A5014494732- Renal Diseases and Glomerulopathies
- Vasculitis and related conditions
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- T-cell and B-cell Immunology
- Systemic Lupus Erythematosus Research
- Immunodeficiency and Autoimmune Disorders
- Sarcoidosis and Beryllium Toxicity Research
- Cell Adhesion Molecules Research
- Dialysis and Renal Disease Management
- Dietary Effects on Health
- Systemic Sclerosis and Related Diseases
- Urticaria and Related Conditions
- Regulation of Appetite and Obesity
- Phagocytosis and Immune Regulation
- Otitis Media and Relapsing Polychondritis
- Immune cells in cancer
- Salivary Gland Disorders and Functions
- Inflammatory Bowel Disease
- Complement system in diseases
- IgG4-Related and Inflammatory Diseases
- Cell death mechanisms and regulation
- Biosimilars and Bioanalytical Methods
Age UK
2019-2023
GlaxoSmithKline (United Kingdom)
2017-2020
GlaxoSmithKline (India)
2020
Hammersmith Hospital
2008-2018
Imperial College London
2003-2017
Imperial College Healthcare NHS Trust
2010-2015
University College London
2006-2014
The Royal Free Hospital
2011
Chang Gung Memorial Hospital
2006
Charing Cross Hospital
2006
Anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis with renal involvement requires treatment potentially toxic drugs to reduce morbidity and mortality, there is a major challenge determine clinical histological features predictive of prognosis. The aim our study was evaluate the use 2010 international classification for ANCA-associated glomerulonephritis (AAGN) as predictor outcome when used in conjunction other prognostic factors. One hundred four patients AAGN treated at...
Background and objectives: Encapsulating peritoneal sclerosis (EPS) is a severe fibrotic reaction in patients on long-term dialysis (PD). The early clinical features may be nonspecific. purpose of the study to assess reliability diagnostic utility abdominal CT scanning diagnosis EPS. Design, setting, participants, & measurements: Abdominopelvic scans 27 diagnosed with EPS radiologic grounds our unit from 1997 2006 were retrospectively analyzed. In addition, 35 control scored: 15 hemodialysis...
Immunosuppressant drugs reduce proteinuria and anti-phospholipase A2 receptor autoantibodies (PLA2R-Ab) in primary membranous nephropathy (PMN) with varying success associated toxicities. This study aimed to evaluate the effect of belimumab on PLA2R-Ab participants PMN.In this prospective, open-label, experimental medicine study, 14 PMN persistent nephrotic-range received up 2 years monotherapy (10 mg/kg, every 4 weeks). Changes (urinary protein:creatinine ratio), PLA2R-Ab, albumin,...
Rituximab (RTX) has been shown to be effective as an induction agent in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), but studies have limited by short-term follow-up. We decided investigate the long-term efficacy and safety of RTX-based cyclophosphamide (CYP)-sparing regimen (CycLowVas) for renal AAV.Consecutive patients with AAV presenting de novo or a major relapse, except those serum creatinine >500 μmol/L, previous treatment RTX pulmonary haemorrhage cerebral...
The involvement of IL-1beta and other pro-inflammatory cytokines in most forms glomerulonephritis is now well established. P2X(7) receptor, an ATP-sensitive P2X functions not only as a non-selective cation channel, but it also involved the rapid processing release IL-1beta, apoptosis necrotic cell death. Therefore, we wanted to investigate if expression this receptor altered glomeruli rodent models glomerulonephritis.P2X(7) protein was investigated using immunohistochemistry, assessed TUNEL...
Induction therapy with oral cyclophosphamide (CYP) has been a mainstay of treatment in patients severe renal failure secondary to ANCA-associated vasculitis (AAV). Recent evidence proposes using pulsed intravenous CYP less disease minimize adverse events. It is unclear if this can be translated those dialysis-dependent insufficiency.All AAV presenting between 2005 and 2010 requiring dialysis at presentation were retrospectively analyzed. Patients treated plasma exchange, corticosteroids,...
GSK3050002, a humanized IgG1κ antibody with high binding affinity to human CCL20, was administered in first-in-human study evaluate safety, pharmacokinetics (PK) and pharmacodynamics (PD). An experimental skin suction blister model employed assess target engagement the ability of compound inhibit recruitment inflammatory CCR6 expressing cells.This randomized, double-blind (sponsor open), placebo-controlled, single-centre, single ascending intravenous dose escalation trial 48 healthy male...
Lymphocyte activation gene [LAG]-3 is an immune checkpoint and its expression identifies recently activated lymphocytes that may contribute to inflammation. We investigated the role of LAG-3 by analysing function in cells from blood tissue patients with ulcerative colitis [UC].The phenotypic properties LAG-3+ T were determined flow cytometry, qRT-PCR single-cell RNA-sequencing. quantified correlated disease activity. The functional effects tested using a depleting anti-LAG-3 monoclonal...
Objectives. B cell depletion is an effective treatment strategy in ANCA-associated vasculitis (AAV). Ofatumumab a fully humanized anti-CD20 mAb that has shown efficacy the of haematological malignancy and RA. The use ofatumumab AAV not previously been reported. Methods. This study was based on case series eight patients who received ofatumumab, conjunction with low-dose CYC oral steroids, AAV. Results. Eight ofatumumab: seven for remission induction active disease (three relapsing; four new...
We previously validated a scoring system for abdominal/pelvic CT scans in patients with symptomatic encapsulating peritoneal sclerosis (EPS). of EPS were significantly different from control dialysis (PD) or haemodialysis patient scans; performed before was clinically evident near normal 9 13 patients. have now investigated scanning as screening modality larger group on long-term PD.Pre-diagnostic 20 routine other indications at least 3 months developed, and later diagnostic when evident,...
Activated T cells drive a range of immune‐mediated inflammatory diseases. LAG‐3 is transiently expressed on recently activated CD4 + and CD8 cells. We describe the engineering first‐in‐human clinical study (NCT02195349) GSK2831781 (an afucosylated humanized IgG1 monoclonal antibody enhanced with high affinity for Fc receptors antibody‐dependent cellular cytotoxicity capabilities), which depletes expressing was tested in phase I/Ib, double‐blind, placebo‐controlled study, randomized 40...
Summary Monocyte subsets with differing functional properties have been defined by their expression of CD14 and CD16. We investigated these in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) determined surface ANCA autoantigens. Flow cytometry was performed on blood from 14 patients active AAV, 46 AAV remission 21 controls. The proportion classical (CD14highCD16neg/low), intermediate (CD14highCD16high) non-classical (CD14lowCD16high) monocytes levels CD16 were...
Eur J Clin Invest 2010; 40 (12): 1067–1073 Abstract Background Peritoneal fibrosis manifests clinically as membrane failure or encapsulating peritoneal sclerosis (EPS). There are no clinical biochemical tests to determine the rate of progression fibrosis. CCL18/pulmonary and activation‐regulated chemokine (PARC) is profibrotic stimulates collagen production independent effect transforming growth factor beta. This has not been studied in dialysis (PD) patients. Materials methods We have...
Genetic investigation of crescentic glomerulonephritis (Crgn) susceptibility in the Wistar Kyoto rat, a strain uniquely susceptible to nephrotoxic nephritis (NTN), allowed us positionally clone activator protein-1 transcription factor Jund as gene associated with Crgn. To study influence deficiency (Jund(-/-)) on immune-mediated renal disease, accelerated NTN was examined Jund(-/-) mice and C57BL/6 wild-type (WT) controls. showed exacerbated glomerular crescent formation macrophage...
FcγRIIb is the sole inhibitory FcR for IgG in humans and mice, where it involved negative regulation of Ab production cellular activation. FcγRIIb-deficient mice show exacerbated disease following induction nephrotoxic nephritis (NTN). In this study, we determined origin FcγRIIb-knockout phenotype by inducing NTN with a deficiency on either B cells alone (FcγRIIB(fl/fl)/CD19Cre(+)) or myeloid (FcγRIIB(fl/fl)/CEBPαCre(+)). Deletion from did not increase susceptibility to NTN, compared...
Objective. Necrotizing and crescentic GN usually presents with rapidly declining renal function, often in association multisystem autoimmune disease, a poor outcome if left untreated. We aimed to describe the features of patients who have presented these histopathological findings but minimal disturbance function.