A5035173394- Chronic Lymphocytic Leukemia Research
- Complement system in diseases
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Lymphoma Diagnosis and Treatment
- Psoriasis: Treatment and Pathogenesis
- Immune Response and Inflammation
- Spondyloarthritis Studies and Treatments
- Virus-based gene therapy research
- Blood groups and transfusion
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- Immunodeficiency and Autoimmune Disorders
- Platelet Disorders and Treatments
- Autoimmune and Inflammatory Disorders Research
- Herpesvirus Infections and Treatments
- IL-33, ST2, and ILC Pathways
- Reproductive System and Pregnancy
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Viral-associated cancers and disorders
- Renal Diseases and Glomerulopathies
- Heparin-Induced Thrombocytopenia and Thrombosis
- CAR-T cell therapy research
Leeds Teaching Hospitals NHS Trust
2014-2025
University of Leeds
2012-2025
University of California, Los Angeles
2024
St James's University Hospital
2012-2022
NIHR Leeds Musculoskeletal Biomedical Research Unit
2020
International Society for Experimental Hematology
2019
Stellenbosch University
1991-2017
Wellcome Trust
2013
Institute of Molecular Medicine
2011
University of Liverpool
1997-2003
Dupilumab, an IL-4/IL-13 receptor blocker, has been linked to emergent seronegative inflammatory arthritis and psoriasis that form part of the spondyloarthropathy spectrum. We systematically investigated patterns immune disorders, including predominantly T helper 17‒(spondyloarthropathy pattern) 2‒mediated disorders humoral autoimmune pattern diseases, using VigiBase, World Health Organization's global pharmacovigilance adverse drug reactions. Several bioinformatics databases repositories...
Objectives Murine models of interleukin (IL)-23-driven spondyloarthritis (SpA) have demonstrated entheseal accumulation γδT-cells which were responsible for the majority local IL-17A production. However, IL-23 blockers are ineffective in axial inflammation man. This study investigated γδT-cell subsets normal human enthesis to explore biology IL-23/17 axis. Methods Human spinous processes soft tissue (EST) and peri-entheseal bone (PEB) harvested during elective orthopaedic procedures....
The human enthesis conventional T cells are poorly characterised.To study the biology of in enthesis.CD4+ and CD8+ were investigated 25 samples using immunofluorescence, cytometrically, bulk RNAseq quantitative real-time PCR following anti-CD3/CD28 bead stimulation to determine interleukin (IL)-17A tumour necrosis factor (TNF) levels. T-cell receptor (TCR) repertoires characterised a search for putative reactivity was carried out TCR3 database. impact pharmacological antagonism with retinoic...
Plasma cells (PCs), the terminal effectors of humoral immunity, are short-lived unless supported by niche environments in which they may persist for years. No model system has linked B cell activation with function to allow vitro generation long-lived PCs. Thus, full trajectory differentiation yet be investigated vitro. In this article, we describe a robust polyclonal human PCs from peripheral blood cells. After proliferative plasmablast phase, absence division, viability limited only...
Abstract Objectives A retrospective population‐based study to determine the incidence and prevalence of patients with rare blood disease paroxysmal nocturnal haemoglobinuria (PNH). Methods All were identified by flow cytometric detection cells deficient in glycosylphosphatidylinositol (GPI) linked proteins at a single diagnostic reference laboratory that serves Yorkshire based, Haematological Malignancy Research Network (HMRN) population 3.8 million. Results One hundred ninety‐seven...
Abstract Improving the chances of curing patients with cancer who have had surgery to remove metastatic sites disease is a priority area for research. Pexa-Vec (Pexastimogene Devacirepvec; JX-594, TG6006) principally immunotherapeutic oncolytic virus that has reached late-phase clinical trials. We report results single-center, nonrandomized biological end point study (trial registration: EudraCT number 2012-000704-15), which builds on success presurgical intravenous delivery viruses tumors....
Antimicrobial proteins influence intestinal microbial ecology and limit proliferation of pathogens, yet the regulation their expression has only been partially elucidated. Here, we have identified a putative pathway involving epithelial cells intraepithelial lymphocytes (iIELs) that leads to antimicrobial protein (AMP) production by Paneth cells. Mice lacking γδ iIELs (TCRδ-/-) express significantly reduced levels AMP angiogenin 4 (Ang4). These mice were also unable up-regulate Ang4...
Abstract Long-lived human plasma cells (PCs) play central roles in immunity and autoimmunity are enriched among the subpopulation of CD19neg PCs. However, whether PCs necessarily aged that have gradually lost CD19 expression is not known. Assessing peripheral blood samples at steady-state during acute response to influenza vaccination healthy donors, we identify presence phenotypic plasmablasts, proliferative precursor state mature PCs, demonstrate by ELISPOT these Ab-secreting (ASCs)....
Objective The importance of interleukin‐17A (IL‐17A) in the pathogenesis axial spondyloarthritis (SpA) has been demonstrated by success IL‐17A blockade. However, nature cell populations that produce this important proinflammatory cytokine remains poorly defined. We undertook study to characterize major IL‐17A–producing blood peripheral patients with SpA, a focus on mucosal‐associated invariant T (MAIT) cells, population known be capable producing IL‐17. Methods evaluated production from 5...
Objectives To assess antibody and T cell responses to SARS-CoV-2 vaccination in patients with rheumatoid arthritis (RA) on disease-modifying antirheumatic drugs (DMARDs). Methods This prospective study recruited 100 RA a variety of DMARDs for analysis, pre-vaccination 4 weeks post-vaccination. Positive response was defined as sera IgG binding ≥1 antigen. Those that remained seronegative after first were retested second vaccination; if still three. A an ELISpot count ≥7 interferon...
The interleukin-2-deficient (IL-2(-/-)) mouse model of ulcerative colitis was used to test the hypothesis that colonic epithelial cells (CEC) directly respond bacterial antigens and alterations in Toll-like receptor (TLR)-mediated signaling may occur during development colitis. TLR expression activation TLR-mediated pathways primary CEC healthy animals compared with IL-2(-/-) mice In animals, expressed functional TLR, response TLR4 ligand LPS, proliferated secreted cytokines IL-6 monocyte...
Although gammadelta T cells play a role in protecting tissues from pathogen-elicited damage to bacterial, viral and parasitic pathogens, the mechanisms involved protection have not been clearly elucidated. This has addressed using murine model of listeriosis, which mice lacking (TCRdelta(-/-)) is characterised by severe extensive immune-mediated hepatic necrosis. We show that these lesions are caused Listeria-elicited CD8(+) secreting high levels TNF-alpha accumulate liver Listeria-infected...
Objective To assess the prevalence of MYD 88 L265P mutation and variants within NLRP 3 evaluate status oligoclonal hematopoiesis in 30 patients with Schnitzler syndrome (SchS). Methods Thirty SchS were recruited from clinical centers. Six known acquired cryopyrin‐associated periodic syndromes ( aCAPS ) included as controls. Allele‐specific oligonucleotide–polymerase chain reaction was used for detection variant, next‐generation sequencing applied to analyze 28 genes associated...
Inflammatory mediators including chemokines play a critical role in acute pancreatitis. The precise nature of early inflammatory signals within the pancreas remains, however, unclear. We examined ability isolated pancreatic acini to synthesize CC chemokine monocyte chemotactic protein-1 (MCP-1) and CXC cytokine-induced neutrophil chemoattractant (CINC) response secretagogue cerulein at physiological supraphysiological concentrations. Isolated rat maintained short-term (≤48 h) primary culture...
Although gammadelta T cells are involved in the response to many pathogens, dynamics and heterogeneity of local cell remains poorly defined. We recently identified as regulators macrophages dendritic during resolution Streptococcus pneumoniae-mediated lung inflammation. Here, using PCR, spectratype analysis flow cytometry, we show that multiple subsets, including those bearing Vgamma1, Vgamma4 Vgamma6 TCR, increase number lungs infected mice, but not associated lymphoid tissue. These...
<h3>Objective.</h3> Since Wegener’s granulomatosis (WG) represents a relapsing disease, efforts have been made to reliably predict relapses using blood tests. Followup measures such as conventionally determined C-reactive protein (CRP), antineutrophil cytoplasmic antibody (C-ANCA) titer, and proteinase-3 (PR3) ELISA are applied. We evaluated whether during remission elevated highly sensitive CRP (hsCRP) precedes relapse marker of subclinical inflammation thus might improve clinical...
Abstract γδ T cells play important but poorly defined roles in pathogen-induced immune responses and preventing chronic inflammation pathology. A major obstacle to defining their function is establishing the degree of functional redundancy heterogeneity among cells. Using mice deficient Vγ1+ which are a component cell response microbial infection, specific immunoregulatory role for macrophage homeostasis during infection has been established. By contrast, no significant pathogen containment...