A5023290270- Systemic Lupus Erythematosus Research
- Monoclonal and Polyclonal Antibodies Research
- Rheumatoid Arthritis Research and Therapies
- T-cell and B-cell Immunology
- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- Systemic Sclerosis and Related Diseases
- Cytokine Signaling Pathways and Interactions
- Autoimmune and Inflammatory Disorders Research
- Atherosclerosis and Cardiovascular Diseases
- Vasculitis and related conditions
- Otitis Media and Relapsing Polychondritis
- Autoimmune Bullous Skin Diseases
- Immunotherapy and Immune Responses
- Salivary Gland Disorders and Functions
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cell Adhesion Molecules Research
- Immune Cell Function and Interaction
- Peripheral Neuropathies and Disorders
- Renal Diseases and Glomerulopathies
- Musculoskeletal synovial abnormalities and treatments
- Spondyloarthritis Studies and Treatments
- Psoriasis: Treatment and Pathogenesis
- Diabetes and associated disorders
Leeds Teaching Hospitals NHS Trust
2016-2025
NIHR Leeds Musculoskeletal Biomedical Research Unit
2016-2025
University of Leeds
2016-2025
Chapel Allerton Hospital
2013-2023
Universidad Científica del Sur
2023
Hospital Provincial de Rosario
2023
Hospital Clínic de Barcelona
2023
AstraZeneca (Brazil)
2023
Roche (Switzerland)
2023
AstraZeneca (Canada)
2023
To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR).This international initiative had four phases. 1) Evaluation antinuclear antibody (ANA) as an entry criterion through systematic review meta-regression literature generation Delphi exercise, early patient cohort, a survey. 2) Criteria reduction nominal group technique exercises. 3) definition weighting...
<h3>Objective:</h3> Primary Sjögren syndrome (pSS) causes significant systemic symptoms including fatigue as well glandular dysfunction. There are currently no effective therapies; however, open label series have suggested that rituximab may be beneficial for and manifestations. Therefore, we performed a double blind, placebo-controlled, randomised pilot study of the efficacy in reducing pSS. <h3>Methods:</h3> A total 17 patients with pSS score on visual analogue scale (VAS) >50 were to...
Objectives To update the EULAR recommendations for management of systemic lupus erythematosus (SLE) based on emerging new evidence. Methods An international Task Force formed questions systematic literature reviews (January 2018–December 2022), followed by formulation and finalisation statements after a series meetings. A predefined voting process was applied to each overarching principle recommendation. Levels evidence strengths recommendation were assigned, participants finally provided...
Infectious diseases and vaccines can occasionally cause new-onset or flare of immune-mediated (IMDs). The adjuvanticity the available SARS-CoV-2 is based on either TLR-7/8 TLR-9 agonism, which distinct from previous a common pathogenic mechanism in IMDs.We evaluated IMD flares new disease onset within 28-days vaccination at five large tertiary centres countries with early adoption, three Israel, one UK, USA. We assessed pattern expression terms autoimmune, autoinflammatory, mixed phenotype...
Objective. To evaluate the effect of rituximab (RTX) in patients with RA-related interstitial lung disease (RA-ILD) and identify factors associated outcome after treatment. Methods. An observational study RA-ILD was conducted from a cohort RTX-treated RA single centre for >10 years. Progression defined by any following: decrease pre-RTX forced vital capacity (FVC) >10% or diffusion carbon monoxide (DLCO) >15% predicted, worsening ILD score death progressive ILD. Results. Of 700 treated RTX,...
Objectives To characterise the efficacy and safety of anifrolumab in patients with systemic lupus erythematosus (SLE) according to interferon gene signature (IFNGS), demographic clinical subgroups. Methods We performed post hoc analyses pooled data from 52-week phase III TULIP-1/TULIP-2 placebo-controlled trials intravenous moderate-to-severe SLE. Outcomes were assessed predefined subgroups: IFNGS (high/low), age, sex, body mass index, race, geographic region, age onset, glucocorticoid use,...
Concerns have been raised regarding the reduced immunogenicity of vaccines against COVID-19 in patients with autoimmune diseases treated rituximab. However, incidence and severity breakthrough infections unbiased samples specific rheumatic musculoskeletal are largely unknown. We aimed to assess SARS-CoV-2 infection, compare rates moderate-to-severe any severe infection event, evaluate predictors outcomes rituximab.We did a retrospective cohort study all rituximab-treated single centre Leeds,...
Introduction Anifrolumab is a type I interferon (IFN) receptor 1 (IFNAR1) blocking antibody approved for treating patients with systemic lupus erythematosus (SLE). Here, we investigated the immunomodulatory mechanisms of anifrolumab using longitudinal transcriptomic and proteomic analyses 52-week, randomised, phase 3 TULIP-1 TULIP-2 trials. Methods Patients moderate to severe SLE were enrolled in received intravenous or placebo alongside standard therapy. Whole-blood expression 18 017 genes...
Abstract The B cell–depleting monoclonal antibody rituximab is a novel therapy for the rheumatic diseases, with an increasing body of evidence regarding its safety and efficacy in expanding range indications. However, there uncertainty over potential use in, impact on, autoantibody‐negative diseases. We describe 3 patients, no known risk factor psoriasis, who developed psoriasis (and 1 also features psoriatic arthritis) after receiving variety indications, namely, seropositive seronegative...
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...
In rheumatoid arthritis (RA), B cell depletion occurs in all patients treated with rituximab, but the clinical responses to rituximab are variable. A highly sensitive assay was used test hypothesis that is variable, and incomplete leads a poorer outcome.Sixty active RA unresponsive anti-tumor necrosis factor agents received two 1-gram infusions of rituximab. numbers were measured by flow cytometry before after each infusion at 3-month intervals thereafter. reduction levels below...
Abstract Autoimmune connective tissue diseases arise in a stepwise fashion from asymptomatic preclinical autoimmunity. Type I interferons have crucial role the progression to established autoimmune diseases. The cellular source and regulation disease initiation of these cytokines is not clear, but plasmacytoid dendritic cells been thought contribute excessive type interferon production. Here, we show that autoimmunity systemic lupus erythematosus, are effector cells, lost capacity for...
To assess factors associated with primary and secondary non-response to rituximab in systemic lupus erythematosus (SLE) evaluate management of non-depletion (2NDNR).125 patients SLE treated over 12 years were studied prospectively. A major clinical response was defined as improvement all active British Isles Lupus Assessment Group (BILAG)-2004 domains grade C/better no A/B flare. Partial responders by one persistent BILAG B. B-cell subsets measured using highly sensitive flow cytometry....
To evaluate predictors of serious infection events (SIEs) during rituximab (RTX) therapy and effects hypogammaglobulinemia on SIE rates, humoral response its persistence after discontinuation RTX in the treatment rheumatic musculoskeletal diseases (RMDs).A retrospective longitudinal study 700 RMD patients treated with a single center was conducted. Immunoglobulin levels were measured at baseline 4-6 months each cycle. Baseline SIEs assessed using multivariable logistic regression; for cycles...
Objective To evaluate clinical, interferon and imaging predictors of progression from ‘At Risk’ to autoimmune connective tissue diseases (AI-CTDs). Methods A prospective observational study was conducted in At-Risk AI-CTD (defined as antinuclear antibody (ANA) positive; ≤1 clinical systemic lupus erythematosus (SLE) criterion; symptom duration <12 months treatment-naïve). Bloods skin biopsy (non-lesional) were analysed for two interferon-stimulated gene expression scores previously...
The immunopathogenesis of systemic lupus erythematosus (SLE) is heterogeneous, and responses skin to rituximab are variable. This study was undertaken determine the phenotype rituximab-responsive disease.Eighty-two patients with SLE who were receiving prospectively studied. Of these patients, 32 had significant involvement before or after treatment. Disease activity assessed using British Isles Lupus Assessment Group (BILAG) index 2004. Cutaneous subtype classified by a dermatologist as...
Abstract Measurement of type I interferon (IFN-I) has potential to diagnose and stratify autoimmune diseases, but existing results have been inconsistent. Interferon-stimulated-gene (ISG) based methods may be affected by the modularity ISG transcriptome, cell-specific expression, response IFN-subtypes bimodality expression. We developed clinically validated a 2-score system (IFN-Score-A -B) using Factor Analysis 31 ISGs measured TaqMan selected from 3-IFN-annotated modules. evaluated these...
Background Systemic lupus erythematosus (SLE) management objectives include preventing disease flares while minimizing glucocorticoid exposure. Pooled data from the phase 3 TULIP-1 and TULIP-2 trials in patients with moderate to severe SLE were analyzed determine anifrolumab’s effect on flares, including those arising taper. Methods randomized, placebo-controlled, 52-week of intravenous anifrolumab (300 mg every 4 weeks for 48 weeks). For receiving baseline ≥10 mg/day, attempted taper ≤7.5...