Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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20868308 | Changes in body composition after 2 years with rheumatoid arthritis. | 2011 Mar | OBJECTIVES: Rheumatoid arthritis (RA) is associated with cardiovascular disease (CVD). Possible predictors for CVD are early changes in body composition. We therefore evaluated changes in lean body mass (LBM), lean mass of arms and legs (LMAL), total body fat mass (BFM), and truncal fat distribution (FD) after 2 years with RA and possible predictors. METHODS: We registered 63 (45 women) RA patients with disease duration of ≤ 12 months at baseline and after 2 years. Disease Activity Score using 28 joint counts (DAS28), Health Assessment Questionnaire (HAQ) score, body mass index (BMI), comorbidities, smoking, and medications were recorded. Total and regional lean mass and fat mass were measured with dual energy X-ray absorptiometry (DXA). The data were compared with 63 age- and gender-matched controls. RESULTS: LBM and LMAL at baseline in RA patients were significantly lower in men (p = 0.020 and 0.002, respectively) compared to matched controls. Truncal FD was non-significantly increased in RA patients (women p = 0.133, men p = 0.119). The age-related deterioration with decreased LBM after 2 years (p = 0.002 in women and men) and increased BFM (p < 0.001) and truncal FD (p = 0.020) in women were all significantly less pronounced in RA patients than in matched controls. CONCLUSIONS: In patients with early RA and after initiation of therapy, the age-related deterioration with decreasing LBM and increasing truncal FD was lower than in control subjects in this observational study. These potentially harmful alterations seem to be modifiable factors in patients with early RA. | |
19527463 | Efficacy of high-throughput leukocytapheresis for rheumatoid arthritis with a reduced resp | 2009 Jun | Infliximab (INF), a tumor necrosis factor-alpha (TNF-alpha) inhibitor, is an effective drug for patients with rheumatoid arthritis (RA). However, some patients receive no clinical benefit, or the agents gradually lose their effect. Five sessions of high-throughput leukocytapheresis (LCAP) were given at a frequency of once a week using a Cellsorba CS-180S to four patients with a reduced response to INF. The clinical response to LCAP was evaluated using the 28-joint disease activity score with C-reactive protein (DAS28-CRP) and with the erythrocyte sedimentation rate (DAS28-ESR). DAS28-CRP decreased significantly from 5.8 +/- 0.6 before LCAP to 3.9 +/- 0.7 (P = 0.0182) at 1-2 weeks after completion of five sessions of LCAP, and DAS28-ESR decreased significantly from 6.4 +/- 0.6 to 4.6 +/- 0.5 (P = 0.0267). Moreover, all patients had a moderate response according to the European League Against Rheumatism (EULAR) response criteria. The effect of LCAP continued for at least 6 months after its completion in all patients, with no changes in any of their concomitant drugs, and the effect was maintained for at least 1 year in three of the four patients. These results indicate that LCAP is a useful treatment for RA patients with a reduced response to INF. | |
19781237 | [Semi-constrained total elbow arthroplasty for the treatment of the elbow disorders]. | 2009 Jun 15 | OBJECTIVE: To retrospectively review the results of Coonrad-Morrey semi-constrained total elbow arthroplasty (TEA) for the treatment of different elbow disorders. METHODS: Between December 2003 and April 2008, 30 patients with different kinds of elbow disorders including elbow fracture, non-healing elbow fracture, rheumatoid arthritis and osteoarthritis were treated with TEA using the semi-constrained Coonrad-Morrey elbow replacement prostheses. One patient had bilateral total elbow replacements. There were 22 females and 8 males, with a mean age of 66 years (47 to 78). RESULTS: Twenty patients (21 elbows) were available for review. The average length of follow-up was 35 months (from 12 to 52 months). The mean Mayo elbow performance score was 84 points. Excellent results were achieved in 6 elbows (28%), 11 elbows had good outcome (52%), 2 elbows had improvement (10%), while the other 2 elbows had no improvement (10%). The 2 elbows with distal humeral fractures, had no pain after treatment but developed heterotopic ossification, which caused stiffness and lower the Mayo elbow performance score. One delayed healing of the wound, one patient experienced temporary radial nerve hypesthesia and one elbow showed transparent region around the implant without radiological sign of loosening in the implanted prostheses. CONCLUSIONS: This study reveals good to excellent outcome with the use of semi-constrained TEA for the treatment of rheumatoid arthritis, elbow fracture, osteoarthritis and non-healing elbow fractures in elder patients. The non-healing elbow fractures in elder patients would accompany with severe osteoporosis and comminuted fracture, which would affect the result of open reduction internal fixation. So TEA may be one optimal treatment for these patients. | |
19635578 | NO role of NOS2A susceptibility polymorphisms in rheumatoid arthritis. | 2009 Nov | Nitric oxide has been described as a trigger for the synthesis of proinflammatory mediators and as a cytotoxic molecule with a pivotal role in apoptosis at the joints of rheumatoid arthritis (RA) patients. Polymorphisms in the NOS2A gene, which codes for the inducible nitric oxide synthase [(i)NOS], have been tested for association with several autoimmune diseases such as Crohn's disease or type 1 diabetes. Moreover, the existence of correlated levels of (i)NOS protein and synovial cell apoptosis in RA patients, pointed to NOS2A as a good candidate gene involved in RA predisposition. The role of NOS2A was studied in 405 Spanish RA patients and in 398 ethnically matched healthy controls, through the analysis of five SNPs: two at the NOS2A promoter (rs2779251 and 2779248), other two exonic markers (Asp(346)Asp (rs1137933) and Ser(608)Leu (rs22518)) and the last one located at intron 7 (rs3729508). We also included other two widely-used promoter polymorphisms: the insertion/deletion (TAAA/-) and the (CCTTT)n microsatellite. No individual association of each single-marker or haplotype was found with RA susceptibility. Our data show the low linkage disequilibrium between these NOS2A SNPs and the alleles of the (CCTTT)n microsatellite, corroborating in a Spanish population the observation previously described in British and Gambian population. The present data do not support a causative role of NOS2A polymorphisms in RA predisposition. | |
20572857 | Protein and mucin retention on oral mucosal surfaces in dry mouth patients. | 2010 Jun | Oral homeostasis depends largely on proteins and mucins present in saliva that coat all oral surfaces. The present study compared the protein composition of residual fluid on mucosal surfaces in subjects with normal salivary flow with that of patients with dry mouth caused by salivary hypofunction. Samples of residual mucosal fluid were collected using paper strips and then analysed by protein electrophoresis and immunoblotting. In both patients and controls, residual fluids on mucosal surfaces (except the anterior tongue in control subjects) had higher protein concentrations than unstimulated whole-mouth saliva. High-molecular-weight mucin (MUC5B) was present in greater amounts on the anterior tongue than on other surfaces in control subjects. In dry mouth patients who were unable to provide a measurable saliva sample, MUC5B was often still present on all mucosal surfaces but in reduced amounts on the anterior tongue. The membrane-bound mucin, MUC1, was prominent on buccal and labial surfaces in patients and controls. Statherin was still present on surfaces that were dried to remove salivary fluid, suggesting that it may be adsorbed as a protein pellicle. It is concluded that oral mucosal surfaces in dry mouth patients can retain MUC5B and other salivary proteins, although the functional integrity of these proteins is uncertain. | |
20053277 | A Rac1 inhibitory peptide suppresses antibody production and paw swelling in the murine co | 2010 | INTRODUCTION: The Rho family GTPase Rac1 regulates cytoskeletal rearrangements crucial for the recruitment, extravasation and activation of leukocytes at sites of inflammation. Rac1 signaling also promotes the activation and survival of lymphocytes and osteoclasts. Therefore, we assessed the ability of a cell-permeable Rac1 carboxy-terminal inhibitory peptide to modulate disease in mice with collagen-induced arthritis (CIA). METHODS: CIA was induced in DBA/1 mice, and in either early or chronic disease, mice were treated three times per week by intraperitoneal injection with control peptide or Rac1 inhibitory peptide. Effects on disease progression were assessed by measurement of paw swelling. Inflammation and joint destruction were examined by histology and radiology. Serum levels of anti-collagen type II antibodies were measured by enzyme-linked immunosorbent assay. T-cell phenotypes and activation were assessed by fluorescence-activated cell sorting analysis. Results were analyzed using Mann-Whitney U and unpaired Student t tests. RESULTS: Treatment of mice with Rac1 inhibitory peptide resulted in a decrease in paw swelling in early disease and to a lesser extent in more chronic arthritis. Of interest, while joint destruction was unaffected by Rac1 inhibitory peptide, anti-collagen type II antibody production was significantly diminished in treated mice, in both early and chronic arthritis. Ex vivo, Rac1 inhibitory peptide suppressed T-cell receptor/CD28-dependent production of tumor necrosis factor alpha, interferon gamma and interleukin-17 by T cells from collagen-primed mice, and reduced induction of ICOS and CD154, T-cell costimulatory proteins important for B-cell help. CONCLUSIONS: The data suggest that targeting of Rac1 with the Rac1 carboxy-terminal inhibitory peptide may suppress T-cell activation and autoantibody production in autoimmune disease. Whether this could translate into clinically meaningful improvement remains to be shown. | |
19215933 | Study of the human plasma proteome of rheumatoid arthritis. | 2009 Apr 17 | In this study, we report a combined proteomic and peptidomic analysis of human plasma from patients with rheumatoid arthritis (RA) and controls. We used molecular weight cut-off filters (MWCO: 10kDa) to enrich low-molecular-weight (LMW) peptides from human plasma. The peptide fraction was analyzed without trypsin digestion by capillary reversed-phase high-performance liquid chromatography (HPLC) coupled to a linear ion trap-FT-MS system, which identified 771 unique peptides in the peptidome study (from 145 protein progenitors). An anti-albumin/anti-IgG column was used to remove albumin and immunoglobulin G (IgG) from the human plasma. After that, the albumin/IgG-depleted sample was fractionated into a bound fraction and an unbound fraction on a multi-lectin affinity column (M-LAC). LC-MS analysis of the corresponding tryptic digests identified 308 proteins using the M-LAC approach. Relative differences in the following protein classifications were observed in the RA human plasma samples compared with controls: structural proteins, immuno-related proteins, protease inhibitors, coagulation proteins, transport proteins and apolipoproteins. While some of these proteins/peptides have been previously reported to be associated with RA disease such as calgranulin A, B, C and C-reactive protein, several others were newly identified (such as thymosin beta4, actin, tubulin, and vimentin), which may further the understanding of the disease pathogenesis. Moreover, we have found that the peptidomic and glycoproteomic approaches were complementary and allow a more complete picture of the human plasma proteome which can be valuable in studies of disease etiology. | |
19953077 | [CT imaging features of pulmonary involvement in connective tissue disorders]. | 2009 Nov | Connective tissue disorders correspond to a heterogeneous group of inflammatory diseases characterized by abnormal immune system activity leading to connective tissue alterations in multiple parts of the body. In adults, connective tissue disorders include rheumatoid arthritis, progressive systemic sclerosis, Sjögren syndrome, systemic lupus erythematosus, dermatomyositis and polymyositis, ankylosing spondylitis, and mixed connective tissue disease. Broncho-pulmonary involvement may be variable with involvement of all anatomical components of the lung. Involvement of other intrathoracic structures (pleura, respiratory muscles, heart, rib cage) is frequent. The most specific manifestations include interstitial lung diseases and pulmonary hypertension. During follow-up, progressive respiratory diseases may occur due to the treatment, infections, pulmonary embolism or neoplasms. | |
20604674 | Anti-apoA-1 IgG and oxidized LDL are raised in rheumatoid arthritis (RA): potential associ | 2010 Nov | OBJECTIVE: To determine whether emerging cardiovascular risk factors such as anti-apolipoprotein A-1 (anti-apoA-1) immunoglobulin (Ig)G and oxidized low density lipoprotein (oxLDL) are associated with cardiovascular disease (CVD), carotid intima-media thickness (IMT), and disease activity in rheumatoid arthritis (RA). METHOD: We determined the aforementioned associations in 69 RA patients with disease duration of 5 years and 46 controls matched by age, sex, and smoking status. Anti-apoA-1 IgG and oxLDL were measured by enzyme-linked immunosorbent assay (ELISA). Carotid arteries were examined by ultrasound. Disease Activity Score calculated on 28 joints (DAS28) was used to assess disease activity. RESULTS: CVD prevalence was higher among RA patients than controls (17% vs. 2%, p = 0.01) but there was no difference in IMT (median: 0.67 vs. 0.66, p = 0.33). RA patients had a higher anti-apoA-1 IgG prevalence than controls (20% vs. 0%, p = 0.001). Anti-apoA-1 IgG and oxLDL levels were higher in cases than controls [median: 0.33 vs. 0.175 optical density (OD), p = 0.03; and 121 vs. 37.2 U/L, p = 0.0001, respectively]. Anti-apoA-1 IgG-positive patients had higher levels of oxLDL (median: 140.5 vs. 112 U/L, p = 0.01) than those tested negative. Receiver operating characteristic (ROC) curve analysis showed that only anti-apoA-1 IgG was a modest but significant predictor of CVD [area under the curve (AUC) = 0.65, p = 0.03] in RA patients. oxLDL was significantly associated with RA disease activity, whereas anti-apoA-1 IgG was not. CONCLUSIONS: Anti-apoA-1 IgG could be a marker of CVD in RA, whereas oxLDL levels seem to reflect RA disease activity. Other causes of CVD than a general increase in atherosclerosis (as determined by IMT measurements) including plaque stability may therefore be of importance to explain the increased incidence of CVD in RA. | |
20506288 | Mammalian target of rapamycin signaling is crucial for joint destruction in experimental a | 2010 Aug | OBJECTIVE: Activation of the mammalian target of rapamycin (mTOR) pathway is important for immune cell activation and bone metabolism. To date, the contribution of mTOR signaling to joint inflammation and structural bone and cartilage damage is unknown. The aim of this study was to investigate the potential of inhibiting mTOR as a treatment of inflammatory arthritis. METHODS: Human tumor necrosis factor-transgenic mice in which inflammatory arthritis was developing were treated with 2 different mTOR inhibitors, sirolimus or everolimus. The effects of treatment on clinical disease activity, inflammation, and localized joint and cartilage destruction were studied. In addition, the effects of mTOR inhibition on osteoclast survival and expression of key molecules of osteoclast function were analyzed in vitro. Moreover, synovial tissue from patients with rheumatoid arthritis (RA) was assessed for activation of the mTOR pathway. RESULTS: Inhibition of mTOR by sirolimus or everolimus reduced synovial osteoclast formation and protected against local bone erosions and cartilage loss. Clinical signs of arthritis improved after mTOR inhibition, and histologic evaluation showed a decrease in synovitis. In vitro, mTOR inhibition down-regulated the expression of digestive enzymes and led to osteoclast apoptosis. Moreover, mTOR signaling was shown to be active in the synovial membrane of patients with RA, particularly in synovial osteoclasts. CONCLUSION: Signaling through mTOR is an important link between synovitis and structural damage in inflammatory arthritis. Current pharmacologic inhibitors of mTOR could be effective in protecting joints against structural damage. | |
20597112 | The number of elevated cytokines and chemokines in preclinical seropositive rheumatoid art | 2010 Nov | OBJECTIVE: To evaluate levels of biomarkers in preclinical rheumatoid arthritis (RA) and to use elevated biomarkers to develop a model for the prediction of time to future diagnosis of seropositive RA. METHODS: Stored samples obtained from 73 military cases with seropositive RA prior to RA diagnosis and from controls (mean 2.9 samples per case; samples collected a mean of 6.6 years prior to diagnosis) were tested for rheumatoid factor (RF) isotypes, anti-cyclic citrullinated peptide (anti-CCP) antibodies, 14 cytokines and chemokines (by bead-based assay), and C-reactive protein (CRP). RESULTS: Preclinical positivity for anti-CCP and/or ≥2 RF isotypes was >96% specific for future RA. In preclinical RA, levels of the following were positive in a significantly greater proportion of RA cases versus controls: interleukin-1α (IL-1α), IL-1β, IL-6, IL-10, IL-12p40, IL-12p70, IL-15, fibroblast growth factor 2, flt-3 ligand, tumor necrosis factor α, interferon-γ-inducible 10-kd protein, granulocyte-macrophage colony-stimulating factor, and CRP. Also, increasing numbers of elevated cytokines/chemokines were present in cases nearer to the time of diagnosis. RA patients who were ≥40 years old at diagnosis had a higher proportion of samples positive for cytokines/chemokines 5-10 years prior to diagnosis than did patients who were <40 years old at diagnosis (P < 0.01). In regression modeling using only case samples positive for autoantibodies highly specific for future RA, increasing numbers of cytokines/chemokines were predictive of decreased time to diagnosis, and the predicted time to diagnosis based on cytokines/chemokines was longer in older compared with younger cases. CONCLUSION: Levels of autoantibodies, cytokines/chemokines, and CRP are elevated in the preclinical period of RA development. In preclinical autoantibody-positive cases, the number of elevated cytokines/chemokines is predictive of the time of diagnosis of future RA in an age-dependent manner. | |
19219607 | Serum concentrations of formation (PINP) and resorption (Ctx) bone turnover markers in rhe | 2009 Oct | Joint inflammation in rheumatoid arthritis (RA) induces local periarticular osteoporosis. Generalised bone mineral density (BMD) decrease concerns approximately 50% of rheumatic patients. Both types of bone mass depletion can issue from cytokine-induced (TNF-alpha, IL-1, IL-6) osteoclasts' activation, osteoprotegerin and its ligand's (RANKL) function disorders, patients' immobilisation and glucocorticosteroid (GCS) intake, as well as from hormonal alterations in postmenopausal women, predominate among RA individuals. The aim of the study was to compare serum concentrations of marker of bone formation--serum aminoterminal propeptide of type I collagen (PINP), and bone resorption, carboxy (C) terminal telopeptide (Ctx), bone turnover markers in RA and osteoarthritis (OA) patients and in RA groups of different disease activity, different degree of joint damage and the history of GCS intake. A total of 50 RA female patients and 50 women with knee OA were included in the study. Blood for morphology and biochemistry laboratory tests was taken. Joint X-rays to establish OA and RA diagnosis and the degree of RA progression, as well as DEXA BMD measurements were performed. PINP and Ctx concentrations were assessed. In RA patients the number of swollen and painful joints, the duration of morning stiffness, visual analogue scale values and Waaler-Rose's test activity were recorded. The Disease Activity Index (DAS 28) was counted from the appropriate formula. No differences in bone turnover markers' concentrations were noted neither between RA and OA patients nor between the RA group when compared to the one without the history of GCS use. Bone turnover markers' concentrations in RA were proportional to the number of swollen and painful joints. However, no correlation was found between the markers' concentrations and RA activity assessed by DAS 28 or by laboratory means. Ctx concentrations were higher in patients at II degree joint damage according to Larsen and Dale's than at more advanced stages. Ctx concentrations decreased with the disease duration. Serum morphogenesis and resorption markers' concentrations change in course of RA indicating the decrease in bone metabolic activity with the disease duration and progression. High RA activity and severity correlate with increased markers' levels-the resorption one. The influence of GCS on bone metabolism in RA requires further study. | |
20693270 | CCR5 blockade in rheumatoid arthritis: a randomised, double-blind, placebo-controlled clin | 2010 Nov | OBJECTIVE: C-C chemokine receptor type 5 (CCR5), a chemokine receptor expressed on T cells and macrophages, and its ligands are found in inflamed synovial tissue (ST) of patients with rheumatoid arthritis (RA). The rationale for testing CCR5 blockade in patients with RA was supported by the effects of a CCR5 antagonist in collagen-induced arthritis in rhesus monkeys. The effects of CCR5 blockade in patients with active RA were explored. METHODS: In this phase Ib randomised, placebo-controlled trial, treatment with an oral CCR5 inhibitor (SCH351125) in patients with active RA was evaluated. Clinical efficacy was assessed using European League Against Rheumatism and American College of Rheumatology response criteria. ST biopsies were taken before and after 28 days of treatment, and analysed for CCR5+ cells. In a subset of patients, MRIs of an inflamed joint were obtained before and after treatment. RESULTS: In all, 32 patients were included; 20 received SCH351125 and 12 placebo. Three patients who received SCH351125 did not complete the study due to adverse events; none of these were serious. No improvement was observed in the active treatment group compared to placebo. Results were consistent for clinical evaluation, ST analysis and MRI. CONCLUSION: This proof of concept study does not support the use of CCR5 blockade as a therapeutic strategy in patients with active RA. | |
19877093 | Does rheumatoid arthritis equal diabetes mellitus as an independent risk factor for cardio | 2009 Nov 15 | OBJECTIVE: Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease (CVD), but longitudinal observations are limited and the precise magnitude is unknown. We prospectively assessed the incidence of CVD in patients with RA compared with patients with type 2 diabetes mellitus (DM) and the general population. METHODS: The 3-year incidence rate of CVD was determined in a prospective cohort (the Cardiovascular Research and Rheumatoid Arthritis Study) of 353 outpatients with RA, and was compared with that in 1,852 population-based cohort study participants (155 had type 2 DM). We investigated fatal and nonfatal CVD (according to International Classification of Diseases, Ninth Revision criteria) and used Cox proportional hazards models to assess the incidence of CVD in RA, type 2 DM, and the general population. RESULTS: The 3-year incidence of CVD was 9.0% in patients with RA and 4.3% in the general population, corresponding with an incidence rate of 3.30 per 100 patient-years (95% confidence interval [95% CI] 2.08-4.25) and 1.51 per 100 person-years (95% CI 1.18-1.84), respectively. Compared with the general population, the age- and sex-adjusted hazard ratio (HR) for RA was 1.94 (95% CI 1.24-3.05, P = 0.004). Neither exclusion of patients with prior CVD at baseline nor adjustment for cardiovascular risk factors significantly influenced this. Compared with the nondiabetic population, nondiabetic patients with RA and those with type 2 DM had comparable HRs, 2.16 (95% CI 1.28-3.63, P = 0.004) and 2.04 (95% CI 1.12-3.67, P = 0.019), respectively. CONCLUSION: The risk of CVD in RA was significantly elevated compared with the general population, and comparable with the magnitude of risk in type 2 DM. | |
19128512 | The differential expressions of 78-kDa glucose-regulated protein of infiltrating plasma ce | 2009 Jan 9 | INTRODUCTION: The local production of pathogenic autoantibodies by plasma cells in synovium is one of the hallmarks of rheumatoid arthritis (RA). There may be a potential link between ectopic lymphoid neogenesis and the local autoimmunity in rheumatoid synovium. The unfolded protein response (UPR) has key roles in the development and maintenance of plasma cells secreting immunoglobulin. This study was designed to explore the potential links between the activation of the UPR of infiltrating plasma cells in inflamed peripheral joints and the histopathological variants of rheumatoid synovitis as well as the local production of pathogenic autoantibodies. METHODS: The variants of rheumatoid synovium were histopathologically classified into follicular and diffuse synovitis. Immunohistochemical and double-immunofluorescent stainings were performed to detect the expression of 78-kDa glucose-regulated protein (GRP78), a marker of activation of the UPR, in infiltrating plasma cells of synovium, and flow cytometry and immunoblotting analyses were performed to quantify GRP78 in plasma cells of synovial fluid in inflamed peripheral joints of RA. The detections were also taken in osteoarthritis (OA) as controls. The synovial fluid levels of anti-cyclic citrullinated peptide antibodies (anti-CCP) (IgG) were quantified with the enzyme-linked immunosorbent assay and corrected to those of total IgG in RA. RESULTS: Expressions of GRP78 were more intensive in infiltrating plasma cells in RA synovium relative to those in OA synovium (P < 0.001) and in synovium with follicular synovitis relative to that with diffuse synovitis (P < 0.001). Analyses by flow cytometry and immunoblotting showed that there was a significant upregulation of GRP78 of plasma cells from synovial fluid of RA compared with that of OA (P < 0.05) and from synovial fluid of follicular synovitis relative to that of diffuse synovitis (P < 0.05). Moreover, a positive relationship between the expression of GRP78 of plasma cells from synovial fluid and the corrected synovial levels of anti-CCP (IgG) was seen in RA (P < 0.001). CONCLUSIONS: There may be a link between enhanced activation of the UPR of plasma cells and ectopic lymphoid neogenesis as well as the local production of anti-CCP (IgG) in inflamed peripheral joints of RA. | |
19028128 | Regulatory T cells (Treg) in rheumatoid arthritis. | 2009 Jan | Modulation of the T-cell response depends chiefly on regulatory T cells (Treg), which express CD4 and CD25. Some Treg cells are present naturally, whereas others are induced in response to antigens. The immunomodulating effects of Treg cells are mediated by membrane molecules (e.g., CTLA4, GITR, and OX40) and cytokines. IL-35 seems to be a crucial mediator, although IL-10 and TGFbeta are also important. The role for Treg cells in rheumatoid arthritis (RA) has been established in both patients and animal models. Treg function is deficient in RA, whereas Treg counts vary. Treg counts increase in patients who are responding to TNFalpha antagonist therapy. Among current hypotheses, Treg expansion or transfer may hold promise for the treatment of RA. | |
20191516 | RAPID3 (Routine Assessment of Patient Index Data) on an MDHAQ (Multidimensional Health Ass | 2010 Feb | OBJECTIVE: To compare the Routine Assessment of Patient Index Data 3 (RAPID3) on a Multidimensional Health Assessment Questionnaire (MDHAQ) with the Disease Activity Score (DAS28), Clinical Disease Activity Index (CDAI), and individual core data set measures for correlations, agreement of activity levels, and time to score. METHODS: Four rheumatologists each assessed 50 patients with rheumatoid arthritis in "real-time" clinical care. Patients completed an MDHAQ. The rheumatologist then calculated RAPID3 (physical function, pain, patient global estimate), performed a 28-joint count, assigned a physician global estimate, and scored a CDAI, each timed by an observer. Erythrocyte sedimentation rate (ESR) was tested on the same date, and the DAS28-ESR was computed later, again timed by an observer. Spearman's rank-order correlations and comparisons of patients classified as high activity, moderate activity, low activity, and remission according to the DAS28, CDAI, and RAPID3 were computed and compared with kappa statistics. A second study of 25 "paper patients" was also performed to compare time to score the DAS28, CDAI, and RAPID3 on a 0-10 versus 0-30 scale. Mean and median times to score each index were computed. RESULTS: The 3 indices were correlated significantly, including agreement for >80% of patients for high/moderate activity. The mean time to perform a 28-joint count was 94 seconds, and the mean times to score the DAS28, CDAI, RAPID3 on a 0-10 scale, and RAPID3 on a 0-30 scale were 114, 106, 9.6, and 4.6 seconds, respectively. CONCLUSION: RAPID3 scores provide similar quantitative information to DAS28 and CDAI, while calculated on a 0-30 scale in about 5% of the time. | |
19896259 | [Pulmonary tuberculosis associated to adalimumab: a study of 3 cases]. | 2010 Apr | Tumour necrosis factor-alpha antagonist drugs represent a significant advance in the treatment of inflammatory diseases, such as rheumatoid arthritis, spondyloarthropathies, and intestinal inflammatory disease. The increase in tuberculosis with infliximab is known, but there is less data available that specifically associates tuberculosis with adalimumab. We present the cases of 2 patients with rheumatoid arthritis and one patient with ankylopoietic spondylitis on treatment with adalimumab, who developed pulmonary and disseminated tuberculosis despite following the screening and prophylaxis measures recommended in guidelines. We also review the association between treatment with tumour necrosis factor-alpha antagonists and tuberculosis. | |
19213744 | Cartilage proteoglycan aggrecan epitopes induce proinflammatory autoreactive T-cell respon | 2010 Jan | OBJECTIVES: To explore potential T-cell epitopes of the core protein of human cartilage proteoglycan aggrecan (PG) in patients with rheumatoid arthritis (RA) or osteoarthritis. METHODS: Peptide-specific T-cell proliferation and cytokine/chemokine production in response to PG-specific peptides were measured in RA and osteoarthritis patients and in healthy controls. RESULTS: Peptides representing amino acid regions 16-39 and 263-282 of PG were most frequently recognised by T cells in a subset of patients with RA or osteoarthritis. Peripheral blood mononuclear cells from these PG-reactive RA and osteoarthritis patients showed increased production of proinflammatory cytokines/chemokines in response to PG peptide stimulation. As PG p263-282 was found to show high sequence homology with Yersinia Yop protein, the corresponding bacterial (Yersinia) peptide was also tested. Remarkably, RA and osteoarthritis patients responding to the Yersinia peptide also responded to p263-282 of PG suggesting a possibility of molecular mimicry in these patients. CONCLUSIONS: These results indicate that PG-specific peptides, located in the G1 domain of PG, can induce (auto)antigenic T-cell responses in RA and osteoarthritis patients. These peptides might thus be involved in the immune pathogenesis and/or cartilage degradation in RA and osteoarthritis. | |
20201335 | [Assess of patients' functional condition with rheumatoid arthritis before and after physi | 2009 Nov | The aim of this study was to assess the impact of duration of disease and age on the functional condition of patients and also healing effectiveness in different duration of disease and age. MATERIAL AND METHODS: The study involved 31 patients with rheumatoid arthritis aged 40-70 years, with duration of disease 5-20 years. In this group was used following physical therapy technique: cryotherapy, ultrasound therapy, laser therapy, electrical stimulation TENS, iontophoresis, diadynamic and magnetic therapy. Before and after the treatment motor capacity was estimated using Health Assessment Questionnaire (HAQ). RESULTS: The presented results indicate improvement of measured parameters and increasement of patients independence after therapy, especially with duration of disease 5-10 years aged 60-70 years. CONCLUSIONS: Susceptibility of anti pain treatment using physical therapy increase with increasing duration of disease. Therapy influence on functional condition of patient decreasing with duration of disease. |