A5033400134- Rheumatoid Arthritis Research and Therapies
- Systemic Lupus Erythematosus Research
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Chronic Lymphocytic Leukemia Research
- Cytokine Signaling Pathways and Interactions
- Lymphoma Diagnosis and Treatment
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- Cancer-related Molecular Pathways
- Autoimmune and Inflammatory Disorders Research
- Mesenchymal stem cell research
- Osteoarthritis Treatment and Mechanisms
- Epigenetics and DNA Methylation
- Hepatitis C virus research
- Cell Adhesion Molecules Research
- Spondyloarthritis Studies and Treatments
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- Genetics and Neurodevelopmental Disorders
- Cancer Cells and Metastasis
- Viral Infections and Immunology Research
- Bone and Joint Diseases
- Musculoskeletal synovial abnormalities and treatments
- Fibromyalgia and Chronic Fatigue Syndrome Research
University of Leeds
2015-2024
NIHR Leeds Musculoskeletal Biomedical Research Unit
2015-2024
Leeds Teaching Hospitals NHS Trust
2013-2024
Chapel Allerton Hospital
2012-2021
St James's University Hospital
2002-2018
Institute of Rheumatology
2017
Laboratoire d'Informatique, de Robotique et de Microélectronique de Montpellier
2017
Wellcome Trust
2014-2015
Institute of Molecular Medicine
2013
University of Sheffield
2008
Real-time PCR is increasingly being adopted for RNA quantification and genetic analysis. At present the most popular real-time assay based on hybridisation of a dual-labelled probe to product, development signal by loss fluorescence quenching as degrades probe. Though this so-called 'TaqMan' approach has proved easy optimise in practice, probes are relatively expensive.We have designed new SYBR-Green I binding that quick, reliable, easily optimised compares well with published assay. Here we...
Our aim was to test the hypothesis that there is a deficit in CD4+CD25high regulatory T-cell population early rheumatoid arthritis (RA), either size or functional activity.Peripheral blood mononuclear cells were examined from subjects with active RA who had received no previous disease-modifying therapy (n = 43), individuals self-limiting reactive 14), stable, well-controlled 82) and healthy controls 72). The frequencies of T-cells quantified using flow cytometry, function assessed by...
Rituximab appears to be effective in many studies of systemic lupus erythematosus (SLE), with variable initial clinical response and time relapse. However, results a randomized controlled trial rituximab were negative. This study was undertaken evaluate the effectiveness SLE, using highly sensitive flow cytometry (HSFC), which can define B cell numbers 50-100 times lower than conventional techniques predicts responses rheumatoid arthritis.Thirty-nine patients active SLE started on standard...
Abstract Background: To study the biology of rare bone marrow (BM) multipotent mesenchymal stromal cells (MSCs), recognized protocols are needed. Colony‐forming unit‐fibroblast (CFU‐F) assays have historically been used for enumeration MSCs. However, need to isolate and further analyze MSCs requires new strategies based on cell surface markers. The purpose this work was verify phenotype BM in vivo develop flow cytometry‐based methods their evaluation. Methods: Pre‐enrichment with...
Combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockade has increased remission rates in patients rheumatoid arthritis. However, there are no guidelines regarding cessation of therapy. There is a need for markers predictive sustained following TNF blocker therapy.Patients (DAS28 <2.6) treated MTX as initial or delayed were recruited. Joints assessed grey scale synovitis power Doppler (PD) activity. Immunological assessment involved advanced six-colour flow...
Abstract Objective Controversy surrounds the identity and functionality of rare bone marrow–derived multipotential stromal cells (BM‐MSCs), including their differentiation capabilities, relationship to pericytes hematopoiesis‐supporting cells, relevance culture‐expanded progeny in studies skeletal biology development cell‐based therapies. The aim this study was clarify nature candidate BM‐MSCs by profiling transcripts that reflect different aspects putative functions vivo. Methods Rare,...
In patients with osteoarthritis (OA), bone marrow lesions (BMLs) are intimately linked to disease progression. We hypothesized that aberrant multipotential stromal cell (also known as mesenchymal stem [MSC]) responses within tissue contributes BML pathophysiology. The aim of this study was investigate and non-BML native subchondral MSCs for numeric, topographic, in vitro functional, gene expression differences.Ex vivo 3T magnetic resonance imaging (MRI) the femoral heads 20 hip OA performed....
We analyzed the status of retinoblastoma and p53 genes in 10 human hepatoma cell lines. Polyclonal anti-peptide antibodies generated against peptides homologous to COOH-terminal leucine-zipper domains protein allowed us identify two lines (Hep 3B FOCUS) with abnormal expression. The same have both lacked In contrast gene, expression gene was six additional Indeed, only Hep G2 hepatoblastoma line (and its derivative G2/2215) appeared normal Our studies indicate that abnormalities are common...
A proportion of patients with rheumatoid arthritis (RA) have disease that fails to respond an initial cycle rituximab. Using highly sensitive flow cytometry (HSFC), it has been shown most who do not exhibit a response, as measured using the European League Against Rheumatism (EULAR) criteria, persistent circulating B cell levels at week 2 after treatment This study was undertaken examine whether additional rituximab would improve depletion and clinical response in whose did cycle.Patients RA...
Achieving joint regeneration in rheumatoid arthritis (RA) represents a future challenge. Autologous synovial mesenchymal stem cells (MSCs) could be therapeutically exploited. However, the inflammatory milieu RA synovium adversely affect endogenous MSC function. To test this hypothesis, frequency and multipotency of MSCs was evaluated relation to existing inflammation.Synovial inflammation measured using arthroscopic visual analogue score (VAS) further validated immunohistochemistry flow...
Uncultured mesenchymal stromal cells (MSCs) are increasingly used in therapies; however, the effects of donor age on their biological characteristics and gene expression remain unclear. The aim this study was to investigate age-related changes bone marrow (BM) MSCs following minimal or no culture manipulation. Iliac crest BM aspirated from 67 healthy donors (19-89 years old) directly for colony-forming unit-fibroblast (CFU-F) assay CD45lowCD271+ cell enumeration. colonies were analysed...
Background: Inflammatory arthritis (IA) is an immune-related condition defined by the presence of clinical synovitis. Its most common form rheumatoid arthritis. Objective: To develop scores for predicting IA in at-risk persons using multidimensional biomarkers. Design: Prospective observational cohort study. Setting: Single-center, Leeds, United Kingdom. Participants: Persons with new musculoskeletal symptoms, a positive test result anticitrullinated protein antibodies, and no synovitis...
Type II collagen (CII) posttranslationally modified by reactive oxygen species (ROS-CII) that are present in the inflamed joint is an autoantigen rheumatoid arthritis (RA). The aim of this study was to investigate potential use anti-ROS-CII autoantibodies as a biomarker RA.CII exposed oxidants joint. Autoreactivity ROS-CII assessed enzyme-linked immunosorbent assays synovial fluid (SF) and serum samples obtained from patients during various phases RA. This group included disease-modifying...
X-box binding protein 1 (XBP1) is a central regulator of the endoplasmic reticulum (ER) stress response. It induced via activation IRE1 sensor as part unfolded response (UPR) and has been implicated in several diseases processes. XBP1 can also be activated direct to Toll-like receptor (TLR) ligation independently UPR but pathogenic significance this mode not well understood. Here we show that TLR-dependent operative synovial fibroblasts (SF) patients with active rheumatoid arthritis (RA). We...
Anticitrullinated protein antibody (ACPA)+ individuals with non-specific musculoskeletal symptoms are at risk of inflammatory arthritis (IA). This study aims to demonstrate the predictive value T cell subset quantification for progression towards IA and compare it previously identified clinical predictors progression.103 ACPA+ without synovitis were observed 3-monthly 12 months then as clinically indicated. The end point was development IA. Naïve, regulatory cells (Treg) inflammation related...