Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 19034456 | Protein tyrosine phosphatase gene C1858T allele confers risk for rheumatoid arthritis in H | 2009 May | The C1858T allele of the PTPN22 gene has been reported to confer risk for RA; but in some reports, the effect was restricted to RF- and/or anti-CCP-seropositive patients. Hungarian RA patients and matched controls were genotyped. The 1858T allele showed an increased prevalence in RA patients compared to controls. The 1858T allele represents a risk factor in the whole RA population (P = 0.001); an association was found both in RF-seropositive (P = 0.001) and anti-CCP-seropositive patients (P = 0.001), and in subjects with the combination of these factors (P = 0.002). In TT homozygotes, the estimated susceptibility to RA was more than double (OR = 5.04) of that seen in TC heterozygotes (OR = 1.89); the same gene dosage effect was observed in all seropositive RA subgroups. Our data show that the Hungarian RA patients belong to the populations in which the 1858T allele represents a susceptibility factor both in the RF- and/or anti-CCP-seropositive subjects, and the association exhibit a gene dosage dependency. | |
| 20020141 | Which is the dominant factor for perception of rheumatic pain: meteorology or psychology? | 2011 Mar | It is believed that there is an association between the weather and rheumatic symptoms. We aimed to investigate what kind of association is present and what are the factors which determine the nature of this association. Fifty-six subjects with rheumatic disease (31 RA, 15 SpA, 10 OA) who live in Antalya were followed between December 2005 and July 2006. Patients were asked to fill diaries which contain questions regarding the symptoms of their rheumatic diseases everyday. In every monthly visit, disease activity measurement, laboratory assessment and Beck depression inventory assessment were recorded. The symptomatic and psychological measurements were matched with the meteorological data of Antalya Regional Directorate of Meteorological Service of Turkish State. Correlation of symptoms with weather variables was investigated. Contributory effect of weather and of psychologic factors on symptom scores were evaluated by stepwise multiple regression analysis. Eighty-four percent of subjects belive in an association between weather and rheumatism, while 57% claimed to have ability to forecast weather. The maximum correlation coefficient between weather and arthritis symptoms was -0.451 and the maximum contribution of weather on symptoms was 17.1%. Arthritis symptoms were significantly contributed by Beck depression score. The belief about presence of weather-arthritis association was found to be stronger than its statistical power. Our results did not prove or rule out the presence of weather-rheumatism association. As long as the scientific attempts result in failure, the intuitive support in favour of the presence of weather-arthritis association will go on forever. | |
| 20306048 | Clonal expansions in selected TCR BV families of rheumatoid arthritis patients are reduced | 2011 Aug | Clonal expansions of autoreactive CD4+ T cells are frequently present in patients with rheumatoid arthritis (RA) and are stable over long periods of time. This study was undertaken to investigate the influence of anti-TNFα treatment on such clonal expansions in the peripheral CD4+ T-cell compartment. TNFα inhibiting therapies significantly reduced the total number of expanded clonotypes. This effect was mainly observed in clonal expansions in the BV6 family, while in clonal expansions of the BV14 family no such effect was seen. No change in the percentage of CD4+ CD28 null T cells was observed. Serum concentrations of the pro-homeostatic cytokine IL-7 were found to increase in patients responding TNFα-inhibiting therapy. These data argue for a normalization of adaptive immune mechanisms under TNFα inhibiting therapies, which may be secondary to the control of inflammation but contribute to the efficacy of cytokine blockade therapy. | |
| 20518837 | Genome-wide haplotype association analysis and gene prioritization identify CCL3 as a risk | 2010 Aug | Rheumatoid arthritis (RA) is a common autoimmune disease caused by a complex interaction of multiple genetic variants and environmental factors. The association between RA and genetic susceptibility loci has been observed in many different populations, and most studies have focused on univariate analyses of single nucleotide polymorphisms. We performed a genome-wide haplotype association study and prioritized RA-related genes within 100 kb in either direction of significant haplotypes (P < 0.0001), based on their similarity to known RA susceptibility genes. The results showed that the chemokine CCL3 was associated with susceptibility to RA. A haplotype that located CCL3 on chromosome 17q12 had significant correlation with RA (P = 7.56E-05), and the global similarity score of CCL3 was ranked in the top of all RA-related genes, excluding known susceptibility genes (P = 8.42E-07). Our findings provide further evidence for the potential importance of the chemokine CCL3 in RA, and will facilitate the further understanding of its role in immunological regulation and the pathogenesis of RA. | |
| 20470394 | Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and os | 2010 | INTRODUCTION: MicroRNAs (miRNAs), endogenous small noncoding RNAs regulating the activities of target mRNAs and cellular processes, are present in human plasma in a stable form. In this study, we investigated whether miRNAs are also stably present in synovial fluids and whether plasma and synovial fluid miRNAs could be biomarkers of rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: We measured concentrations of miR-16, miR-132, miR-146a, miR-155 and miR-223 in synovial fluid from patients with RA and OA, and those in plasma from RA, OA and healthy controls (HCs) by quantitative reverse transcription-polymerase chain reaction. Furthermore, miRNAs in the conditioned medium of synovial tissues, monolayer fibroblast-like synoviocytes, and mononuclear cells were examined. Correlations between miRNAs and biomarkers or disease activities of RA were statistically examined. RESULTS: Synovial fluid miRNAs were present and as stable as plasma miRNAs for storage at -20 degrees C and freeze-thawing from -20 degrees C to 4 degrees C. In RA and OA, synovial fluid concentrations of miR-16, miR-132, miR-146a, and miR-223 were significantly lower than their plasma concentrations, and there were no correlation between plasma and synovial fluid miRNAs. Interestingly, synovial tissues, fibroblast-like synoviocytes, and mononuclear cells secreted miRNAs in distinct patterns. The expression patterns of miRNAs in synovial fluid of OA were similar to miRNAs secreted by synovial tissues. Synovial fluid miRNAs of RA were likely to originate from synovial tissues and infiltrating cells. Plasma miR-132 of HC was significantly higher than that of RA or OA with high diagnosability. Synovial fluid concentrations of miR-16, miR-146a miR-155 and miR-223 of RA were significantly higher than those of OA. Plasma miRNAs or ratio of synovial fluid miRNAs to plasma miRNAs, including miR-16 and miR-146a, significantly correlated with tender joint counts and 28-joint Disease Activity Score. CONCLUSIONS: Plasma miRNAs had distinct patterns from synovial fluid miRNAs, which appeared to originate from synovial tissue. Plasma miR-132 well differentiated HCs from patients with RA or OA, while synovial fluid miRNAs differentiated RA and OA. Furthermore, plasma miRNAs correlated with the disease activities of RA. Thus, synovial fluid and plasma miRNAs have potential as diagnostic biomarkers for RA and OA and as a tool for the analysis of their pathogenesis. | |
| 20025759 | Use of supplementary phenotype to identify additional rheumatoid arthritis loci in a linka | 2009 Dec 21 | BACKGROUND: Although rheumatoid arthritis has been shown to have moderately strong genetic component, both linked loci identified in linkage analyses and susceptibility variants from association studies are short of adequately accounting for a comprehensive catalogue of the molecular factors underlying this complex disease. The objective of this study was to use supplementary phenotype based on cumulative hazard of rheumatoid arthritis to identify linkage evidence for new and additional rheumatoid arthritis loci in a genome-wide linkage analysis of 342 affected sibling pair families from the United Kingdom. METHODS: Using proportional hazards model, we estimated cumulative hazard of rheumatoid arthritis and then used it as a quantitative trait in a non-parametric multipoint variance component linkage analysis with 353 microsatellite markers distributed across the 22 autosomal chromosomes. RESULTS: We identified 3 new loci with genome-wide suggestive linkage evidence for rheumatoid arthritis on 9q21.13, 15p11.1 and 20q13.33. Our results also confirmed previously reported linkage evidence in the HLA-DRB1 region on chromosome 6 and on locus 1q32.1. CONCLUSION: This study demonstrates the potential for information gain through the use of supplementary phenotypes in genetic study of complex diseases to identify new and additional potential linked loci that are not detected by linkage analysis of traditional phenotypes; and our results provide further evidence of the involvement of multiple loci in the genetic aetiology of rheumatoid arthritis. | |
| 19074177 | Evaluation of different methods used to assess disease activity in rheumatoid arthritis: a | 2009 Apr | OBJECTIVES: To evaluate different methods of reporting response to treatment or disease status for their ability to discriminate between active therapy and placebo, or to reflect structural progression or patient satisfaction with treatment using an exploratory analysis of the Abatacept in Inadequate Responders to Methotrexate (AIM) trial. METHODS: 424 active (abatacept approximately 10 mg/kg) and 214 placebo-treated patients with rheumatoid arthritis (RA) were evaluated. METHOD: of reporting included: (1) response (American College of Rheumatology (ACR) criteria) versus state (disease activity score in 28 joints (DAS28) criteria); (2) stringency (ACR20 vs 50 vs 70; moderate disease activity state (MDAS; DAS28 <5.1) vs low disease activity state (LDAS; DAS28 |
|
| 19208610 | The influence of sex on patients with rheumatoid arthritis in a large observational cohort | 2009 Mar | OBJECTIVE: To compare the sex differences of various components of rheumatoid arthritis (RA). METHODS: Data of 4823 patients from a large observational cohort study were analyzed. Remarkable differences were noted between the sexes, and overall, women had significantly higher disease activity. RESULTS: When variables were adjusted using sex, age, and duration, Health Assessment Questionnaire, rather than Disease Activity Score, contributed most to sex difference. Further analysis showed evidence that progression of disability was approximately 3 times more rapid in female patients compared to male patients. CONCLUSION: Women overall have higher RA disease activity and are prone to greater and faster progression of disability over time. | |
| 20202903 | Pharmacology of glucocorticoids in rheumatoid arthritis. | 2010 Jun | Glucocorticoids (GCs) provide one of the most effective treatments for rheumatoid arthritis (RA); however, their long-term use is marred by undesired side effects. Increased understanding of the mechanisms of glucocorticoid action enables the development of novel drugs, such as SEGRAs or liposomal glucococorticoids, trying to improve their benefit/risk ratio. But also trying to optimise the use of conventional glucocorticoids is a sensible approach. One example is a new modified release prednisone tablet formulation that has been recently shown to be clinically and significantly better than the conventional immediate-release preparation with respect to reducing morning stiffness of the joints. The 'old spear' can also be sharpened by collecting clear-cut evidence on the efficacy and safety of conventional glucocorticoid therapy and deriving from that reliable evidence-based recommendations. This short review summarises the current knowledge in this regard, with particular emphasis on recently published articles. | |
| 20016907 | [Deficits of routine occupational therapy services in rheumatic diseases: results of the R | 2010 Jul | The purpose of the present study is to describe the frequency and potential determinants of occupational therapy routine services in patients with rheumatic diseases. The study is based on a secondary analysis of the RheumaDat database. The results of the survey on 907 patients were analyzed regarding frequency of occupational therapy routine services and related sociodemographic and disease-specific variables. Approximately 8% of the study population received occupational therapy, patients with rheumatoid arthritis representing the largest proportion of these at 13%. Only patients with osteoarthritis showed a clear treatment pattern. Patients from this group receiving occupational therapy were older, had a longer duration of disease and were more affected. No clear appraisal of the therapy status in the rheumatoid arthritis or fibromyalgia group could be made. The results indicate shortages and the lack of a clear system in occupational therapy routine services in patients with different rheumatic diseases. | |
| 19734293 | Etanercept improves inflammation-associated arterial stiffness in rheumatoid arthritis. | 2009 Nov | OBJECTIVES: Increased arterial stiffness, an independent risk factor for premature coronary artery disease, has been reported in patients with RA. The objectives of this study were first to assess, in patients with RA, the relationship between disease activity, inflammation and augmentation index, which is a combined measure of arterial stiffness and pulse wave reflection. The second objective was to establish any effect anti-rheumatic treatment may have on augmentation index. METHODS: One hundred and forty-eight RA patients with no previous history of cardiovascular disease (CVD) had their augmentation index corrected for a heart rate of 75 beats per minute (AIx@75), and parameters of RA disease activity and CV risk measured. Forty-seven patients were then treated with either MTX (n = 21) or etanercept (ETAN) (n = 26), and assessments were repeated at 2 and 4 months. RESULTS: Patients with high CRP (> 10 mg/l) showed significantly higher mean AIx@75 than those with low CRP (< or = 10 mg/l) (33 +/- 8 vs 30 +/- 8%; P = 0.033). On regression analysis, log(10) CRP (beta = 0.298; P = 0.002), gender (beta = 0.257; P = 0.007), BMI (beta = -0.292; P = 0.004), diastolic blood pressure (beta = 0.260; P = 0.009) and age (beta = 0.194; P = 0.046) were independently associated with AIx@75. Treatment with ETAN (35 +/- 9, 32.5 +/- 1 and 32.5 +/- 8%; P = 0.025) but not MTX (31 +/- 1, 31 +/- 1 and 31 +/- 1%; P = 0.971) attenuated the AIx@75 significantly from baseline to Visits 2 and 3. CONCLUSIONS: Systemic inflammation (CRP) is an independent predictor of arterial stiffness and pulse wave reflection in patients with RA. ETAN but not MTX therapy reduces arterial stiffness and pulse wave reflection and may thus improve CV morbidity in RA. | |
| 19565483 | Pan-DR-binding Hsp60 self epitopes induce an interleukin-10-mediated immune response in rh | 2009 Jul | OBJECTIVE: Human Hsp60 is expressed in the joints of patients with rheumatoid arthritis (RA) and can elicit a regulatory T cell response in the peripheral blood and synovial fluid. However, Hsp60 can also trigger strong proinflammatory pathways. Thus, to understand the nature of these Hsp60-directed responses in RA, it is necessary to study such responses at the molecular, epitope-specific level. This study was undertaken to characterize the disease specificity and function of pan-DR-binding Hsp60-derived epitopes as possible modulators of autoimmune inflammation in RA. METHODS: Lymphocyte proliferation assays (using (3)H-thymidine incorporation and carboxyfluorescein diacetate succinimidyl ester [CFSE] staining) and measurement of cytokine production (using multiplex immunoassay and intracellular staining) were performed after in vitro activation of peripheral blood mononuclear cells from patients with RA, compared with healthy controls. RESULTS: A disease (RA)-specific immune recognition, characterized by T cell proliferation as well as increased production of tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), and IL-10, was found for 3 of the 8 selected peptides in patients with RA as compared with healthy controls (P < 0.05). Intracellular cytokine staining and CFSE labeling showed that CD4+ T cells were the subset primarily responsible for both the T cell proliferation and the cytokine production in RA. Interestingly, the human peptides had a remarkably different phenotype, with a 5-10-fold higher IL-10:TNFalpha ratio, compared with that of the microbial peptides. CONCLUSION: These results suggest a disease-specific immune-modulatory role of epitope-specific T cells in the inflammatory processes of RA. Therefore, these pan-DR-binding epitopes could be used as a tool to study the autoreactive T cell response in RA and might be suitable candidates for use in immunotherapy. | |
| 20068404 | Ofatumumab. | 2009 Jul | Ofatumumab is an anti-CD20 IgG1kappa human monoclonal antibody that is being considered by the US Food and Drug Administration and the European Medicines Agency for marketing approval as a treatment for chronic lymphocytic leukemia. The mAb is also being studied as a treatment for lymphoma, rheumatoid arthritis and multiple sclerosis. The candidate targets the same antigen as rituximab, but ofatumumab binds a novel, membrane-proximal epitope, and dissociates from its target at a slower rate compared to rituximab. Ofatumumab might be approved in the US by August 2009. | |
| 20056091 | [Relationship between the level of MCP-1 expression in sera of RA patients and ILD]. | 2010 Jan | AIM: To investigate the function and clinical significance of monocyte chemoattractant protein-1 MCP-1 in the pathogenesis of rheumatoid arthritis(RA)and the relation ship between the expression of MCP-1 in serum and interstitial lung disease (ILD) secondary from RA. METHODS: 60 patients with RA were divided into two groups: 30 cases with simple RA group and 30 cases with ILD secondary from RA (RA+ILD group). The control group incuided 20 healthy cases. Enzyme linked immunosorbent assay (ELISA ) was used to determine the serum expression of MCP-1 in patients healthy controls. The differences of MCP-1 level and other laboratory indexes (IgG, IgA, IgM, alpha2-G, gamma-G, RF, ESR, CRP, and the number of arthrocele) in different groups were compared with software spss13.0. RESULTS: The expression of MCP-1 in simple RA patients was significantly higher than that in the control group (P>0.05) and significantly lower than that in the RA+ILD group (P>0.01). The level of MCP-1 in serum of RA patieuts was positively correlated with IgG, IgM, and gamma-G. CONCLUSION: MCP-1 plays an important role in the pathogenesis of RA and may contribute to the promotion of lung fibrosis in ILD secondary from RA. | |
| 21044433 | Optimal administration and dosage of methotrexate. | 2010 Sep | Methotrexate (MTX) has been used for the treatment of rheumatic diseases, especially rheumatoid arthritis (RA), for some decades now. Although it had been known from pharmacokinetic studies for quite some time already that the bioavailability of MTX is superior when administered parenterally rather than orally, this had never been formally proven to be clinically relevant. In a recent randomised clinical trial, the two ways of administration have been directly compared. The fact that the patient group that received MTX s.c. had better clinical outcome than the oral group can be considered as proof that this hypothesis has now been confirmed. Although this result does not mean that every patient will be in need of parenteral administration of MTX, it suggests that very active patients and those with a worse prognosis may have more benefit from this strategy. | |
| 20380588 | Structural, cellular, and molecular evaluation of bone erosion in experimental models of r | 2010 Dec | Bone erosion is a clinical endpoint for various diseases including rheumatoid arthritis. In this paper, we used rodent arthritis models with severe bone erosion to examine the structural, cellular, and molecular aspects of the inflammation-driven bone resorption process. Our data show that bone loss is observed only in chronically, severely inflamed joints. The most severely affected anatomic sites were the metatarsal phalangeal joint and tarsal bones of the paw. The magnitude of the inflammation-driven bone erosion was dependent on both the duration of inflammatory response and the severity of the joint swelling response. The application of micro-computed tomography well demonstrated the therapeutic benefit of anti-IL-17A in protection of bones from erosion. Alterations in the cellular profile of the joint occurred prior to any major structural deterioration of the bone. Receptor activator for nuclear factor κB ligand, a potent inducer of osteoclast differentiation and bone resorption, was elevated in animals coincident with severe arthritis initiation. The experimental approaches and concepts outlined in this paper provide a valuable process to evaluate and quantify therapies that modulate rodent arthritis-associated bone-erosion models. | |
| 19337286 | Periodontitis in systemic rheumatic diseases. | 2009 Apr | Periodontitis is a chronic inflammatory disease that is characterized by loss of the periodontal ligament and alveolar bone, and is a major cause of tooth loss. Results from clinical and epidemiologic studies have suggested that periodontitis and tooth loss are more prevalent in individuals with rheumatoid arthritis (RA). However, the strength and temporality of the association are uncertain. Several biologically plausible causal and noncausal mechanisms might account for this association between periodontitis and RA. There is evidence to suggest that periodontitis could indeed be a causal factor in the initiation and maintenance of the autoimmune inflammatory response that occurs in RA. If proven, chronic periodontitis might represent an important modifiable risk factor for RA. In addition, patients with RA might show an increased risk of developing periodontitis and tooth loss through various mechanisms. Moreover, exposure to common genetic, environmental or behavioral factors might contribute to a noncausal association between both conditions. | |
| 19772834 | Intracellular signal pathways: potential for therapies. | 2009 Oct | Drawbacks to current therapies for rheumatoid arthritis and the high cost of many of these drugs have lead to the investigation of novel approaches for treatment of this disease. One such tactic is the targeting of proteins involved in intracellular signal transduction. Inhibitors of p38 kinase have largely failed in clinical trials, due to both lack of efficacy and adverse events. The degree of adverse events may reflect off-target effects or, conversely, may be a mechanism-related event subsequent to successful inhibition of p38. Drugs targeting Janus kinases or spleen tyrosine kinase have shown greater success in clinical trials. A thorough analysis of specificity, as well as publication of both positive and negative results, must be the goal of continuing trials of these and other inhibitors of signal transduction molecules. The success of many clinical trials in this novel class of drugs provides optimism that more cost-effective and improved therapies will soon be available. | |
| 20015375 | Immunoglobulin G galactosylation and sialylation are associated with pregnancy-induced imp | 2009 | INTRODUCTION: Improvement of rheumatoid arthritis (RA) during pregnancy has been causatively associated with increased galactosylation of immunoglobulin G (IgG) N-glycans. Since previous studies were small, did not include the postpartum flare and did not study sialylation, these issues were addressed in the present study. METHODS: Serum from 148 RA cases and 32 healthy controls was collected at several time points before, during and after pregnancy. Improvement during pregnancy and postpartum flare were determined according to the European League Against Rheumatism (EULAR) response criteria. Galactosylation and sialylation of Immunoglobulin G (IgG) and the presence of bisecting N-acetylglucosamine (GlcNAc) were analyzed by matrix-assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS). RESULTS: IgG1 and IgG2 galactosylation of the cases and controls increased during pregnancy with a maximum in the third trimester. Galactosylation decreased directly postpartum. IgG galactosylation of controls was at a higher level than cases (P < 0.001 at all time points) and a similar pattern was observed for sialylation. Moreover, there was a good association between galactosylation and sialylation. The increase in galactosylation was significantly more pronounced for cases with improvement than cases without improvement during pregnancy. The reverse was true for deteriorators and non-deteriorators postpartum. The presence of bisecting GlcNAc was not significantly influenced by pregnancy or postpartum for cases and controls. CONCLUSIONS: This large cohort study demonstrates the association of changes in galactosylation with both pregnancy-induced improvement and postpartum flare in RA-patients, suggesting a role for changes in glycosylation in the pregnancy-induced improvement of RA. | |
| 19040313 | Proposed metrics for the determination of rheumatoid arthritis outcome and treatment succe | 2009 Jan | OBJECTIVE: Patients with rheumatoid arthritis (RA) and their physicians often disagree as to the success of RA treatment or RA outcomes. However, guidelines (such as EULAR criteria for DAS scores) are heavily weighted toward joint counts and laboratory tests, and no guidelines exist for patient reported outcomes. Our aims were (1) to provide a patient-based definition of successful RA outcome or of treatment success and failure; (2) to describe the characteristics of patients meeting this definition; (3) to describe how external states such as disability and comorbidity influence definitions of health outcome; and (4) to derive surrogate-measure cutpoints for the definition. METHODS: A total of 20,268 patients with RA (5132 without comorbidity) were studied by recursive partitioning and regression methods to determine best dividing points between RA treatment and outcome success and non-success using 0-10 visual analog scales (VAS) for patient global assessment, pain, fatigue, and RA activity, and a Health Assessment Questionnaire (HAQ) scale. RESULTS: 14.5% of all patients and 22.9% of those without comorbidity were very satisfied with their health (success). Patient global at a level |