DNA methylation profiling of synovial fluid FLS in rheumatoid arthritis reveals changes common with tissue-derived FLS.

Aim: Alterations in DNA methylation contribute to the abnormal phenotype of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). We profiled genome-wide DNA methylation in these cells from synovial fluid, a more readily accessible source of disease-associated cells.

Patients & Methods: Genome-wide DNA methylation was interrogated in fluid-derived FLS from five RA and six osteoarthritis patients using Human Methylation 450 Bead Chip and bisulfite pyrosequencing.

Genome-wide DNA methylation profiling in rheumatoid arthritis identifies disease-associated methylation changes that are distinct to individual T- and B-lymphocyte populations.

Changes to the DNA methylome have been described in patients with rheumatoid arthritis (RA). In previous work, we reported genome-wide methylation differences in T-lymphocyte and B-lymphocyte populations from healthy individuals. Now, using HumanMethylation450 BeadChips to interrogate genome-wide DNA methylation, we have determined disease-associated methylation changes in blood-derived T- and B-lymphocyte populations from 12 female patients with seropositive established RA, relative to 12 matched healthy individuals.

Epigenome-wide profiling identifies significant differences in DNA methylation between matched-pairs of T- and B-lymphocytes from healthy individuals.

Multiple reports now describe changes to the DNA methylome in rheumatoid arthritis and in many cases have analyzed methylation in mixed cell populations from whole blood. However, these approaches may preclude the identification of cell type-specific methylation, which may subsequently bias identification of disease-specific changes. To address this possibility, we conducted genome-wide DNA methylation profiling using HumanMethylation450 BeadChips to identify differences within matched pairs of T-lymphocytes and B-lymphocytes isolated from the peripheral blood of 10 healthy females.

Association of circulating levels of MMP-8 with mortality from respiratory disease in patients with rheumatoid arthritis.

Introduction: Matrix metalloproteinases (MMPs) are implicated in the destruction of the joint and have been shown to be strongly associated with inflammation in rheumatoid arthritis (RA). Circulating MMPs have also been associated with cardiovascular disease in the general population, and are predictive of cardiovascular mortality. The purpose of the present study was to determine whether circulating levels of MMPs are predictive of mortality in RA.

Interaction between smoking and functional polymorphism in the TGFB1 gene is associated with ischaemic heart disease and myocardial infarction in patients with rheumatoid arthritis: a cross-sectional study.

Introduction: Transforming growth factor-beta1 (TGF-beta1) is a pleiotropic cytokine that plays important roles in immunity and inflammation. Some studies have suggested that polymorphism in the TGFB1 gene is associated with heart disease in the general population. The purpose of the present study was to determine whether common single-nucleotide polymorphisms (SNP) in the TGFB1 gene are associated with ischaemic heart disease (IHD) and/or myocardial infarction (MI) in patients with rheumatoid arthritis (RA), and to investigate the influence of smoking on any association.

Polymorphism in the vascular endothelial growth factor A (VEGFA) gene is associated with serum VEGF-A level and disease activity in rheumatoid arthritis: differential effect of cigarette smoking.

Objective: To assess the impact of common genetic variants in the vascular endothelial growth factor A (VEGFA) gene on circulating VEGF-A levels and disease activity in patients with rheumatoid arthritis (RA).

Methods: A cohort (n=419) of consecutively recruited RA patients of Caucasian origin was studied. Disease activity (DAS28) was recorded on a regular basis (0, 12 and 24 months).

Interaction between smoking and polymorphism in the promoter region of the VEGFA gene is associated with ischemic heart disease and myocardial infarction in rheumatoid arthritis.

Objective: To determine whether variants in the vascular endothelial growth factor A (VEGFA) gene are associated with ischemic heart disease (IHD) and/or myocardial infarction (MI) in patients with rheumatoid arthritis (RA), and whether there is evidence of a gene-smoking interaction.

Methods: PCR-RFLP assays were used to determine the genotypes of VEGFA single-nucleotide polymorphisms (SNP) including VEGFA-2578A/C (rs699947), -460C/T (rs833061), +405C/G (rs2010963), and +936C/T (rs3025039) in 418 subjects with RA. Smoking history was obtained on each patient, and IHD and MI status was recorded.

Effect of psychological distress on continuation of anti-tumor necrosis factor therapy in patients with rheumatoid arthritis.

Objective: To investigate the relationship of psychological distress and associated factors with continuation of tumor necrosis factor (TNF) antagonist therapy in patients with rheumatoid arthritis (RA).

Methods: Patients about to start therapy with TNF antagonists (n = 166) were assessed for psychological distress using the Hospital Anxiety and Depression Scale (HADS). A core set of demographic and clinical variables, including comorbidities from medical records and cigarette smoking history by questionnaire, were recorded at baseline and regular intervals thereafter.

Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study.

Objective: To investigate the safety and efficacy of ofatumumab, a novel human anti-CD20 monoclonal antibody (mAb), in patients with active rheumatoid arthritis (RA) whose disease did not respond to > or = 1 disease-modifying antirheumatic drug.

Methods: This combined phase I/II study investigated the safety and efficacy of 3 doses of ofatumumab. In part A (phase I), 39 patients received 2 intravenous (i.

Relationship between pack-year history of smoking and response to tumor necrosis factor antagonists in patients with rheumatoid arthritis.

Objective: To determine whether there is a quantitative relationship between smoking history and response to therapy with tumor necrosis factor (TNF) antagonists.

Methods: A history of cigarette smoking was obtained from a questionnaire completed by each patient starting therapy with TNF antagonists since 2002 (n=154). A core set of demographic and clinical variables was recorded at baseline and at 3 and 12 months.

Circulating levels of tumor necrosis factor receptors are highly predictive of mortality in patients with rheumatoid arthritis.

Objective: To investigate whether circulating levels of soluble tumor necrosis factor receptors (sTNFR) are predictive of mortality in rheumatoid arthritis (RA).

Methods: Levels of sTNFRI and sTNFRII at study entry were quantified using enzyme-linked immunosorbent assays in sera from 401 white patients with RA followed up for 13 years. Patients were tracked via the National Health Service Central Register, and the relationship between sTNFR levels and mortality was analyzed using a Cox proportional hazards regression model.

Polymorphism in the tumour necrosis factor receptor II gene is associated with circulating levels of soluble tumour necrosis factor receptors in rheumatoid arthritis.

Levels of soluble tumour necrosis factor receptors (sTNFRs) are elevated in the circulation of patients with rheumatoid arthritis (RA). Although these receptors can act as natural inhibitors of tumour necrosis factor-alpha, levels of sTNFRs in RA appear to be insufficient to prevent tumour necrosis factor-alpha induced inflammation. The factors that regulate circulating levels of sTNFRs are unclear, but polymorphisms in the tumour necrosis factor receptor genes may play a role.

Anemia in rheumatoid arthritis: association with polymorphism in the tumor necrosis factor receptor I and II genes.

Objective: To investigate whether polymorphisms in the tumor necrosis factor receptor I (TNFRSF1A) and receptor II (TNFRSF1B) genes are associated with the anemia observed in rheumatoid arthritis (RA).

Methods: We studied a group of Caucasian patients (n = 160) with established RA on whom longitudinal data of hemoglobin (Hb) levels over 5 years were recorded. A second group of patients (n = 102) with early RA was used for a confirmation study.

Assessment of the 3-dimensional Fastrak measurement system in measuring range of motion in ankylosing spondylitis.

Objective: To assess the repeatability and validity of the electromagnetic 3-dimensional tracking system, Fastrak, in measuring cervical spine and shoulder movement in patients with ankylosing spondylitis (AS).

Methods: Fifty patients with AS had their cervical spine and shoulder movements measured on up to 3 occasions with the Fastrak. Patients also completed disease-specific and generic patient assessed health instruments, and their spinal mobility was assessed by tape measure methods.

Can gold therapy be used more safely in rheumatoid arthritis? Adverse drug reactions are more likely in patients with nodular disease, independent of HLA-DR3 status.

Objective: . To investigate whether features associated with severe rheumatoid arthritis (RA) are predictive of adverse drug reactions (ADR) to gold salts, independent of HLA-DR3 status.

Methods: A cohort of patients with RA (n = 41) who developed thrombocytopenia (platelets < 100 10(6)/l) or proteinuria (> 1.

Patient centered assessment of ankylosing spondylitis-specific health related quality of life: evaluation of the Patient Generated Index.

Objective: To evaluate the Patient Generated Index (PGI) for the measurement of individualized health related quality of life in ankylosing spondylitis (AS).

Methods: The PGI asks patients to nominate areas of their lives affected by their disease that they consider the most important. Semistructured interviews with AS patients produced a trigger list of areas of life affected by AS.

Nodular disease in rheumatoid arthritis: association with cigarette smoking and HLA-DRB1/TNF gene interaction.

Objective: To investigate the association of nodular disease in rheumatoid arthritis (RA) with smoking, seropositivity, and polymorphisms at HLA-DRB1 and TNF loci.

Methods: Consecutive patients with RA (n = 420) attending a hospital clinic were examined for the presence of subcutaneous nodules. Rheumatoid factor (RF) status and HLA-DRB1 genotype were determined on every patient, and their smoking history was recorded.

Relationship among the HLA-DRB1 shared epitope, smoking, and rheumatoid factor production in rheumatoid arthritis.

Objective: Rheumatoid factor (RF) production in rheumatoid arthritis (RA) is generally associated with more severe disease. In some studies, RF production has been associated with carriage of HLA-DRB1 alleles encoding the RA-associated shared epitope (SE). Patients who smoke are also more likely to be RF positive.

Smoking and disease severity in rheumatoid arthritis: association with polymorphism at the glutathione S-transferase M1 locus.

Objective: To determine whether the relationship between smoking and disease severity in women with rheumatoid arthritis (RA) is associated with polymorphism at the glutathione S-transferase (GST) M1 locus.

Methods: Genotyping for GSTM1 was carried out using polymerase chain reaction methodology on 164 women with established RA. Smoking history was obtained on each patient.