene locus previously associated with RA in a European population has not been associated with RA in a UK population. These findings do not provide support for the notion that this gene plays a major role in the etiology of RA. | |
| 18231792 | Expression of heat shock protein receptors on fibroblast-like synovial cells derived from | 2008 Jul | We examined the membrane expression of inducible Hsp70 and HSP receptors like TLR2, TLR4, CD14, CD36, CD40 and CD91 on fibroblast-like synovial cells (SC) derived from synovial tissue in 23 patients with rheumatoid arthritis (RA), who underwent synovectomy by using flow cytometric analysis. For comparison, autologous skin fibroblasts (SF) derived from the operation wound were tested. Significantly higher Hsp70 expression was found on synovial cells than on skin fibroblasts (median SC 21.4% x SF 5.0%, P < 0.001). Both synovial cells and skin fibroblasts expressed high levels of cell surface CD91 (median SC 80.2% x SF 79.2%), however, no or low levels of CD14, CD40, TLR2, TLR4 and CD36. Further, we observed high co-expression of CD91 and Hsp70 on RA synovial cells (median 18.6%), while skin fibroblasts showed only background Hsp70 expression (median 3.9%, P < 0.001). Since we demonstrated the high prevalence of inducible Hsp70 in RA synovial fluids, we speculate that Hsp70 might be captured onto the membrane of synovial cells from the extracellular space via the CD91 receptor. The significance of the Hsp70 interaction with synovial cells via CD91 remains undefined, but may mediate other non-immune purposes. | |
| 18162709 | Meta-analysis of the association between HLA-DRB1 allele and rheumatoid arthritis suscepti | 2007 Dec | The aims of this study were to summarize results on the association of HLA-DRB1 with rheumatoid arthritis (RA) in Asians and to determine if the shared epitope (SE) hypothesis could explain the meta-analysis results. Among the papers published between January 1987 and July 2006 on RA susceptibility in Asian-Mongoloid populations (Korean, Japanese, Chinese, and Thai), 12 were selected for the metaanalysis. Mongoloid-Asian patients with RA had significantly higher frequencies of HLA-DRB1*0101, *0401, *0410, and *1001 than controls (OR 1.5-2.1, p<0.05 for association). When analyses were restricted to more ethnically homogeneous populations, HLA-DRB1*0405 showed a significant susceptibility to RA in Koreans (OR 5.65, 95% CI 4.32-7.39), whereas the HLA-DRB1*0301, *0403, *0406, *0701, *1301, and *1405 alleles showed protective association with RA (OR 0.32-0.70, p<0.05 for association). In conclusion, it was found that HLA-DRB1 *0101, *0401, *0405, *0410, and *1001 are susceptible, while HLA-DRB1* 0301, *0403, *0406, *0701, *1301, and *1405 are protective in Asian-Mongoloids. All the RA-associated alleles except DRB1*0301 could be explained by the structural model supporting the SE hypothesis that RA susceptibility is determined by the combination of amino acid residues at HLA-DR beta71 and beta74, not by beta71 alone. | |
| 16893535 | Growth hormone, VEGF and FGF: involvement in rheumatoid arthritis. | 2007 Jan | Adult rheumatoid arthritis (RA), a systemic autoimmune disorder of unknown etiology, is characterized by dysfunctional cellular and humoral immunity, enhanced migration and attachment of peripheral macrophages and pro-inflammatory leukocytes to the synovium and articular cartilage of diarthrodial joints. The progressive destruction of cartilage and bone in RA is a result of elevated pro-inflammatory cytokine gene expression, synovial neovascularization, proteinase-mediated dissolution of articular cartilage matrix and osteoclast-mediated subchondral bone resorption. Juvenile chronic arthritis (JCA) is disease with manifestations similar to adult RA that occurs in childhood. JCA usually causes precocious joint destruction and often also presents with evidence of growth plate anomalies and reduced stature. Three proteins play an integral role in both adult RA and JCA. These are somatotropin (also called pituitary growth hormone (GH)), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). GH is responsible for regulating long bone growth and skeletal maturation through its capacity to stimulate insulin-like growth factor-I (IGF-1) synthesis by hepatocytes. Mechanisms responsible for growth plate disturbances and short stature in children with JCA include deficient GH production, GH-insensitivity resulting from defects in the GH receptor, suppressed IGF-1 synthesis or neutralization of IGF-1 action by IGF-1 binding proteins (IGFBPs). In addition, GH has also been implicated in perpetuating inflammation and pain in adult RA. VEGF has been shown to be the critical angiogenesis factor responsible for vascular proliferation and blood vessel invasion of the synovial lining membrane in RA. Acidic FGF (FGF-1) and basic FGF (FGF-2) have also been implicated in aberrant synoviocyte proliferation (i.e. synovial hyperplasia) and apoptosis resistance in adult RA. | |
| 18256870 | Histological analysis of synovium in cases of effect attenuation associated with inflixima | 2008 Jun | To investigate the histological changes of synovium in cases of effect attenuation occurring after the use of infliximab in the treatment of rheumatoid arthritis (RA), we histologically assessed synovial tissue from ten methotrexate-treated RA patients and 12 infliximab-treated RA patients after arthroscopic synovectomy. The synovium was observed using hematoxylin and eosin (H&E) stain and analyzed immunohistochemically for expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), B-cell transmembrane protein, cluster of differentiation 20 (CD20), nuclear factor kappa B (NFkB), bromodeoxyuridine (BrdU), and vascular endothelial growth factor (VEGF). H&E staining showed significant vascular proliferation in the synovium of the RA patients in the infliximab group (p < 0.05). Immunohistochemical examinations showed that TNF-alpha was completely blocked in patients with effect attenuation who received infliximab (p < 0.05). IL-6 was more strongly expressed in the interstitial cells of synovium of patients who received infliximab than in the cells of patients in the control group (p < 0.05). MMP-3 was expressed on the surface of synovium, and CD20 and BrdU were strongly expressed in the infliximab group compared with the control group (p < 0.05). NFkB was expressed in both groups. VEGF was decreased in the infliximab group compared with control. These findings indicate that the expression pattern of immunohistochemical findings in synovium was changed in effect attenuation cases among RA patients treated with infliximab. | |
| 16906016 | HLA-G 14-bp polymorphism regulates the methotrexate response in rheumatoid arthritis. | 2006 Sep | OBJECTIVE: Methotrexate (MTX) represents the antirheumatic drug mainly used in rheumatoid arthritis (RA). HLA-G antigens are inducible nonclassical major histocompatibility complex class Ib molecules important for maintaining anti-inflammatory conditions. The HLA-G gene is characterized by a deletion/insertion polymorphism of 14 bp that controls specific mRNA stability and protein levels. It has been reported that MTX therapy mediates an increase of interleukin-10-producing cells. This cytokine up-regulates HLA-G expression. For this, we tested the hypothesis of an MTX-mediated HLA-G production and the possible relationship with the HLA-G 14-bp polymorphism. METHODS: Peripheral blood mononuclear cells from healthy individuals and non-MTX-treated RA patients were activated with different MTX concentrations, and soluble HLA-G (sHLA-G) and interleukin-10 production was investigated by specific immunoenzymatic assay. HLA-G 14-bp polymorphism genotyping was performed in healthy individuals and RA patients, defined as 'responders' and 'nonresponders' to the MTX therapy. RESULTS: MTX activation induces the production of sHLA-G molecules. A significant association was observed between the highest sHLA-G1 concentrations and the -14/-14 bp genotype. The analysis of the HLA-G 14-bp polymorphism in MTX-treated RA patients has confirmed an increase of the -14/-14 bp genotype in the responder group (chi=6.12, P=0.02; chi test) (odds ratio=2.46 (95% confidence interval, 1.26-4.84) P=0.009; logistic regression model). CONCLUSION: Our results propose that the MTX induces the production of the anti-inflammatory sHLA-G molecules that concur with the therapy response. Furthermore, the association between -14/-14 bp genotype and MTX clinical outcome proposes this polymorphism as a therapy marker in the early phases of the disease. | |
| 17548643 | Expression and regulation of the metalloproteinase ADAM-8 during human neutrophil pathophy | 2007 Jun 15 | A disintegrin and metalloproteinase domain (ADAM) proteins are a family of transmembrane glycoproteins with heterogeneous expression profiles and proteolytic, cell-adhesion, -fusion, and -signaling properties. One of its members, ADAM-8, is expressed by several cell types including neurons, osteoclasts, and leukocytes and, although it has been implicated in osteoclastogenesis and neurodegenerative processes, little is known about its role in immune cells. In this study, we show that ADAM-8 is constitutively present both on the cell surface and in intracellular granules of human neutrophils. Upon in vitro neutrophil activation, ADAM-8 was mobilized from the granules to the plasma membrane, where it was released through a metalloproteinase-dependent shedding mechanism. Adhesion of resting neutrophils to human endothelial cells also led to up-regulation of ADAM-8 surface expression. Neutrophils isolated from the synovial fluid of patients with active rheumatoid arthritis expressed higher amounts of ADAM-8 than neutrophils isolated from peripheral blood and the concentration of soluble ADAM-8 in synovial fluid directly correlated with the degree of joint inflammation. Remarkably, the presence of ADAM-8 both on the cell surface and in suspension increased the ectodomain shedding of membrane-bound L-selectin in mammalian cells. All these data support a potential relevant role for ADAM-8 in the function of neutrophils during inflammatory response. | |
| 18975042 | Survivorship of 2000 tapered titanium porous plasma-sprayed femoral components. | 2009 Jan | Tapered titanium porous plasma-sprayed components have performed well in primary THA. To confirm the literature at longer followup we retrospectively reviewed all 1639 patients who underwent 2000 THAs in which a specific porous femoral component was used. One hundred fourteen patients (134 hips) were lost to followup leaving a cohort of 1525 patients (1866 THAs). The component is a tapered titanium plasma spray-coated design that remained relatively unchanged since its first implantation except for circumferential proximal porous coating added in 1986 and an offset option added in 1999. Minimum followup was 24 months (average, 119 months; range, 24 to 275 months). To date there have been 39 femoral revisions for an implant survival of 98%. Using the Kaplan-Meier method, cumulative survival with any stem revision as the end point was 98.6% at 5 years, 98.4% at 10 years, 97.1% at 15 years, and 95.5% at 20 years. Using aseptic revision for failure of ingrowth as the endpoint, stem survival was 99.1%. Kaplan-Meier cumulative survival with aseptic revision for failure of ingrowth as the endpoint was 99.4% at 5 years, 99.3% at 10, 15 and 20 years. Harris hip pain and total scores improved. This titanium, porous plasma spray-coated femoral component continues to demonstrate high long-term survival with a low rate of component revision for any reason or aseptic failure of ingrowth. LEVEL OF EVIDENCE: Level IV, therapeutic study (case series). See the Guidelines for Authors for a complete description of levels of evidence. | |
| 18092261 | Infliximab dosage and infusion frequency in clinical practice: experiences in the Stockhol | 2007 Nov | OBJECTIVE: To characterize dosages and frequencies of infliximab in a publicly financed health-care system without administrative restrictions on the use of biologics. METHODS: Data from the Stockholm TNFalpha follow-up registry (STURE) were used. Dosages and frequencies of infliximab were adjusted when clinically indicated. Kaplan-Meier survival function was calculated for maintenance of initial infliximab dosage, initial frequency, and both combined; the influence of baseline characteristics on the adjustments and the effects of these adjustments on clinical outcomes were analysed. All analyses were for patients who continued on therapy only. RESULTS: The 1-year survival on initial infliximab frequency was 96.3+/-1.8%, on initial infliximab dose 70.5+/-4.3%, and on the two combined 68.7+/-4.3% (cumulative survival estimate +/- SE). At 2 years, the corresponding values were 88.1+/-3.4%, 53.4+/-5.1%, and 50.3+/-5.1%, and after 3 years 77.4+/-4.9%, 45.9+/-5.4%, and 41.5+/-5.3%. A higher number of prior disease-modifying anti-rheumatic drugs (DMARDs), use of glucocorticoids, and lower baseline swollen joints counts (SJCs) predicted greater likelihood of later adjustments. Efficacy of dosage increases was modest, as reported previously, while frequency increases appeared more efficacious. CONCLUSION: Infliximab dosages and dosing frequencies are increased frequently in clinical practice: after 3 years, only 42% of patients continued on the original schedule. While frequency increases appear to result in better effect persistence between infusions, the gains from dosage increases are small and may not be better than chance. These data suggest that the total amounts of infliximab needed to obtain satisfactory disease control are greater than the amounts suggested by the original dosing recommendations, and may have bearing on pharmaco-economic issues pertaining to treatment with infliximab and other therapeutic agents. | |
| 16521366 | Biologic therapies in autoimmune diseases. | 2006 Jan | Over the past decade, the treatment of rheumatoid arthritis has been revolutionised by the development of therapies targeted at molecules involved in driving the inflammatory response. This review briefly summarises the established uses of biologic therapies in rheumatoid disease, and outlines other diseases in rheumatology and other fields where biologic agents are finding a role. | |
| 17195186 | Outcomes after switching from one anti-tumor necrosis factor alpha agent to a second anti- | 2007 Jan | OBJECTIVE: Patients with rheumatoid arthritis (RA) who experience treatment failure with one anti-tumor necrosis factor (anti-TNF) agent, due to either inefficacy or toxicity, are frequently switched to a second anti-TNF agent, although the benefits of switching are unknown. The present study was undertaken to compare drug continuation rates between the first course and second course of anti-TNF therapy. METHODS: The study involved a prospective cohort of RA patients from a UK national register of new anti-TNF treatment starts (n = 6,739; 876 starting adalimumab, 2,826 starting etanercept, and starting 3,037 infliximab). Over a mean 15 months of followup, 841 patients stopped taking the first drug due to inefficacy and 1,023 stopped the first drug due to toxicity, of whom 503 and 353, respectively, were switched to a second anti-TNF agent. Kaplan-Meier survival curves were plotted to determine continuation rates for each course, and Cox regression was used to compare each course for the risk of stopping and the reason for stopping (inefficacy or toxicity). RESULTS: Overall, 73% of patients who switched to a second anti-TNF agent remained on the new therapy by the end of followup. First drug discontinuation due to inefficacy was associated with an increased rate of second drug discontinuation due to inefficacy (hazard ratio [HR] 2.7, 95% confidence interval [95% CI] 2.1-3.4) but not toxicity (HR 1.1, 95% CI 0.9-1.5). Similarly, first drug discontinuation due to toxicity was associated with an increased rate of second drug discontinuation due to toxicity (HR 2.3, 95% CI 1.9-2.9) but not inefficacy (HR 1.2, 95% CI 0.8-1.6). CONCLUSION: RA patients who are switched to a second anti-TNF drug have high rates of continuation, although among those who must discontinue treatment, the reasons for stopping a second drug are related to the reasons for stopping the first drug. This large data set from the UK provides the first estimates of the magnitude of these effects in patients with long-standing severe RA. | |
| 16555468 | Intravenous application of omega-3 fatty acids in patients with active rheumatoid arthriti | 2006 Jan | The objective of this work was to assess the therapeutic efficacy and tolerability of intravenously applied n-3-PUFA in patients with active rheumatoid arthritis (RA). Thirty-four patients with active RA [identified as having a DAS28 (disease activity score including a 28 joint count) > 4.0] were enrolled into this 5-wk open pilot study (one group design). From the time of screening (visit 0, or V0), background therapy had to remain unchanged. Patients received 2 mL/kg (= 0.1-0.2 g fish oil/kg) fish oil emulsion intravenously on 7 consecutive days (Visit 1-Visit 2, or V1-V2) in addition to their background therapy. A decrease of the DAS28 > 0.6 at day 8 (Visit 2) was the primary efficacy measure. Moreover, the DAS28 at day 35 (Visit 3, or V3), the modified Health Assessment Questionnaire, the American College of Rheumatology (ACR) response criteria (V2, V3) and the Short Form-36 (V3) were assessed. Thirty-three patients completed the trial. The mean DAS28 at V1 was 5.45;at V2, 4.51 (P < .001 V1-V2) and at V3, 4.73 (P < .001 V1-V3; V2-V3, not significantly different). Of the 34 patients, 56% achieved a reduction of the DAS28 > 0.6 at V2 (mean 1.52); 27% > 1.2. At V3, 41% of the patients showed a DAS28 reduction > 0.6 (mean 1.06), and 36% > 1.2. ACR 20 and 50% responses at V2 were seen in 29 and 12% of patients, respectively; at V3, the comparable values were 18 and 9%, respectively. Overall tolerability was excellent. Intravenous application of n-3-PUFA (as an add-on therapy) was considerably well tolerated and led to improvement of the disease activity status in a reasonable number of RA patients. Future trials are warranted to answer whether the intravenous application of n-3-PUFA constitutes a therapeutic option in RA patients. | |
| 18311788 | Crucial role of the interleukin-6/interleukin-17 cytokine axis in the induction of arthrit | 2008 Mar | OBJECTIVE: To clarify the glucose-6-phosphate isomerase (GPI)-specific CD4+ T cell lineage involved in GPI-induced arthritis and to investigate their pathologic and regulatory roles in the induction of the disease. METHODS: DBA/1 mice were immunized with GPI to induce arthritis. CD4+ T cells and antigen-presenting cells were cocultured with GPI, and cytokines in the supernatant were analyzed by enzyme-linked immunosorbent assay. Anti-interferon-gamma (anti-IFNgamma) monoclonal antibody (mAb), anti-interleukin-17 (anti-IL-17) mAb, or the murine IL-6 receptor (IL-6R) mAb MR16-1 was injected at different time points, and arthritis development was monitored visually. After MR16-1 was injected, percentages of Th1, Th2, Th17, and Treg cells were analyzed by flow cytometry, and CD4+ T cell proliferation was analyzed using carboxyfluorescein diacetate succinimidyl ester. RESULTS: GPI-specific CD4+ T cells were found to be differentiated to Th1 and Th17 cells, but not Th2 cells. Administration of anti-IL-17 mAb on day 7 significantly ameliorated arthritis (P < 0.01), whereas administration of anti-IFNgamma mAb exacerbated arthritis. Neither anti-IL-17 mAb nor anti-IFNgamma mAb administration on day 14 ameliorated arthritis. Administration of MR16-1 on day 0 or day 3 protected against arthritis induction, and MR16-1 administration on day 8 significantly ameliorated existing arthritis (P < 0.05). After administration of MR16-1, there was marked suppression of Th17 differentiation, without an increase in Th1, Th2, or Treg cells, and CD4+ T cell proliferation was also suppressed. CONCLUSION: IL-6 and Th17 play an essential role in GPI-induced arthritis. Since it has previously been shown that treatment with a humanized anti-IL-6R mAb has excellent effects in patients with rheumatoid arthritis (RA), we propose that the IL-6/IL-17 axis might also be involved in the generation of RA, especially in the early effector phase. | |
| 18328146 | Pattern of use, economic burden and vial optimization of infliximab for rheumatoid arthrit | 2008 Jan | OBJECTIVE: The aim of this study was to retrospectively examine the pattern of utilization in clinical practice and the costs of therapy of infliximab in the treatment of refractory rheumatoid arthritis (RA). METHODS: Ninety-five RA patients (22 newly treated and 73 maintenance patients) who received at least one infliximab infusion during a selected observation period of one year were studied. After induction phase, infliximab was given at initial dose of 3 mg/kg every 8 weeks. Based on clinical efficacy measured by Disease Activity Score 28 (DAS 28) index, dose adjustments were performed by increasing pro kg dose and/or reducing infusion interval. Overall one-year's treatment costs were also examined. RESULTS: Sixteen (17%) out of 95 patients discontinued treatment before the end of the study owing to lack of efficacy (15) or adverse events (1). Thirteen (59%) out of 22 newly treated patients experienced treatment escalation in the first year of therapy by increasing dose (13.6%), reducing interval (9%), or both (36.3%). The mean infliximab dose administered to all the patients was 3.57 mg/kg and the mean infusion interval was 50 days. Considering all expenditure items, the mean year treatment cost per patient was euro 8454,65. Infliximab vial optimization allows us to reduce this amount to euro 7505,85, with a significant saving of euro 948,80 per patient/year. CONCLUSIONS: In this observational study, adjustments in infliximab treatment in the first year of therapy were common. Despite dose escalation, the mean dosing schedule does not significantly differ from those recommended in the product label. The cost of treatment could be reduced by using infliximab vial optimization. | |
| 17621733 | Ocular side effects of chloroquine in patients with rheumatoid arthritis, systemic lupus e | 2007 Jan | OBJECTIVE: Ocular complication is a major long term adverse event of chloroquine. The present study was carried out to determine the ocular side effects of chloroquine in patients with rheumatic diseases. MATERIAL AND METHOD: Medical records of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and scleroderma (Scl), who received chloroquine for their treatment, at the Division of Rheumatology, Faculty of Medicine, Chiang Mai University between 1 January 1992 and 31 August 2005 were reviewed. Only patients who were older than 16 years, had a clear total accumulative dose and duration of chloroquine therapy, and a regular ophthalmologic examination by ophthalmologists were included in the present study. RESULTS: One hundred and thirty-nine patients (54, 49, and 36 cases of RA, SLE and Scl, respectively) were studied. Forty-eight patients (34.5%) had ocular adverse effects (retinopathy in 37 and corneal deposition in 13 while two patients had both defects). There was no statistical difference in age, mean lean body weight adjusted daily dose, total dosage, and duration of treatment between those with and without ocular side effects. However those with ocular side effects had significantly lower creatinine clearance (66.9 +/- 26.9 vs 72.3 +/- 20.0 ml/min, p = 0.046). CONCLUSION: Ocular side effects of chloroquine were more common in patients with connective tissue diseases who had decreased creatinine clearance. The use of chloroquine in patients with impaired renal function should be of greater concern. | |
| 18612932 | Neurological and pulmonary adverse effects of subcutaneous methotrexate therapy. | 2008 Jul | We report the case of a patient receiving subcutaneous methotrexate (MTX) treatment for rheumatoid arthritis (RA) who developed a complex pattern of neurological and pulmonary symptoms. Fluctuant dysarthria, magnetic gait, weakness and dysmetria of the lower limbs, as well as symptoms and signs consistent with a diagnosis of pneumonitis started within 6 weeks of initiating MTX treatment and slowly resolved after its discontinuation. This case highlights the fact that even the relatively low doses of MTX in the therapy of RA can produce neurotoxicity, which can become manifest in a broad range of symptoms. | |
| 18509592 | Postoperative results and complications of total elbow arthroplasty in patients with rheum | 2008 | Postoperative results and complications of total elbow arthroplasty (TEA) conducted for rheumatoid arthritis (RA) patients at our institute were studied. Primary TEAs were performed in 72 patients. The mean follow-up period was 3.5 years. Three types of prostheses were implanted: JACE prosthesis in 34 elbows, STABLE prosthesis in 13 elbows, and KUDO prosthesis (type 5) in 32 elbows. The outcome was evaluated by the change in the range of motion and the Japanese Orthopaedic Association functional evaluation score for the elbow joint (JOA score). The arc of motion and the JOA score at discharge and at final examination significantly improved in patients with the three types of prosthesis. The loosening rates for the JACE, STABLE and KUDO prostheses were 15, 23, and 0%, respectively, although the follow-up periods were different. The loosening rate decreased to 2.5% when the humeral component was fixed with cement. Intraoperative fractures occurred in eight (10.1%) elbows and ulnar nerve palsy in six. Deep infection developed in three (4.8%) elbows and was treated by removing the prosthesis. Although there were considerable complications, the marked improvements in pain and function favor TEA in patients with rheumatoid elbow. | |
| 18097068 | IL-17RA and IL-17RC receptors are essential for IL-17A-induced ELR+ CXC chemokine expressi | 2008 Jan 1 | IL-17A is a cytokine secreted by the newly described Th17 cells implicated in rheumatoid arthritis (RA). Less is known about its receptors in synoviocytes. IL-17RA and IL-17RC were found to be overexpressed in RA peripheral whole blood and their expression was detected locally in RA synovium. In vitro, IL-17A synergized with TNF-alpha to induce IL-6, IL-8, CCL-20, and matrix metalloproteinase-3. Using microarrays, a specific up-regulation of Glu-Leu-Arg+ CXC chemokines was observed in IL-17A-treated synoviocytes. Using both posttranslational inhibitions by silencing interfering RNA and extracellular blockade by specific inhibitors, we showed that both IL-17RA and IL-17RC are implicated in IL-17A-induced IL-6 secretion, whereas in the presence of TNF-alpha, the inhibition of both receptors was needed to down-regulate IL-17A-induced IL-6 and CCL-20 secretion. Thus, IL-17A-induced IL-6, IL-8, and CCL20 secretion was dependent on both IL-17RA and IL-17RC, which are overexpressed in RA patients. IL-17A-induced pathogenic effects may be modulated by IL-17RA and/or IL-17RC antagonism. | |
| 18597412 | Comparison of pulmonary abnormalities on high-resolution computed tomography in patients w | 2008 Aug | OBJECTIVE: To identify the predominant radiological abnormalities in the lungs of patients with early rheumatoid arthritis (RA) and in those with longstanding RA. METHODS: We performed high-resolution computed tomography (HRCT) on a total of 126 patients with early RA (n = 65) and longstanding RA (n = 61). The most likely diagnosis for each case was made on the basis of the predominant HRCT findings and their extent in the lungs. Pulmonary function tests were done for RA patients with parenchymal abnormalities. RESULTS: The most frequent finding was bronchial dilatation (41.3%), followed by ground-glass attenuation (27.0%), parenchymal micronodules (15.1%), subpleural micronodules (15.1%), reticulation (11.9%), bronchial wall thickening (11.9%), nodules (10.3%), honeycombing (8.7%), and airspace consolidation (4%). Parenchymal micronodules and bronchial wall thickening, indicative of small airway diseases, were more prominent in the patients with longstanding RA. There were no significant differences in the frequency of interstitial abnormalities such as ground-glass attenuation, reticulation, honeycombing, or consolidation between the 2 groups. We identified 10 patients with bronchiolitis pattern, 11 with nonspecific interstitial pneumonia (NSIP) pattern, 2 with usual interstitial pneumonia (UIP) pattern, and 2 with organizing pneumonia (OP) pattern. Mean values of FEV1/FVC ratio and FEV25-75 were lower in the patients with the bronchiolitis pattern, and DLCO was decreased in the patients with the NSIP or UIP pattern. CONCLUSION: Interstitial abnormalities were frequently observed even in patients with early RA, although most of them had no respiratory symptoms. Bronchiolar abnormalities were associated with the duration of RA. | |
| 17122964 | The active metabolite of leflunomide, A77 1726, increases proliferation of human synovial | 2006 Nov | OBJECTIVE AND DESIGN: Excessive synovial fibroblast (SF) proliferation is detrimental in rheumatoid arthritis. We therefore sought to determine the effects of A77 1726, the active metabolite of leflunomide, on SF proliferation. METHODS: Human SFs were used. Cell proliferation was investigated using MTS assay, by (3)H-thymidine incorporation and cell counts. RESULTS: Whereas A77 1726 alone had no effects, it significantly increased the mitogenic effects of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). Cyclooxygenase inhibition might be at least partly involved, since indomethacin displayed similar effects, and since prostaglandin E2 inhibited SF proliferation. In contrast, the effect of A77 1726 did not appear to be mediated through depletion of the pyrimidine pool or inhibition of tyrosine kinases. CONCLUSION: A77 1726 displays proliferative effects in presence of IL-1beta and TNF-alpha. Further elucidation of involved mechanisms may prove useful for the utilization of leflunomide, the development of related compounds or elaboration of new therapeutic strategies. |