A5005037626- Vasculitis and related conditions
- Renal Diseases and Glomerulopathies
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- T-cell and B-cell Immunology
- Cell Adhesion Molecules Research
- Sarcoidosis and Beryllium Toxicity Research
- Renal Transplantation Outcomes and Treatments
- Immune Cell Function and Interaction
- Otitis Media and Relapsing Polychondritis
- Systemic Lupus Erythematosus Research
- Inflammasome and immune disorders
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Immunotherapy and Immune Responses
- Urticaria and Related Conditions
- Blood Coagulation and Thrombosis Mechanisms
- Autoimmune Bullous Skin Diseases
- Organ Transplantation Techniques and Outcomes
- Chronic Kidney Disease and Diabetes
- Atherosclerosis and Cardiovascular Diseases
- Complement system in diseases
- COVID-19 Clinical Research Studies
- Immune Response and Inflammation
- Systemic Sclerosis and Related Diseases
- Immunodeficiency and Autoimmune Disorders
The Royal Free Hospital
2015-2024
University College London
2015-2024
Roland Hill (United Kingdom)
2013-2024
Cardiff University
2024
Nantes Université
2024
University College London Hospitals NHS Foundation Trust
2023
Institute of Infection and Immunity
2023
Creative Commons
2023
University of Cape Town
2022
Royal London Hospital
1990-2021
Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) and microscopic polyangiitis. Its cause unknown, there debate about whether it single disease entity what role ANCA plays in its pathogenesis. We investigated genetic basis.
Programmed death-1 (PD-1) receptor, an inhibitory costimulatory molecule found on activated T cells, has been demonstrated to play a role in the regulation of immune responses and peripheral tolerance. We investigated this pathway development autoimmune diabetes. PD-1 or PD-L1 but not PD-L2 blockade rapidly precipitated diabetes prediabetic female nonobese diabetic (NOD) mice regardless age (from 1 10-wk-old), although it was most pronounced older mice. By contrast, cytotoxic...
Experimental autoimmune encephalomyelitis (EAE) is mediated by autoantigen-specific T cells dependent on critical costimulatory signals for their full activation and regulation. We report that the programmed death-1 (PD-1) pathway plays a role in regulating peripheral tolerance murine EAE appears to be major contributor resistance of disease induction CD28-deficient mice. After immunization with myelin oligodendrocyte glycoprotein (MOG) there was progressive increase expression PD-1 its...
Abstract Objective B cell depletion with rituximab has allowed remissions in relapsing or refractory antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis small studies. The aim of this study was to determine the efficacy and safety for ANCA‐associated a larger multicenter cohort. This permitted comparison dosing regimens, value continuing immunosuppression, investigation ANCA levels as re‐treatment biomarkers. Methods Retrospective, standardized data collection from 65 sequential...
CD8+ T cell depletion renders CD28-deficient mice susceptible to experimental autoimmune encephalomyelitis (EAE). In addition, CD8–/–CD28–/– double-knockout are EAE. These findings suggest a role for cells in the resistance of disease. Adoptive transfer CD8+CD28– into CD8–/– results significant suppression disease, while CD8+CD28+ demonstrate no similar effect on clinical course EAE same recipients. vitro, but not suppress IFN-γ production myelin oligodendrocyte glycoprotein–specific CD4+...
Recent evidence suggests that a population of professional regulatory cells, which limit immune responsiveness, exist in rodents and healthy human subjects. However, their role disease states remains unclear. A proportion renal transplant recipients do not demonstrate vitro reactivity toward mismatched donor-derived HLA-DR antigens; it was therefore hypothesized this may be due to such cells. cohort 23 studied at single institution. In patients with no history acute rejection, 6 (40%) 15...
Experimental autoimmune encephalomyelitis (EAE) is mediated by myelin-specific CD4+ T cells secreting Th1 cytokines, while recovery from disease associated with expression of Th2 cytokines. Investigations into the role individual cytokines in induction have yielded contradictory results. Here we used animals targeted deletion STAT4 or STAT6 genes to determine these signaling molecules EAE. The pathway controls differentiation a phenotype, phenotype. We found that mice deficient are resistant...
Background. The Th17 subset has been implicated in the pathogenesis of a number autoimmune diseases. However, little is known about its role anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). We measured serum levels IL-17A and associated upstream cytokines frequency IL-17-producing autoantigen-specific T cells patients with AAV. Methods. ELISA on sera from acute (n = 28) convalescent 65) AAV Hammersmith Hospital was performed for IL-23, IL-6 IL-1β, as well Th1 cytokine...
Abstract Objective To investigate the efficacy of rituximab in patients with refractory ophthalmic Wegener's granulomatosis (WG). Methods Data from 10 consecutive WG treated were retrospectively reviewed. In all patients, disease was driving treatment decisions, and activity had persisted despite standard immunosuppressive treatment. Patients scleritis (n = 3), orbital granulomas causing optic nerve compromise 4), or a combination both conditions 3). All been at least 3 different agents, 5...
Programmed death-1 (PD-1), an inhibitory receptor up-regulated on activated T cells, has been shown to play a critical immunoregulatory role in peripheral tolerance, but its alloimmune responses is poorly understood. Using novel alloreactive TCR-transgenic model system, we examined the functions of this pathway regulation CD4+ cell vivo. PD-L1, not PD-1 or PD-L2, blockade accelerated MHC class II-mismatched skin graft (bm12 (I-Abm12) into B6 (I-Ab)) rejection similar manner CTLA-4 blockade....
Human B cells with immunoregulatory properties in vitro (Bregs) have been defined by the expression of IL-10 and are enriched various B-cell subsets. However, proinflammatory cytokine subsets is largely unexplored. We examined profiles human PBMCs found that CD24hiCD38hi transitional (TrBs), CD24hiCD27+ memory cells, naïve express TNF-α simultaneously. TrBs had highest IL-10/TNF-α ratio suppressed helper T cell 1 (Th1) autologous more potently than did, despite similar expression. Whereas...
The mechanisms by which anti-neutrophil cytoplasmic antibodies (ANCAs) may contribute to the pathogenesis of ANCA-associated vasculitis are not well understood. In this study, both polyclonal ANCAs isolated from patients and chimeric proteinase 3–ANCA induced release neutrophil microparticles primed neutrophils. These expressed a variety markers, including ANCA autoantigens 3 myeloperoxidase. They bound endothelial cells via CD18-mediated mechanism an increase in intercellular adhesion...
Current guidelines advise that rituximab or cyclophosphamide should be used for the treatment of organ-threatening disease in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), although few studies have examined efficacy and safety these agents combination. We conducted a single-centre cohort study 66 patients treated with combination oral corticosteroids, low-dose pulsed intravenous followed by maintenance regimen azathioprine tapered steroid biopsy-proven renal...
Objectives. ANCA-associated vasculitis and interstitial lung disease (ILD) are uncommon conditions. The occurrence of both diseases in the same patient is increasingly recognized. Our aim was to ascertain characteristics outcomes patients with ILD vasculitis. Methods. A retrospective observational cohort study performed. Patients who presented Hammersmith Hospital, London, [granulomatosis polyangiitis (Wegener's), microscopic (MPA) or Churg–Strauss syndrome] also had were included. Following...
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...
ANCA-associated vasculitis is commonly found in elderly patients, but there are few data concerning outcome and treatment the highest age groups.Consecutive patients (N=151) presenting between 1997 2009 were retrospectively included from local registries six centers Sweden, United Kingdom, Czech Republic if diagnosed with microscopic polyangiitis or granulomatosis at ≥75 years during study period. Patients followed until 2 diagnosis death. Data on survival renal function analyzed respect to...
Intravenous pulse methylprednisolone (MP) is commonly included in the management of severe ANCA associated vasculitis (AAV) despite limited evidence benefit. We aimed to evaluate outcomes patients who had, or had not received MP, along with standard therapy for remission induction AAV. retrospectively studied 114 consecutive from five centres Europe and United States a new diagnosis AAV (creatinine > 500 μmol/L dialysis dependency) that (plasma exchange, cyclophosphamide high-dose oral...
Patients receiving hemodialysis are at high risk from coronavirus disease 2019 (COVID-19) and demonstrate impaired immune responses to vaccines. There have been several descriptions of their immunologic severe acute respiratory syndrome 2 (SARS-CoV-2) vaccination, but few studies described the clinical efficacy vaccination in patients on hemodialysis.In a multicenter observational study London population undergoing surveillance PCR testing during period vaccine rollout with BNT162b2 AZD1222,...
Membranous glomerulonephritis (MGN) is a common cause of nephrotic syndrome in adults, mediated by glomerular antibody deposition to an increasing number newly recognised antigens. Previous case reports have suggested association between patients with anti-contactin-1 (CNTN1)-mediated neuropathies and MGN. In observational study we investigated the pathobiology extent this potential MGN examining antibodies against CNTN1 clinical features cohort 468 suspected immune-mediated neuropathies,...