Soluble syndecan-3 binds chemokines, reduces leukocyte migration in vitro and ameliorates disease severity in models of rheumatoid arthritis.

Background: Syndecans are heparan sulfate proteoglycans that occur in membrane-bound or soluble forms. Syndecan-3, the least well-characterised of the syndecan family, is highly expressed on synovial endothelial cells in rheumatoid arthritis patients. Here, it binds pro-inflammatory chemokines with evidence for a role in chemokine presentation and leukocyte trafficking into the joint, promoting the inflammatory response.

Inflammatory biomarkers do not distinguish between patients with sciatica and referred leg pain within a primary care population: results from a nested study within the ATLAS cohort.

Background: There is increasing interest in the role of pro-inflammatory cytokines in the pathogenesis of sciatica and whether these could be potential targets for treatment. We sought to investigate serum biomarker levels in patients with low back-related leg pain, including sciatica.

Methods: Primary care consulters aged > 18 with low back-related leg pain were recruited to a cohort study (ATLAS).

Anti-citrullinated protein antibody positive rheumatoid arthritis is primarily determined by rheumatoid factor titre and the shared epitope rather than smoking per se.

Objective: To analyse the relationship between rheumatoid factor (RF) titre, smoking and HLA-DRB1 alleles coding a "shared epitope" (SE) in relation to anti-citrullinated protein antibody (ACPA) positivity in rheumatoid arthritis (RA).

Methods: RA patients (n = 658) attending rheumatology clinics in Cornwall, UK (cohort 1) were stratified according to RF and ACPA titre, and smoking pack years at diagnosis. A further 409 RA patients from North Staffordshire, UK (cohort 2) were studied to confirm the relationship between RF levels, smoking and ACPA positivity in relation to SE status.

An initial investigation into endothelial CC chemokine expression in the human rheumatoid synovium.

Rheumatoid arthritis (RA) is a destructive and chronic autoimmune inflammatory disease. Synovial inflammation is a major feature of RA and is associated with leukocyte recruitment. Leukocytes cross the endothelial cells (ECs) into the synovial tissue and fluid and this migration is mediated via a range of chemokines and adhesion molecules on the ECs.

Clinical efficacy of oral alendronate in ankylosing spondylitis: a randomised placebo-controlled trial.

Objectives: A prospective, double blind, randomised, placebo controlled trial over 2 years was performed to test the efficacy of alendronate, an oral aminobisphosphonate, in improving symptoms and arrest disease progression in patients with mild to severe ankylosing spondylitis (AS).

Methods: 180 patients with AS were randomised to receive weekly alendronate 70 mg or placebo (1:1 randomisation). BAS-G was the primary outcome measure with Bath indices as secondary outcomes.

DNA methylation at diagnosis is associated with response to disease-modifying drugs in early rheumatoid arthritis.

Aim: A proof-of-concept study to explore whether DNA methylation at first diagnosis is associated with response to disease-modifying antirheumatic drugs (DMARDs) in patients with early rheumatoid arthritis (RA).

Patients & Methods: DNA methylation was quantified in T-lymphocytes from 46 treatment-naive patients using HumanMethylation450 BeadChips. Treatment response was determined in 6 months using the European League Against Rheumatism (EULAR) response criteria.

Genome-wide profiling in treatment-naive early rheumatoid arthritis reveals DNA methylome changes in T and B lymphocytes.

Aim: Although aberrant DNA methylation has been described in rheumatoid arthritis (RA), no studies have interrogated this epigenetic modification in early disease. Following recent investigations of T and B lymphocytes in established disease, we now characterize in these cell populations genome-wide DNA methylation in treatment-naive patients with early RA.

Patients & Methods: HumanMethylation450 BeadChips were used to examine genome-wide DNA methylation in lymphocyte populations from 23 early RA patients and 11 healthy individuals.

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.

The role of parvovirus B19 and the immune response in the pathogenesis of acute leukemia.

In this article, we review the evidence suggesting a possible role for B19 virus in the pathogenesis of a subset of cases of acute leukemia. Human parvovirus B19 infection may complicate the clinical course of patients with acute leukemia and may also precede the development of acute leukemia by up to 180 days. Parvovirus B19 targets erythroblasts in the bone marrow and may cause aplastic crisis in patients with shortened-red cell survival.

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.

Influence of adult height on rheumatoid arthritis: association with disease activity, impairment of joint function and overall disability.

Objectives: To investigate whether normal variation of adult height is associated with clinical characteristics in rheumatoid arthritis (RA), including disease activity (DAS28), impairment of joint function (mechanical joint score, MJS) and overall disability (health assessment questionnaire, HAQ).

Methods: A cohort (134 males, 287 females) of consecutively recruited RA patients of Northern European origin was studied. Height, weight and demographic information were obtained.

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.

Age at onset of rheumatoid arthritis: association with polymorphisms in the vascular endothelial growth factor A(VEGFA) gene and an intergenic locus between matrix metalloproteinase (MMP) 1 and 3 genes.

Objectives: The present paper aims to investigate whether polymorphisms in the vascular endothelial growth factor A (VEGFA) gene and the loci of matrix metalloproteinase (MMP) 1 and 3 genes are associated with age at onset of RA.

Methods: A sample of 413 hospital-based RA patients of Caucasian origin was studied. Common single-nucleotide polymorphisms (SNP) with likely importance were typed, including rs699947, rs833061, rs2010963 and rs3025039 in VEGFA, and rs1799750 in the MMP1 gene, rs3025058, rs679620 in the MMP3 gene and rs495366 located within the region between the MMP1 and MMP3 genes.

Association of cytokine and matrix metalloproteinase profiles with disease activity and function in ankylosing spondylitis.

Introduction: The pathology of ankylosing spondylitis (AS) suggests that certain cytokines and matrix metalloproteinases (MMPs) might provide useful markers of disease activity. Serum levels of some cytokines and MMPs have been found to be elevated in active disease, but there is a general lack of information about biomarker profiles in AS and how these are related to disease activity and function. The purpose of this study was to investigate whether clinical measures of disease activity and function in AS are associated with particular profiles of circulating cytokines and MMPs.

Hypoalbuminaemia, systemic albumin leak and endothelial dysfunction in peritoneal dialysis patients.

Background: Inflammation, hypoalbuminaemia and peritoneal protein clearance are important predictors of survival in patients treated with peritoneal dialysis (PD). We hypothesized that the common link is abnormal endothelial barrier function. To test this, we explored associations between hypoalbuminaemia, systemic albumin leak and soluble markers of systemic inflammation and endothelial injury.

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).

Relationship between smoking and patient-reported measures of disease outcome in ankylosing spondylitis.

Objective: To investigate the relationship between smoking and disease activity, pain, function, and quality of life in patients with ankylosing spondylitis (AS).

Methods: Patients with AS (n = 612) from areas across the United Kingdom took part in a cross-sectional postal survey. Patient-reported outcome measures including the Bath AS Disease Activity Index, the Bath AS Functional Index (BASFI), a numerical rating scale (NRS) of pain, the AS quality of life questionnaire (ASQoL), and the evaluation of AS quality of life measures (EASi-QoL) were analyzed in terms of smoking status and relationship with pack-year history.

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.

High-intensity interval training attenuates the exercise-induced increase in plasma IL-6 in response to acute exercise.

This aims of this study were to investigate the effects of carbohydrate availability during endurance training on the plasma interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha response to a subsequent acute bout of high-intensity interval exercise. Three groups of recreationally active males performed 6 weeks of high-intensity interval running. Groups 1 (LOW+GLU) and 2 (LOW+PLA) trained twice per day, 2 days per week, and consumed a 6.