Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
16265689 Staphylococcus aureus in patients with rheumatoid arthritis under conventional and anti-tu 2005 Nov OBJECTIVE: To compare the prevalence of nasal and oral Staphylococcus aureus in patients with rheumatoid arthritis (RA) with the prevalence in controls with other rheumatic diseases, and to determine predictors of S. aureus carriage and the influence of treatment with anti-tumor necrosis factor-a (anti-TNF-alpha) agents. METHODS: Eighty-one patients with RA and 83 other control patients of 2 outpatient rheumatology clinics were cultured for nasal and oral carriage of S. aureus. Quantitative nasal cultures for S. aureus were performed from swabs of the anterior nares, the posterior pharynx, and the soft palate. Information on medications, medical conditions, and risk factors for S. aureus carriage was collected from all participants by a questionnaire and confirmed by chart review. RESULTS: The S. aureus carriage rate (nasal and/or oral colonization) was 34.6% among RA patients and 32.5% among controls (p = 0.87). Being treated with an anti-TNF-alpha agent plus methotrexate (MTX) was the only independent predictor of S. aureus carriage (OR 3.24, 95% CI 1.16-9.05, p = 0.025). The S. aureus carriage rate among RA patients treated with an anti-TNF-alpha agent plus MTX was 60% (9/15) versus 23.1% (3/13) in RA patients treated with an anti-TNF-alpha agent only (p = 0.049). All S. aureus isolates were susceptible to oxacillin. CONCLUSION: The S. aureus carriage rate among patients with RA was not higher than among controls. Treatment with anti-TNF-alpha agents was not associated with an increased S. aureus carriage rate. However, treatment with an anti-TNF-alpha agent plus MTX may predispose patients to S. aureus carriage.
16265688 Anti-tumor necrosis factor-alpha therapy augments dipeptidyl peptidase IV activity and dec 2005 Nov OBJECTIVE: To assess the enzymatic activity and biochemical status of dipeptidyl peptidase IV (DPP IV), an enzyme that participates in the degradation of proinflammatory molecules, in sera from a group of patients with rheumatoid arthritis (RA; n = 15) treated with a human anti-tumor necrosis factor-a (anti-TNF-alpha) antibody (adalimumab) for 32 weeks. IgG antibody titers against chaperone Bip (GRP78), phosphoglucose isomerase (PGI), lactate dehydrogenase (LDH), fibronectin (FN), and actin were also studied. METHODS: DPP IV activity was measured in sera using Gly-Pro-p-nitroanilide as substrate. The biochemical profile of circulating DPP IV glycoforms was assessed by isoelectric focusing gel electrophoresis. All IgG autoantibody titers and their sialylation levels were determined by ELISA. RESULTS: Patients showed significant increases in serum DPP IV enzymatic activity from basal values (3.554 +/- 1.096) with respect to those obtained at 32 weeks (4.787 +/- 0.953; p < 0.05). Changes in the biochemical profile of circulating DPP IV from acidic to more neutral isoelectric point glycoforms were also seen during treatment. The elevated titers of anti-GRP78 and anti-PGI IgG observed at the beginning of treatment decreased significantly during therapy, whereas those of anti-LDH, anti-FN, and anti-actin IgG remained unchanged. At the end of treatment, sialylation levels of anti-GRP78 and anti-PGI IgG antibodies increased to nearly normal levels. The DPP IV biochemical changes were accompanied by a significant improvement of the Disease Activity Score (DAS28). CONCLUSION: The reduced activity of DPP IV along with increased titers of circulating antibodies to GRP78 and PGI may play a role in the pathogenesis of RA and can be successfully modified by administration of adalimumab.
14593490 Cytokine profile in serum and synovial fluid of arthritis patients with Chlamydia trachoma 2005 Jan Chlamydia trachomatis (Ct)-induced arthritis (CtIA) is characterized by persistent Ct infection, which stimulates secretion of cytokines in vitro. We therefore investigated whether CtIA patients have a unique cytokine profile in synovial fluid or serum in vivo. Because underlying Ct infection is overlooked in a high percentage of patients with initially diagnosed undifferentiated oligoarthritis (UOA), we examined whether determination of cytokines might also be of diagnostic relevance for this arthritis form. Matched serum and synovial fluid specimens from 26 patients with CtIA were analyzed and compared to those from 34 patients with UOA in whom Ct infection was excluded and those of nine patients with rheumatoid arthritis (RA). In 15 CtIA patients, Ct DNA from synovial fluid could be amplified by polymerase chain reaction. The following cytokine or cytokine antagonists were measured by enzyme-linked immunosorbent assay: interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-6, IL-1 receptor antagonist, and soluble TNF receptor p75. No statistically significant differences in cytokine levels between patients with CtIA or the other arthritis forms were detected. Also, comparison between CtIA patients with (n = 17) and without Chlamydia DNA (n = 9) in synovial fluid revealed no significant differences for these cytokines. Cytokine levels in serum and synovial fluid were not different between CtIA, UOA without Ct infection, and RA patients. The intracellular presence of Ct was not associated with a specific profile of these cytokines in vivo.
16999275 [Rheumatic diseases as risk factors for cardiovascular disease]. 2006 Sep 2 Cardiovascular disease is the leading cause of death in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE). In addition to mortality, cardiovascular morbidity is also markedly increased in these patients, compared with the general population. The increased cardiovascular risk can be explained only partially by an increased prevalence of classical risk factors for cardiovascular disease; it also appears to be related to inflammation. Prospective intervention trials aimed at the modification of cardiovascular risk factors are needed to determine the impact of cardiovascular risk reduction in patients with rheumatic disease. In addition to SLE, RA and AS should be acknowledged as new risk factors for cardiovascular disease.
16142848 Alfacalcidol versus plain vitamin D in inflammation induced bone loss. 2005 Sep Inflammatory diseases lead to systemic osteoporosis. Causal factors include increased circulating concentrations of inflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), glucocorticoid medication, and reduced physical activity. In addition, disturbances of vitamin D metabolism play an important role for the development of inflammation induced osteoporosis. Therefore, D-hormone analogs offer an important treatment option. 1,25-dihydroxyvitamin D (D-hormone) prevented bone loss in the rat model of inflammation mediated osteopenia and in an arthritis model. One explanation is that animals and humans with inflammatory diseases exhibit markedly reduced circulating concentrations of D-hormone, partly the result of inhibition of renal 1-alpha-hydroxylase by TNF-alpha. In addition, the number of vitamin D receptors is reduced by glucocorticoids. Moreover, D-hormone has pleiotropic effects not only on calcium homoeostasis but also on muscle (improving power), the nervous system, and the immune system. D-hormone inhibits the release of cytokines (IL-1, IL-6, TNF-alpha) from macrophages and stimulates osteoprotegerin secretion in vitro and improves arthritis in animal models. This article reviews the interaction between inflammatory disease and vitamin D metabolism, summarizes the rationale for the therapeutic use of alfacalcidol, and provides recent data from controlled clinical trials comparing the effect of alfacalcidol versus plain vitamin D in secondary osteoporosis. Alfacalcidol, but not plain vitamin D, has pleiotropic effects improving bone and muscle metabolism and clinical symptoms in patients with rheumatoid arthritis.
16164218 [Biological agents targeting on pro-inflammatory cytokines]. 2005 Sep Biological agents targeting on pro-inflammatory cytokines are developed, and provide a great impact on the medical management of rheumatoid arthritis (RA). Particularly, biologics against tumor necrosis factor(TNF) can not only induce great clinical improvement, but also halt structural damage on the joints. Now chimeric anti-TNFalpha monoclonal antibody, infliximab, full human anti-TNFalpha monoclonal antibody, adalimumab, and TNF receptor II (p75) -IgGFc fusion protein, etanercept, are widely used in the inflammatory disorders including RA. This review article shows the characteristics of these anti-TNF biologics on RA, and summarizes the efficacy as well as the safety of the agents.
16038857 Intra- and inter-rater reliability of the anterior atlantodental interval measurement from 2005 Aug An investigation of intra- and inter-rater reliability anterior atlantodental interval (AADI) measurements was conducted using flexion/extension plain radiographs. Flexion and extension lateral radiographs of individuals investigated for atlantoaxial instability were measured for AADI on three occasions. Intra-rater intraclass correlation coefficients (ICC) were calculated for both flexion (0.99) and extension (0.96). Inter-rater ICCs were 0.93 and 0.84 for flexion and extension, respectively. The AADI measurement proved to be reproducible with a minimal standard of error, between and within raters.
16211246 The exploration of joint-specific immunoreactions on immunoglobulins G of anti-glucose-6-p 2005 Nov The pathogenic role of autoantibodies in rheumatoid arthritis (RA) remains elusive. Anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) are candidates for arthritogenic Abs because they directly induce arthritis in mice. High titers of anti-GPI Abs are found in some RA patients with severe forms. The aim of this study was to analyze the role of IgG, including anti-GPI Abs, in the joints of RA patients. Synovial tissue was obtained from 6 patients with RA (3 anti-GPI Abs- positive and 3 anti-GPI Abs- negative) and compared histologically and immunohistochemically for IgG and C3 deposition. IgG fractions were separated from the sera of anti-GPI Abs-positive RA patients and healthy subjects, and injected into the metacarpophalangeal joints of 4 cynomolgus monkeys. On day 16, the joints were harvested and examined histologically and immunohistochemically. The expression of the C5a receptor (C5aR) molecule in the synovium was quantified by real-time PCR using cDNA from the monkeys' joints. The synovia of anti-GPI Abs-positive RA patients showed diffuse infiltration of cells, including mast cells, and strong deposition of IgG and C3. In monkeys, IgG from RA patients, including anti-GPI Abs, resulted in recruitment of granulocytes and mononuclear cells, strong deposition of IgG on the articular surface, and overexpression of C5aR, but no joint swelling. No infiltrated cells or IgG deposition were observed in monkeys injected with IgGs from healthy subjects. Our results suggest that IgG fraction from RA patients, including that of anti-GPI Abs, may play a role in the synovitis of RA, although the pathogenesis of human anti-GPI Abs is still uncertain.
16142732 RNA released from necrotic synovial fluid cells activates rheumatoid arthritis synovial fi 2005 Sep OBJECTIVE: To assess the expression of Toll-like receptor 3 (TLR-3) protein in synovial tissues and cultured synovial fibroblasts obtained from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to investigate the consequences of stimulation of cultured synovial fibroblasts with TLR-3 ligands. METHODS: TLR-3 expression in synovial tissues was determined by immunohistochemistry and immunofluorescence, and expression in cultured RA synovial fibroblasts (RASFs) was determined by fluorescence-activated cell sorting and real-time polymerase chain reaction techniques. TLR-3 signaling was assessed by incubating RASFs with poly(I-C), lipopolysaccharide, palmitoyl-3-cysteine-serine-lysine-4, or necrotic synovial fluid cells from RA patients in the presence or absence of hydroxychloroquine or Benzonase. Subsequent determination of interferon-beta (IFNbeta), CXCL10, CCL5, and interleukin-6 (IL-6) protein production in the culture supernatants was performed by enzyme-linked immunosorbent assays. RESULTS: TLR-3 protein expression was found to be higher in RA synovial tissues than in OA synovial tissues. TLR-3 expression was localized predominantly in the synovial lining, with a majority of the TLR-3-expressing cells coexpressing fibroblast markers. Stimulation of cultured RASFs with the TLR-3 ligand poly(I-C) resulted in the production of high levels of IFNbeta, CXCL10, CCL5, and IL-6 protein. Similarly, coincubation of RASFs with necrotic synovial fluid cells from patients with RA resulted in up-regulation of these cytokines and chemokines in a TLR-3-dependent manner. CONCLUSION: Our findings demonstrate the expression of TLR-3 in RA synovial tissue and the activation of RASFs in vitro by the TLR-3 ligand poly(I-C) as well as by necrotic RA synovial fluid cells, and indicate that RNA released from necrotic cells might act as an endogenous TLR-3 ligand for the stimulation of proinflammatory gene expression in RASFs.
16788406 Subacromial space measurement: a reliable method indicating fatty infiltration in patients 2006 Oct Proximal migration of the humeral head is thought to indicate fatty infiltration of the rotator cuff muscles or rotator cuff tears. We sought to evaluate the influence of these rotator cuff abnormalities on the subacromial space. Using anteroposterior radiographs, ultrasound, and computed tomography, we analyzed 54 shoulders in 29 patients with rheumatoid arthritis. The upward migration index was defined as proximal migration of the humeral head relative to its size. The mean muscle density from computed tomography images was used to indicate fatty infiltration. Fatty infiltration of the infraspinatus muscle showed the strongest correlation with proximal migration. After correcting for age, cuff tears, and rheumatoid disease, the partial correlation coefficient between both remained strong. A subdivision in proximal migration is proposed to screen for rotator cuff abnormalities. A large amount of fatty infiltration was indicated by an upward migration index less than 1.25, a medium amount by an upward migration index between 1.25 to 1.35, and a small amount by an upward migration index greater than 1.35. Measurement of proximal migration using the upward migration index provides a reliable screening method indicating fatty infiltration of the rotator cuff.
15971932 UVR, vitamin D and three autoimmune diseases--multiple sclerosis, type 1 diabetes, rheumat 2005 Nov We review the evidence indicating a possible beneficial role for UVR on three Th1-mediated autoimmune diseases: multiple sclerosis, type 1 diabetes and rheumatoid arthritis in relation to recent developments in photoimmunology. Recent work suggests that UVR exposure may be one factor that can attenuate the autoimmune activity leading to these three diseases through several pathways involving UVB and UVA irradiation, UVR-derived vitamin D synthesis and other routes such as alpha-melanocyte-stimulating hormone, calcitonin gene related peptide and melatonin. Ecological features, particularly a gradient of increasing prevalence of multiple sclerosis and type 1 diabetes with higher latitude, provide some support for a beneficial role of UVR. Analytical studies provide additional support, particularly as low vitamin D has been prospectively associated with disease onset for all three diseases, but are not definitive. Randomized controlled trial data are required. Further, we discuss how associated genetic studies may assist the accumulation of evidence with regard to the possible causal role of low UVR exposure and/or low vitamin D status in the development of these diseases.
17015143 Antiphospholipid antibodies as a possible risk factor for atherosclerosis in patients with 2006 Atherosclerosis shares many similarities with inflammatory and autoimmune diseases, among them rheumatoid arthritis (RA). Anticardiolipin antibodies (aCL) and antibodies against beta2-glycoprotein I (anti-beta2GPI) have been detected in sera of RA patients in several studies. We demonstrated aCL and anti-beta2GPI in a selected group of 70 patients with RA (premenopausal women, non-diabetic, non-hypertensive) and compared them with age- and sex-matched controls. There was a significant higher internal carotid artery intima-media thickness and number of plaques in RA patients compared to controls. aCL of IgG and IgM classes were present in 15.7% of RA patients as compared to 5% in the control group. Thirty percent of RA patients had anti-beta2GPI of IgG, IgM and IgA classes compared to 7.5% in controls. Major differences were seen in IgG and IgA classes. Our results support the idea that aCL and anti-beta2GPI represent an important risk factor for atherosclerosis in RA patients. Elevated levels of phosphatidylserine-dependent antiprothrombin antibodies did not contribute significantly to the general prevalence of antiphospholipid antibodies.
16076882 Tumour necrosis factor antagonists improve disease activity but not arterial stiffness in 2005 Nov OBJECTIVES: Systemic inflammation may play an important role in the accelerated atherosclerosis and increased cardiovascular mortality of rheumatoid arthritis (RA). Atorvastatin reduced arterial stiffness in RA patients after only 6 weeks, an effect that may be partially mediated by the immunomodulatory effects of this drug. Suppression of inflammation with tumour necrosis factor (TNF) antagonists may therefore also improve vascular function in RA; however, TNF antagonists have also been shown to cause or exacerbate congestive heart failure in patients with RA and heart failure. The aim of the present study was to examine the effect of treatment with TNF antagonists on arterial stiffness in RA patients with active disease. METHODS: Fourteen RA patients (age 55.1 +/- 3.8 yr; disease duration 7.9 +/- 1.3 yr) with high disease activity [disease activity score (DAS28) 7.1 +/- 0.3] commencing treatment with TNF antagonists for the first time were studied. Clinical status and arterial stiffness were measured before and after 6 weeks of TNF antagonist therapy (etanercept, adalimumab or infliximab). RESULTS: Arterial stiffness did not change during the study period (the mean augmentation index was 29.1 +/- 2.2% at baseline vs 30.1 +/- 1.8% at week 6; P = 0.504). The DAS28 improved significantly from 7.1 +/- 0.3 to 4.3 +/- 0.4 (P < 0.0001). The erythrocyte sedimentation rate and C-reactive protein [median (range)] were reduced from 44 (12-85) to 15 (3-82) mm/h (P = 0.02) and from 34 (3-95) to 10 (2-61) mg/l (P = 0.007), respectively. CONCLUSIONS: Despite significant reductions in synovitis and inflammatory markers in these RA patients, arterial stiffness was not improved by 6 weeks of treatment with TNF antagonists. This result is of relevance given recent reports of potential adverse cardiovascular effects of TNF antagonists in some RA patients.
16269431 Observational study on efficacy, safety, and drug survival of anakinra in rheumatoid arthr 2006 Jun BACKGROUND: The efficacy and safety of anakinra, a recombinant human interleukin 1 (IL1) receptor antagonist used in rheumatoid arthritis, has been documented in five randomised controlled studies. However, long term post-marketing efficacy data are lacking. OBJECTIVE: To evaluate the efficacy, safety, and drug survival of anakinra in clinical practice. METHODS: All patients with rheumatoid arthritis who started anakinra in six hospitals between May 2002 and February 2004 were included in a two year prospective, in part retrospective, cohort study. Efficacy was assessed using the 28 joint disease activity score (DAS28) and the EULAR response criteria. Safety was evaluated using the common toxicity criteria. Drug survival and prognostic factors were analysed using Kaplan-Meier and Cox proportional hazard analyses. RESULTS: After three months, 55% of the patients (n = 146) showed a response (43% moderate, 12% good). A subset of patients continuing anakinra after 18 months had a sustained clinical response compared with patients who switched to other disease modifying antirheumatic drug treatment (DAS28 improvement, 2.46 v 1.79). Drug survival was 78%, 54%, and 14% after three, six, and 24 months, respectively. The reason for discontinuation was lack of efficacy in 78% and adverse events in 22%. Except for higher drug survival in women (odds ratio = 0.51, 95% confidence interval, 0.27 to 0.97), no prognostic factors were found. Adverse events were reported 206 times in 111 patients, the most common being injection site reactions (36%). Serious adverse events occurred in 12% of the patients, with one classified as related. CONCLUSIONS: The short term efficacy and safety profile of anakinra are comparable to those found in randomised clinical studies. However, the drug survival of anakinra after two years is low, mostly because of lack of efficacy.
17129374 Induction of multiple matrix metalloproteinases in human dermal and synovial fibroblasts b 2006 Infections of body tissue by Staphylococcus aureus are quickly followed by degradation of connective tissue. Patients with rheumatoid arthritis are more prone to S. aureus-mediated septic arthritis. Various types of collagen form the major structural matrix of different connective tissues of the body. These different collagens are degraded by specific matrix metalloproteinases (MMPs) produced by fibroblasts, other connective tissue cells, and inflammatory cells that are induced by interleukin-1 (IL-1) and tumor necrosis factor (TNF). To determine the host's contribution in the joint destruction of S. aureus-mediated septic arthritis, we analyzed the MMP expression profile in human dermal and synovial fibroblasts upon exposure to culture supernatant and whole cell lysates of S. aureus. Human dermal and synovial fibroblasts treated with cell lysate and filtered culture supernatants had significantly enhanced expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-10, and MMP-11 compared with the untreated controls (p < 0.05). In the S. aureus culture supernatant, the MMP induction activity was identified to be within the molecular-weight range of 30 to >50 kDa. The MMP expression profile was similar in fibroblasts exposed to a combination of IL-1/TNF. mRNA levels of several genes of the mitogen-activated protein kinase (MAPK) signal transduction pathway were significantly elevated in fibroblasts treated with S. aureus cell lysate and culture supernatant. Also, tyrosine phosphorylation was significantly higher in fibroblasts treated with S. aureus components. Tyrosine phosphorylation and MAPK gene expression patterns were similar in fibroblasts treated with a combination of IL-1/TNF and S. aureus. Mutants lacking staphylococcal accessory regulator (Sar) and accessory gene regulator (Agr), which cause significantly less severe septic arthritis in murine models, were able to induce expression of several MMP mRNA comparable with that of their isogenic parent strain but induced notably higher levels of tissue inhibitors of metalloproteinases (TIMPs). To our knowledge, this is the first report of induction of multiple MMP/TIMP expression from human dermal and synovial fibroblasts upon S. aureus treatment. We propose that host-derived MMPs contribute to the progressive joint destruction observed in S. aureus-mediated septic arthritis.
17023808 Low frequency of anticyclic citrullinated peptide antibodies in psoriatic arthritis but no 2006 Oct BACKGROUND: Anticyclic citrullinated peptide (anti-CCP) antibodies are highly specific for the diagnosis of rheumatoid arthritis (RA). The clinical distinction between RA and psoriatic arthritis (PsA) is often difficult to establish; therefore, the presence of rheumatoid factor (RF) and anti-CCP antibodies could be useful. Seven percent to 40% of patients with longstanding psoriasis will develop PsA at some point. Therefore, it is important to study the positivity of these antibodies in these two interrelated populations. OBJECTIVE: The aim of this study was to determine the seropositivity of anti-CCP antibodies in patients with psoriasis and PsA and to compare it with that seen in patients with other inflammatory, noninflammatory (osteoarthritis) arthritides and healthy controls. PATIENTS AND METHODS: Serum anti-CCP antibodies were measured in 106 patients with cutaneous psoriasis, 72 patients with PsA, 41 healthy controls (HC), 41 patients with undifferentiated or early inflammatory arthritis (UA), and 41 patients with RA and 41 with osteoarthritis using a commercial second-generation enzyme-linked immunosorbent assay. We considered a positive result to be >20 UI/mL, as recommended by the manufacturer. RESULTS: Of 106 patients with PsA, 55 were women and 51 men. The mean age was 42.87 +/- 17.71 years and the mean disease duration was 5.3 +/- 2.10 years. Anti-CCP antibodies were not present in patients with psoriasis without arthritis. In contrast, 7 of 72 (9.72%) patients with PsA were positive for anti-CCP antibodies with a median titer of 7.16 units. Only one patient with PsA was positive for RF. Most of these patients were female with polyarticular joint involvement. Distal interphalangeal involvement was present in 4 and 2 had dactylitis. We found clear differences when we compared patients with PsA with patients with psoriasis (P = 0.001). Of the 43 patients with UA studies, 4 initially exhibited a low titer positive anti-CCP antibody, and at follow up, another patient developed anti-CCP antibodies and later developed RA. None of the patients with UA developed PsA at 5-year follow up. Thirty-two of the 41 patients had a positive anti-CCP antibody and the mean +/- standard deviation of the anti-CCP units was 80.61 +/- 55.5.2. Six of the 41 (14.6%) patients with osteoarthritis studied had positive anti-CCP with a mean titer of 7.388. None of the healthy controls exhibited positively for anti-CCP antibodies. CONCLUSION: Anti-CCP antibodies may be found in patients with PsA and not in our patients with only cutaneous psoriasis. These antibodies may also be found in some patients with osteoarthritis and rarely in patients with UA; such patients will be of interest to follow prospectively.
17260192 Total hip arthroplasty for rheumatoid arthritis in younger patients: 2,557 replacements in 2006 Dec BACKGROUND: The results of total hip arthroplasty (THA) in young patients with rheumatoid arthritis (RA) have been reported in only a few studies. On a nationwide level, the outcome of THA in these patients is unknown. We evaluated the population-based survival of THA in patients under 55 years of age with RA and factors affecting the survival. PATIENTS: Between 1980 and 2003, 2,557 primary THAs performed for RA in patients less than 55 years of age were reported to the Finnish Arthroplasty Register. RESULTS: Proximally circumferentially porous-coated uncemented stems had a 15-year survival rate of 89% (95% CI 83-94) with aseptic loosening as endpoint. The risk of stem revision due to aseptic loosening was higher with cemented stems than with proximally porouscoated uncemented stems implanted during the same period (RR 2.4; p < 0.001). In contrast, Cox regression analysis showed that the risk of cup revision was significantly higher for all uncemented cup concepts than for all-polyethylene cemented cups with any cup revision as endpoint. There were no significant differences in survival between the THR concepts. INTERPRETATIONS: Uncemented proximally circumferentially porous-coated stems and cemented all-poly-ethylene cups are currently the implants of choice for young patients with RA.
16778393 Disease-specific proteins from rheumatoid arthritis patients. 2006 Jun Rheumatoid arthritis (RA) is a chronic inflammatory disease that mainly destroys cartilages or bones at the joints. This inflammatory disorder is initiated by self-attack using own immune system, but the detail of pathological mechanism is unclear. Features of autoantigens leading to autoimmune disease are also under veil although several candidates including type II collagen have been suggested to play a role in pathogenesis. In this report, we tried to identify proteins responding to antibodies purified from RA patients and screen proteins up-regulated or down-regulated in RA using proteomic approach. Fibronectin, semaphorin 7A precursor, growth factor binding protein 7 (GRB7), and immunoglobulin mu chain were specifically associated with antibodies isolated from RA synovial fluids. In addition, some metabolic proteins such as adipocyte fatty acid binding protein, galectin-1 and apolipoprotein A1 precursor were overexpressed in RA synovium. Also, expression of peroxiredoxin 2 was up-regulated in RA. On the contrary, expression of vimentin was severely suppressed in RA synoviocytes. Such findings might give some insights into understanding of pathological mechanism in RA.
16645972 Leflunomide use and the risk of interstitial lung disease in rheumatoid arthritis. 2006 May OBJECTIVE: Spontaneous reports of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) treated with leflunomide, a disease-modifying antirheumatic drug (DMARD), have been appearing recently. To assess this risk, we conducted a population-based epidemiologic study. METHODS: A cohort of 62,734 patients with RA to whom a DMARD had been dispensed between September 1, 1998 and December 31, 2003 was formed using the PharMetrics claims database. A nested case-control design was used, in which each case of serious ILD requiring hospitalization was matched to 100 controls according to age (calendar time) and equal or greater duration of followup, to estimate adjusted rate ratios (RRs) of serious ILD associated with DMARD use. RESULTS: There were 74 cases of serious ILD, which corresponds to a rate of 8.1 per 10,000 patients per year. The risk of ILD was increased with the use of leflunomide (adjusted RR 1.9 [95% confidence interval (95% CI) 1.1-3.6]). Among subjects with no previous methotrexate use and no history of ILD, the risk associated with leflunomide treatment was not elevated (RR 1.2 [95% CI 0.4-3.1]), but it was elevated among the remaining subjects (RR 2.6 [95% CI 1.2-5.6]). Patients with a history of ILD were twice as likely to have been prescribed leflunomide as any other DMARD. CONCLUSION: The reports of ILD associated with leflunomide use are likely the result of channeling of high-risk patients to leflunomide treatment, particularly those with a history of methotrexate use or preexisting ILD. Patients with no history of ILD and no previous methotrexate use show no excess risk of developing ILD with leflunomide treatment.
16804090 Quest for arthritis-causative genetic factors in the rat. 2006 Oct 3 Experimental rat models of arthritis are extensively studied with a view to understand the genetic underpinnings of rheumatoid arthritis (RA). Genome scans using these models have led to the detection of arthritis regulatory quantitative trait loci (QTLs) on all but three chromosomes of the rat. Whereas some of the QTLs are model specific, others overlap between models. Some arthritis susceptibility and/or severity QTLs identified by genetic linkage analyses are corroborated by substitution mapping using congenic strains, whereas others are not. In these cases, testing alternate arthritis models proved to be useful to identify QTL effects. Nevertheless, development and testing of congenic substrains containing progressively shorter introgressed regions have not only fine mapped the location of the arthritis QTLs but also resulted in the identification of multiple QTLs within several originally identified individual QTL. Most of these studies progressed rapidly since 2001, when the rat genome sequence was published. Proof of principle for substitution mapping as a successful method for QTL gene discovery is provided by the positional cloning of Ncf1 as one of the arthritis QTLs in rats. This finding is encouraging for similar sustained dissection of all the other arthritis QTLs mapped in the rat. Identification of rat arthritis QTLs is expected to pave the way for discovery of yet-unidentified arthritis-causative genetic elements and/or pathways for RA in humans and potential development of targeted therapeutics. This review catalogs some of the recent advances made in QTL discovery projects of experimentally induced rat models of arthritis.