Browse

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

ID PMID Title PublicationDate abstract
21267739 [The indication for radiosynoviorthesis. From the perspective of the nuclear medicine expe 2011 Jan Radiosynovectomy or radiosynoviorthesis (RSO), the intra-articular injection of beta-emitting radionuclides (e.g. colloidal preparations of 90-Yttrium, 186-Rhenium or 169-Erbium), is an approved, reliable and easily performed therapy for the treatment of chronic synovitis without harmful side effects. The best clinical results have been obtained in patients with predominantly inflammatory joint disease such as rheumatoid arthritis or reactive arthritis. But RSO is also established to treat pain and persistent effusions after total knee replacement. It also represents an adjuvant therapy in patients with pigmented villonodular synovitis to protect against recurrence following synovectomy. In patients with hemophilia and arthropathy a reduction in joint bleeding is seen and the use of coagulation factor is reduced. The indication for RSO should be made in close cooperation between the referring physician, the rheumatologist and the nuclear medicine expert in the context of a multimodal therapy concept. In this way, success rates of over 80%, with only few side effects, can be achieved, particularly in rheumatoid arthritis, reactive arthritis and hemophilic arthropathy.
21073898 The role of Natural Killer cells in the pathogenesis of rheumatoid arthritis: major contri 2011 May Natural Killer (NK) cells are lymphocytes of the innate immune system, originally described by their capacity to control tumour cells and eliminate virus-infected cells. However accumulating evidence suggests that NK cells can interact with various components of the immune system and play a critical role in autoimmune diseases by limiting or exacerbating immune responses. Rheumatoid arthritis is a chronic inflammatory disease characterised by joint inflammation and cartilage and bone destruction. NK cells are enriched within the joints of patients with rheumatoid arthritis but how they contribute to disease pathology is currently not fully elucidated. This review will outline the current understanding of NK cell biology and how these cells may modulate disease pathogenesis in rheumatoid arthritis through interactions with other immune cells.
21913036 Correlation of protease-activated receptor-2 expression and synovitis in rheumatoid and os 2012 Oct Protease-activated receptor-2 (PAR-2) is known to be pro-inflammatory and increasing evidence points to an inflammatory component in osteoarthritis. This investigation examined the relationship between synovitis and PAR-2 expression, histological and immunohistochemical analysis being performed on synovial samples obtained from OA and RA patients, along with non-arthritic samples obtained by post mortem (PM). Samples were also analysed for PAR-4 expression, this receptor also having putative pro-inflammatory roles. Analysis involved comparison of inflammatory indices (synovial thickness and monocyte infiltration) with expression of PAR-2 and PAR-4. Synovial explants were also analysed for TNFα generation in the presence of a PAR-2 antagonist (ENMD-1068) or vehicle. OA synovia showed heterogeneity of inflammatory indicators, some samples overlapping with those from the RA cohort whilst others appeared similar to the PM cohort. PAR-2 expression, both in the lining layer and the interstitium, correlated strongly and significantly with synovial thickness (r = 0.91) and monocyte infiltration (r = 0.83), respectively (P < 0.001 in both cases), and this remains significant on individual cohort analysis. PAR-2 was co-localised to CD3 and CD68 cells in RA and OA synovium as well as fibroblasts derived from these synovia. PAR-4 was also expressed, but the relationship with inflammatory indicators was substantially weaker. Inflammatory indicators in OA synovia showed considerable variability, but correlated strongly with PAR-2 expression, suggesting PAR-2 upregulation in synovitis. Heterogeneity of inflammatory indicators was paralleled by wide variation in TNFα generation between samples. Secretion of this cytokine was dose-dependently inhibited by ENMD-1068, providing evidence of a functional role for PAR-2 in promoting synovitis.
22213280 Everyday life with rheumatoid arthritis and implications for patient education and clinica 2012 Mar OBJECTIVES: This study aimed to explore how everyday life is affected by rheumatoid arthritis (RA), in order to inform patient education and clinical practice and generate further research. METHODS: Six focus group interviews were conducted with, in total, 32 participants. Interview data were analysed using content analysis methods. RESULTS: The study showed that RA affected almost every aspect of participants' everyday lives, particularly self-identity, social relationships, work and relationships with health and social care professionals. A small number of the participants did not have these experiences, due to receiving fast diagnosis and effective medical treatment. CONCLUSION: The findings point to a need to increase knowledge about RA, support symptom management and reduce the physical, social and psychological challenges posed by RA in everyday life. An individualized and engaged approach to patient education, taking the individual experiences as the point of departure, is suggested. The results indicate directions for further research. The general implications for patient education that emerge from this study might not address the support needs of those who did not experience significant changes in everyday life. A more detailed and in-depth understanding about living with RA in the first years after diagnosis would provide a valuable supplement to the many retrospective studies, and useful knowledge in the design of patient education tailored to those who are newly diagnosed with RA.
21634436 Liposomal drug formulations in the treatment of rheumatoid arthritis. 2011 Aug 1 Liposomes have been extensively investigated as drug delivery systems in the treatment of rheumatoid arthritis (RA). Low bioavailability, high clearance rates and limited selectivity of several important drugs used for RA treatment require high and frequent dosing to achieve sufficient therapeutic efficacy. However, high doses also increase the risk for systemic side effects. The use of liposomes as drug carriers may increase the therapeutic index of these antirheumatic drugs. Liposomal physicochemical properties can be changed to optimize penetration through biological barriers and retention at the site of administration, and to prevent premature degradation and toxicity to nontarget tissues. Optimal liposomal properties depend on the administration route: large-sized liposomes show good retention upon local injection, small-sized liposomes are better suited to achieve passive targeting. PEGylation reduces the uptake of the liposomes by liver and spleen, and increases the circulation time, resulting in increased localization at the inflamed site due to the enhanced permeability and retention (EPR) effect. Additionally liposomal surfaces can be modified to achieve selective delivery of the encapsulated drug to specific target cells in RA. This review gives an overview of liposomal drug formulations studied in a preclinical setting as well as in clinical practice. It covers the use of liposomes for existing antirheumatic drugs as well as for new possible treatment strategies for RA. Both local administration of liposomal depot formulations and intravenous administration of passively and actively targeted liposomes are reviewed.
21523363 Lipid profile in Tunisian patients with rheumatoid arthritis. 2011 Oct This study aims to assess the prevalence of dyslipidaemia in Tunisian patients with active RA and to investigate the clinical and biological associated factors. A cross-sectional study was conducted on 92 unselected patients with active RA (77 females and 15 males, aged 49.1 ± 12.5 years) and 82 healthy subjects (68 females and 14 males, aged 50.8 ± 13.3 years). We recorded the patients' characteristics and the results of a lipid profile test (total cholesterol, TC; high-density lipoprotein cholesterol, HDL-c; low-density lipoprotein cholesterol, LDL-c; triglyceride, TG; lipoprotein (a), Lp (a); apolipoprotein A-1, apo A-1 and apolipoprotein B, apo B). In comparison to the control group, RA patients showed a higher prevalence of associated dyslipidaemia (95.7% versus 65.9% of cases, p < 0.001). Sera of patients showed higher TC (4.86 ± 1.07 versus 3.98 ± 0.73 mmol/L, p < 0.001), LDL-c (3.49 ± 0.98 versus 1.99 ± 0.62 mmol/L, p < 0.001), Lp (a) (288.04 ± 254.59 versus 187.94 ± 181.37 mmol/L, p = 0.004) and lower HDL-c (0.66 ± 0.24 versus 1.12 ± 0.3 mmol/L, p < 0.001). TC/HDL-c, LDL-c/HDL-c and non-HDL-c/HDL-c were also higher in RA patients; they were 8.24 ± 3.20 versus 3.76 ± 1.26 (p < 0.001), 5.91 ± 2.48 versus 1.92 ± 0.99 (p < 0.001) and 7.24 ± 3.20 versus 2.76 ± 1.26 (p < 0.001), respectively. Apo A-1 was correlated to Lp (a) (r = 0.291, p = 0.005). Corticoid dose was not associated to dyslipidaemia, but in multiple regression models, corticoid dose may be negatively related to some atherogenic markers, in particular non-HDL-c. Tunisian patients with markedly active RA experience substantially reduced serum HDL-c and increased TC, LDL-c and Lp (a) concentrations as well as increased TC/HDL-c, LDL-c/HDL-c and non-HDL-c/HDL-c ratios.
23244209 A decrease in galectin-1 (Gal-1) levels correlates with an increase in anti-Gal-1 antibodi 2013 BACKGROUND: Several studies have confirmed that galectin-1 (Gal-1) plays a role in controlling the immune response because of its pro-apoptotic effect. Although studies based on a rheumatoid arthritis (RA) mouse model have suggested a crucial role for Gal-1 in inflammation, clinical data are lacking. We have detected the presence of autoantibodies against galectins in blood, but their physiological meaning remains unknown. OBJECTIVES: To compare plasma and synovial levels of Gal-1 in RA patients and in healthy controls, and correlate them with clinical parameters. METHODS: Plasma and synovial (non-arthritic knee effusion) samples were collected from RA patients and healthy donors. All patients were receiving treatment with steroids and/or disease-modifying anti-rheumatic drugs (DMARDs). A blood sample was taken at a baseline visit to determine plasma anti-cyclic citrullinated peptide (anti-CCP) antibodies, tumour necrosis factor alpha (TNF-α), Gal-1, and anti-Gal-1 autoantibodies. RESULTS: Although plasma levels of Gal-1 were similar in patients and controls, the concentration of Gal-1 was significantly reduced in the synovial fluid of patients with RA. This reduction was not correlated with TNF-α or C-reactive protein (CRP) levels. However, the decrease in synovial Gal-1 correlated with a significant increase in anti-Gal-1 autoantibodies and anti-CCP antibody titres, suggesting a physiological effect of autoantibodies limiting the amount Gal-1 and potentially blocking its biological effect in RA patients. CONCLUSION: Gal-1 levels were significant reduced at the synovial level in RA patients, possibly as a consequence of the increase in anti-Gal-1 autoantibodies.
22898213 Current considerations for the management of musculoskeletal pain in Asian countries: a sp 2012 Aug Chronic pain is a complex problem that eludes precise definition and can be clinically difficult to diagnose and challenging to treat. In the Asia-Pacific region, prevalence estimates that chronic pain ranges from 12% to 45% of the population, with musculoskeletal, rheumatic or osteoarthritis pain making up the majority of the disease burden. Implementation of current management guidelines into routine clinical practice has been challenging and as a result, patients with musculoskeletal pain are often poorly managed. For these reasons, a multidisciplinary Chronic Pain Advisory Board of leading physicians from various Asian countries was convened to explore ways to improve treatment and compliance, especially among patients with osteoarthritis and rheumatoid arthritis. We have identified a number of unmet therapeutic needs and prioritized initiatives with the potential to contribute toward a more integrated approach to chronic pain management. Key priorities included using evidence-based interventions as recommended by current guidelines, particularly those aspects pertinent to addressing treatment priorities in Asia (e.g., patient compliance), and the incorporation of cyclooxygenase-2 inhibitors and non-steroid anti-inflammation drugs into the management algorithms for osteoarthritis and rheumatoid arthritis. Treatment must be individualized for each patient based on efficacy, side-effect profile and drug accessibility. Further studies are required to examine head-to-head comparisons among analgesics, combinations of analgesics and long-term efficacy outcomes. Our increasing understanding of the problem combined with the promise of new therapy options offers hope for improved management of musculoskeletal pain in Asian countries.
22695407 Relevance of the new pre-cachexia and cachexia definitions for patients with rheumatoid ar 2012 Dec BACKGROUND & AIMS: The recently proposed definitions of 'pre-cachexia' and 'cachexia' might offer new possibilities for the detection of malnutrition in patients with rheumatoid arthritis (RA). METHODS: The prevalence of different components of nutritional status and the compiled definitions of 'precachexia' and 'cachexia' were measured in a cohort of 103 patients with moderately active RA. Nutritional status was determined by measuring unintentional weight loss, BMI, and muscle strength. Bio-electrical Impedance Analysis (BIA) was used to determine fat free mass index (FFMI) and fat mass index. In addition, appetite, pain, fatigue, and inflammatory activity were assessed. The prevalence of 'pre-cachexia' and 'cachexia' was calculated from different combinations of these parameters. RESULTS: 20% of the study population had a low FFMI (<10th percentile), and 95% had a decreased muscle strength ( < lowest tertile). Weight loss and loss of appetite, both essential elements in the newly proposed (pre-)cachexia definitions, were uncommon. The prevalence of 'pre-cachexia' and 'cachexia' was both 1% (n = 1). CONCLUSIONS: In spite of altered body composition and impaired body function, the recently proposed definitions of both 'pre-cachexia' and 'cachexia' were unable to identify and diagnose impaired nutritional status in RA patients mainly because of low prevalences of weight loss and decreased appetite.
22466712 Anti-citrullinated peptide antibodies in the serum of heavy smokers without rheumatoid art 2012 Jul The objective of this study is to analyse the frequency and levels of anti-citrullinated peptide/protein antibodies (ACPA) in the serum of non-rheumatoid arthritis (RA) heavy smokers with and without chronic obstructive pulmonary disease (COPD) and compare them with healthy never smokers and patients with RA. Serum samples of 110 heavy smokers without RA, 209 healthy never smokers and 134 patients with RA were tested for ACPA using a commercial anti-cyclic citrullinated peptide antibodies (CCP2) test and a homemade chimeric fibrin/filaggrin citrullinated synthetic peptide (anti-CFFCP) ELISA test. The frequency of positive results and autoantibody levels were compared between groups. The prevalence of the two types of ACPA was slightly higher in heavy smokers than in never smokers, although the difference was not significant, and significantly lower than in RA patients. The highest prevalence of positive ACPA in heavy smokers was found in subjects with COPD (7.4% of positive anti-CFFCP in patients with COPD in comparison with 2.4% in never smokers: OR 3.26; 95% CI 0.85-12.6, p = 0.089). Mean serum levels of ACPA in heavy smokers were not significantly different from those of never smokers. Heavy smokers with COPD had significantly higher levels of anti-CFFCP than those without COPD, although almost all patients had serum levels below the cut-off values. The prevalence of ACPA in heavy smokers without RA is low, but seems to be higher in heavy smokers with COPD. Larger studies are necessary to confirm these findings and determine the relationship between ACPA and lung disease.
21345816 Monocyte migration to the synovium in rheumatoid arthritis patients treated with adalimuma 2011 Jun OBJECTIVES: The mechanism of action of treatment with tumour necrosis factor (TNF) blockers in rheumatoid arthritis (RA) is still not completely understood. The aim of this study was to test if adalimumab treatment could affect the influx of monocytes into the synovium. METHODS: A novel technique was used to analyse the migration of labelled autologous monocytes before and 14 days after initiation of adalimumab treatment using scintigraphy. CD14 monocytes were isolated from patients with RA, using a positive selection procedure with magnetic-activated cell sorting, and labelled with technetium-99m-hexamethylpropylene-amino-oxime. Scintigraphic scans were made 1, 2 and 3 h after re-infusion. RESULTS: As early as 14 days after the start of treatment with adalimumab a significant decrease in disease activity score evaluated in 28 joints was shown. There was no significant decrease in the influx of monocytes into the joint at this time. CONCLUSIONS: This study indicates that adalimumab treatment does not reduce the influx of monocytes into the synovium early after initiation of treatment. As previous studies showed a rapid decrease in macrophage infiltration after TNF-antibody therapy, which could not be explained by increased cell death, this points to an important role for enhanced efflux of inflammatory cells from the synovium.
20440528 Serological investigation of IgG levels and subclasses in rheumatoid arthritis patients fo 2011 Feb The purpose of this study was to investigate whether clinical improvement in patient with rheumatoid arthritis (RA) taking oral Bovine type II collagen (bCII) is associated with changes in levels of anti-bCII total IgG antibody and its subclasses. Four groups were given either 5, 0.5 or 0.05 mg of bCII or a placebo in a double-blind randomised control trial. The sera IgG anti-collagen type II and antibodies of the IgG subclasses, IgG1-4, were measured at the start and end of the trial by ELISA. Total IgG anti-collagen II antibodies in the pooled active treatment groups were statistically significantly reduced compared with the placebo group (p = 0.021). Decreasing total IgG titres were observed in the 0.5-mg group (p = 0.008), 0.05-mg group (p = 0.004) and 5-mg group (p = 0.078) before and after treatment. For IgG1, IgG2, IgG3 and IgG4 subclasses, in the 0.5-mg group in which the best clinical response was observed, there was statistically significant decreases observed in the IgG2 and IgG3 subclasses (p = 0.047, p = 0.046). Treatment with bCII in patients with RA led to a reduction in anti-collagen II antibody titre indicating an active biological effect as observed previously in animal model of RA. The largest decrease in total and subclasses of anti-collagen antibody titres occurred in the groups of patients with the best therapeutic response to bCII, supporting the conclusion of the clinical trial and suggests that immune regulation explains the therapeutic effect.
20349066 Patterns of preventive health services in rheumatoid arthritis patients compared to a prim 2011 Sep To determine the proportion of rheumatoid arthritis (RA) patients receiving preventive health care according to US Preventive Services Task Force recommendations compared with a community-based population sample, with emphasis on dyslipidemia testing, given the increased risk of cardiovascular disease (CVD) in RA patients. Patients with RA (ICD-9 code 714.0 at ≥2 office visits with a rheumatologist) and a primary care physician (PCP) at the Geisinger Health System (GHS) were identified through electronic health records. The records were searched back from 3/31/08 for the length of time required to satisfy each outcome measure. Percentages were compared with population testing rates using the Pearson Chi-square test. Eight hundred and thirty-one RA patients were compared to 169,476 subjects with a PCP at GHS, stratified by gender and age. Patients with RA were more likely to have had dyslipidemia and osteoporosis testing compared with the general population (86 vs. 75 and 75 vs. 55%, respectively, P < 0.0001 for both). The proportion of RA patients receiving breast and cervical cancer testing was similar to the general population. The majority (79%) of lipid testing was ordered by PCPs. Those RA patients with recommended lipid testing had more traditional CVD factors (hypertension, diabetes, coronary artery disease). RA patients are screened more than the general population for two RA-related co-morbidities, i.e. dyslipidemia and osteoporosis. The RA patients with traditional cardiovascular risk factors are more likely to be tested for dyslipidemia. Further work is warranted to improve testing for modifiable CVD risk factors in this group with multiple co-morbidities.
21452312 Venous and arterial thromboembolic events in adalimumab-treated patients with antiadalimum 2011 Apr OBJECTIVE: We observed 3 patients who developed severe venous and arterial thromboembolic events during treatment with adalimumab, 2 of whom had rheumatoid arthritis (RA) and 1 of whom had psoriatic arthritis. Antiadalimumab antibodies were detected in all 3 patients. We undertook this study to determine whether the development of antiadalimumab antibodies was associated with thromboembolic events during adalimumab treatment. METHODS: A retrospective search (with blinding with regard to antiadalimumab antibody status) for thromboembolic events was performed in a prospective cohort of 272 consecutively included adalimumab-treated RA patients. Incidence rates were calculated and hazard ratios (HRs) were estimated using Cox regression. None of the index patients were part of the cohort. RESULTS: Antiadalimumab antibodies were detected in 76 of 272 patients (28%). Eight thromboembolic events were found, 4 of which had occurred in patients with antiadalimumab antibodies. The incidence rate was 26.9/1,000 person-years for patients with antiadalimumab antibodies and 8.4/1,000 person-years for patients without those antibodies (HR 3.8 [95% confidence interval 0.9-15.3], P = 0.064). After adjustment for duration of followup, age, body mass index, erythrocyte sedimentation rate, and prior thromboembolic events, the HR was 7.6 (95% confidence interval 1.3-45.1) (P = 0.025). CONCLUSION: These findings suggest that the occurrence of venous and arterial thromboembolic events during adalimumab treatment is higher in patients with antiadalimumab antibodies than in those without antiadalimumab antibodies. Patient numbers were relatively small; therefore, validation in other cohorts is mandatory.
22820516 FRAX updates 2012. 2012 Sep PURPOSE OF REVIEW: There is an increasing recognition that the management of osteoporosis requires the characterization of fracture risk to be based on absolute risk rather than single measures such as bone mineral density (BMD). FRAX, the most widely used tool that incorporates clinical risk factors with or without BMD, was launched in 2008. This brief review addresses the development of FRAX since then and describes some of the issues that continue to be discussed as FRAX plays an increasing role in clinical practice. RECENT FINDINGS: FRAX is a platform technology that will continue to develop. High-quality updated epidemiology of fracture and mortality can lead to recalibration of models. The addition of new risk factors is complex as the process requires validation in an international setting as well as a comprehensive assessment of how such new factors interact with the existing FRAX variables. Nonetheless, clinical interpretation can be enhanced by taking into account the potential adjustments of FRAX probabilities and several of these are described. SUMMARY: FRAX is being incorporated in an increasing number of clinical guidelines, and assessment and intervention thresholds have been provided to instruct clinical decision-making. There is an increasing body of evidence that patients deemed at highest risk of fracture by FRAX, with or without the use of BMD, will overlap significantly with those identified by previous guidelines and will respond to appropriate osteoporosis therapy.
22307942 Safety and efficacy of ocrelizumab in combination with methotrexate in MTX-naive subjects 2012 Aug OBJECTIVE: To determine the efficacy and safety of ocrelizumab (OCR) with methotrexate (MTX) in MTX-naive rheumatoid arthritis (RA) patients. METHODS: In a randomised, double-blind, controlled trial, patients received placebo+MTX (MTX; n=210), OCR 200 mg×2+MTX (OCR 200; n=200) or OCR 500 mg×2+MTX (OCR 500; n=203). OCR/placebo (two intravenous infusions) was given on days 1 and 15, with fixed re-treatment scheduled at weeks 24/26, 52/54 and 76/78. Due to early termination of OCR dosing, there was no formal primary end point analysis (change from baseline in modified total Sharp score (ΔmTSS) at week 104). Analyses are reported for week 52 outcomes. RESULTS: At week 52, treatment with OCR+MTX compared with MTX alone reduced progression of joint damage (mean (SD) change in ΔmTSS: OCR 200, 0.66 (4.51); OCR 500, 0.27 (2.91); MTX alone, 1.59 (4.82); p=0.001 and p=0.003, respectively vs MTX alone) and improved clinical signs and symptoms (American College of Rheumatology 20 response: OCR 200, 73.0%; OCR 500, 71.0%; MTX alone, 57.5%; p<0.005 for each OCR vs MTX alone). Serious infection rates per 100 patient-years were similar with OCR 200 and MTX alone (2.6 (95% CI 0.9 to 6.1) and 3.0 (1.1 to 6.5), respectively), but higher with OCR 500 (7.1 (3.9 to 11.9)). CONCLUSIONS: OCR 200 mg and 500 mg with MTX in MTX-naive patients with RA were effective in inhibiting joint damage progression and improving RA signs and symptoms. OCR 500 mg with MTX was associated with an increased rate of serious infections.
23250099 Infliximab reduces cardiac output in rheumatoid arthritis patients without heart failure. 2012 Nov OBJECTIVE: Human anti-tumor necrosis factor (TNF-α) monoclonal antibody (infliximab) is used to treat autoimmune diseases such as rheumatoid arthritis (RA). Although the risk of worsening heart failure has been described in patients under chronic treatment, the acute cardiovascular effects of this drug are unknown in RA patients without heart failure. METHODS: 14 RA patients with normal echocardiography and no history of heart failure were evaluated during the 2-hour infliximab (3-5 mg/kg) infusion period, using a noninvasive hemodynamic beat-to-beat system (Portapres). Stroke volume (SV); systolic, diastolic and mean blood pressures (SBP, DBP and MBP, respectively); cardiac output (CO); heart rate (HR); and total peripheral vascular resistance (PVR) were recorded. All patients also received saline infusion instead of infliximab as a control. Significant differences in hemodynamic parameters were determined using Tuckey's test. All values were expressed as mean ± standard deviation (SD). RESULTS: Fourteen RA patients (6M/8F) with mean age of 47.2 ± 8.8 years were evaluated. A significant decrease was found in cardiac output and stroke volume (7.04 ± 2.3 to 6.12 ± 2.1 l/min and 91 ± 29.0 to 83 ± 28.8 mL/beat, respectively) after infliximab infusion. Although not statistically significant, a progressive increase was detected in SBP, DBP and total PVR during infusion. Saline infusion did not cause significant hemodynamic changes in the same group of RA patients. No adverse effects were observed during the infusion period. CONCLUSION: Acute infliximab administration decreased cardiac output due to low stroke volume in RA patients without heart disease. The results also demonstrated that, in spite of its negative inotropic effect, infliximab enhanced BP, probably by increasing PVR.
22682473 Batch correction of microarray data substantially improves the identification of genes dif 2012 Jun 8 BACKGROUND: Batch effects due to sample preparation or array variation (type, charge, and/or platform) may influence the results of microarray experiments and thus mask and/or confound true biological differences. Of the published approaches for batch correction, the algorithm "Combating Batch Effects When Combining Batches of Gene Expression Microarray Data" (ComBat) appears to be most suitable for small sample sizes and multiple batches. METHODS: Synovial fibroblasts (SFB; purity > 98%) were obtained from rheumatoid arthritis (RA) and osteoarthritis (OA) patients (n = 6 each) and stimulated with TNF-α or TGF-β1 for 0, 1, 2, 4, or 12 hours. Gene expression was analyzed using Affymetrix Human Genome U133 Plus 2.0 chips, an alternative chip definition file, and normalization by Robust Multi-Array Analysis (RMA). Data were batch-corrected for different acquiry dates using ComBat and the efficacy of the correction was validated using hierarchical clustering. RESULTS: In contrast to the hierarchical clustering dendrogram before batch correction, in which RA and OA patients clustered randomly, batch correction led to a clear separation of RA and OA. Strikingly, this applied not only to the 0 hour time point (i.e., before stimulation with TNF-α/TGF-β1), but also to all time points following stimulation except for the late 12 hour time point. Batch-corrected data then allowed the identification of differentially expressed genes discriminating between RA and OA. Batch correction only marginally modified the original data, as demonstrated by preservation of the main Gene Ontology (GO) categories of interest, and by minimally changed mean expression levels (maximal change 4.087%) or variances for all genes of interest. Eight genes from the GO category "extracellular matrix structural constituent" (5 different collagens, biglycan, and tubulointerstitial nephritis antigen-like 1) were differentially expressed between RA and OA (RA > OA), both constitutively at time point 0, and at all time points following stimulation with either TNF-α or TGF-β1. CONCLUSION: Batch correction appears to be an extremely valuable tool to eliminate non-biological batch effects, and allows the identification of genes discriminating between different joint diseases. RA-SFB show an upregulated expression of extracellular matrix components, both constitutively following isolation from the synovial membrane and upon stimulation with disease-relevant cytokines or growth factors, suggesting an "imprinted" alteration of their phenotype.
21181275 Association study of single nucleotide polymorphisms in pre-miRNA and rheumatoid arthritis 2011 Nov The aim of this study was to perform an association study between two single nucleotide polymorphisms (SNPs) rs2910164 G>C and rs3746444 T>C in pre-miRNA (hsa-mir-146a and hsa-mir-499) and rheumatoid arthritis (RA) in the Han Chinese population. 208 Han Chinese patients with RA and 240 healthy controls were recruited in this study. The SNPs was genotyped by polymerase chain reaction-restriction fragment length polymorphism. Anti-cyclic citrullinated peptide (anti-CCP) antibody was measured by enzyme linked immunosorbent assay and rheumatoid factor (RF) was measured by rate nephelometry. The genotype frequencies between cases and controls were compared by χ(2) analysis. No significant association between the SNPs (rs2910164 and rs3746444) and RA was observed (P = 0.631 and 0.775, respectively), and the SNPs did not show any association with the RF-positive (P = 0.631 and 0.775, respectively). However, there was a significant difference on the level of anti-CCP antibody between different genotypes in rs3746444 (P = 0.007). The heterozygote CT had significantly higher level of anti-CCP antibody compared with homozygote CC and TT (P = 0.054 and 0.003, respectively). We first investigated the association between the SNPs (rs2910164 G>C and rs3746444 T>C) in the pre-miRNA (hsa-mir-146a and hsa-mir-499) and RA in a Han Chinese population. We did not find a significant association between the SNPs and the susceptibility to RA, while the SNP rs3746444 may affect anti-CCP antibody production.
21871363 Arthroscopic synovectomy of the wrist. 2011 Aug Arthroscopic synovectomy is safe and reliable, with mild postoperative morbidity. The rationale of a surgical synovectomy is to excise inflamed synovium and thereby, remove as much effusion and inflammatory substrate as possible. In most cases, arthroscopic synovectomy is performed as an outpatient procedure. The technique has also been used for other diagnoses causing wrist arthritis, but very few results have been reported and the indications remain to be defined. In rheumatoid arthritis (RA), juvenile chronic arthritis (JCA), systemic lupus erythematosus (SLE), and postinfectious monoarthritis, a long period of increased comfort and improved function can be anticipated.