A5050093551- T-cell and B-cell Immunology
- Systemic Lupus Erythematosus Research
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Rheumatoid Arthritis Research and Therapies
- Immunotherapy and Immune Responses
- Chronic Lymphocytic Leukemia Research
- Immunodeficiency and Autoimmune Disorders
- Autoimmune and Inflammatory Disorders Research
- Atherosclerosis and Cardiovascular Diseases
- Cytokine Signaling Pathways and Interactions
- Lymphoma Diagnosis and Treatment
- Peripheral Neuropathies and Disorders
- Psoriasis: Treatment and Pathogenesis
- Phagocytosis and Immune Regulation
- Blood groups and transfusion
- Renal Diseases and Glomerulopathies
- Complement system in diseases
- Cytomegalovirus and herpesvirus research
- Mycobacterium research and diagnosis
- Systemic Sclerosis and Related Diseases
- Spondyloarthritis Studies and Treatments
- Process Optimization and Integration
- DNA Repair Mechanisms
- CAR-T cell therapy research
University College London
2016-2025
University College Hospital
2010-2025
University College London Hospitals NHS Foundation Trust
2012-2022
Comprehensive Clinical Trials
2022
The Royal Free Hospital
2022
University of Birmingham
2022
Versus Arthritis
2022
Center for Rheumatology
1996-2021
Imperial College London
2002-2021
Leiden University Medical Center
2021
Regulatory T cells have been clearly implicated in the control of disease murine models autoimmunity. The paucity data regarding role these lymphocytes human autoimmune has prompted us to examine their function patients with rheumatoid arthritis (RA). (CD4+CD25+) isolated from active RA displayed an anergic phenotype upon stimulation anti-CD3 and anti-CD28 antibodies, suppressed proliferation effector vitro. However, they were unable suppress proinflammatory cytokine secretion activated...
Patients with rheumatoid arthritis have fewer regulatory B cells decreased function, which may be associated inflammation.
To gain preliminary evidence for the safety and efficacy of B lymphocyte depletion therapy in refractory systemic lupus erythematosus (SLE).Six female patients with active SLE, resistant to standard immunosuppressive therapy, were treated on an open-label basis. During a 2-week period, each patient received two 500-mg infusions rituximab, 750-mg cyclophosphamide, high-dose oral corticosteroids.No significant adverse events observed during followup. Patient 1 had not improved at 3 months but...
Abstract Objective To study the quantitative and phenotypic reconstitution of peripheral blood B cells its relationship to dynamics clinical response in patients with rheumatoid arthritis (RA) following cell depletion rituximab. Methods Twenty‐four active RA treated rituximab were studied. Flow cytometry combinations monoclonal antibodies T subsets was used. Results The frequency total number CD19+ decreased a mean 97% for more than 3 months all but 1 patient therapy. All populations...
Abstract The immune system contains natural regulatory cells important in the maintenance of tolerance. Although this suppressive function is usually attributed to CD4 T cells, recent reports have revealed an immunoregulatory role for IL-10-producing B context several autoimmune diseases including collagen-induced arthritis. In present study, we attribute a cell subset expressing high levels CD21, CD23, and IgM, previously identified as transitional 2-marginal zone precursor (T2-MZP) cells....
The induction of regulatory T (T reg) cells holds considerable potential as a treatment for autoimmune diseases. We have previously shown that CD4+CD25hi reg isolated from patients with active rheumatoid arthritis (RA) defect in their ability to suppress proinflammatory cytokine production by CD4+CD25− cells. This defect, however, was overcome after anti–tumor necrosis factor (TNF)-α antibody (infliximab) therapy. Here, we demonstrate infliximab therapy gives rise CD4+CD25hiFoxP3+ cell...
Abstract Objective To explore the changes in serologic variables and clinical disease activity following B lymphocyte depletion 22 patients with rheumatoid arthritis (RA). Methods was attained using combination therapy based on monoclonal anti‐CD20 antibody rituximab. Levels of a indicator inflammation, C‐reactive protein (CRP), antimicrobial antibodies, autoantibodies including IgA‐, IgM‐, IgG‐class factors (RF), antibodies to cyclic citrullinated peptide (anti‐CCP) were assayed. Results...
Abstract IL-10–producing B cells, also known as regulatory cells (Bregs), play a key role in controlling autoimmunity. In this study, we report that chimeric mice specifically lacking (IL-10−/−B cell) developed an exacerbated arthritis compared with wild-type (WT) cell mice. A significant decrease the absolute numbers of Foxp3 T (Tregs), their expression level Foxp3, and marked increase inflammatory Th1 Th17 were detected IL-10−/− WT Reconstitution arthritic deficient (μMT) different subsets...
To assess the clinical and basic serological consequences of B-cell depletion with rituximab in treatment patients systemic lupus erythematosus (SLE) who have failed conventional immunosuppression.An open study 24 severe SLE followed for a minimum 3 months is reported. In majority (19 out 24), 6 follow-up data are described. Disease activity these was assessed every 1-2 using British Isles Lupus Assessment Group (BILAG) system estimates anti-double-stranded DNA antibodies serum C3 levels....
The ultimate goal for the treatment of autoimmunity is to restore immunological tolerance. Regulatory T cells (Treg) play a central role in immune tolerance, and Treg functional abnormalities have been identified different autoimmune diseases, including rheumatoid arthritis (RA). We previously shown that natural from RA patients are competent at suppressing responder cell proliferation but not cytokine production. Here, we explore hypothesis this defect linked with expression function...
Abstract We have previously reported that IL-10+ regulatory B cells, known to play an important role in controlling autoimmunity and inflammatory disorders, are contained within the transitional 2 immature (T2) cell pool (T2 Bregs). Therapeutic strategies facilitating their enrichment or enhancing suppressive activity highly attractive. In this study, we report agonistic anti-CD40 specifically targets T2 cells enriches Bregs upon short-term vitro culture. Although transfer of unmanipulated...
To describe the 6-month clinical outcome and long-term safety profile of B cell depletion therapy (BCDT) in 50 patients with active systemic lupus erythematosus (SLE), who were nonresponsive or poorly responsive to conventional immunosuppression.All except 4 SLE received 1 gm rituximab, 750 mg cyclophosphamide, 100-250 methylprednisolone, administered on 2 occasions weeks apart, achieve depletion. Clinical was assessed using British Isles Lupus Assessment Group (BILAG) activity index serial...
Affinity maturation of B cells in germinal centers (GCs) is a process evolution, involving random mutation immunoglobulin genes followed by natural selection T cells. Only that have acquired antigen are able to interact with Antigen acquisition dependent on the interaction immune complexes inside GCs. It not clear how efficient maintained while their affinity matures. Here we show cells’ own secreted products, antibodies, regulate GC limiting access. By manipulating response monoclonal...
The complement system is an important component of the innate immune response to bacterial pathogens, including Streptococcus pneumoniae . classical pathway activated by antibody–antigen complexes on surface and has been considered predominately be effector adaptive response, whereas alternative mannose-binding lectin pathways are directly cell components effectors response. Recently, a role suggested for during immunity that natural IgM or acute-phase bound pathogens. However, functional...
Serum immunoglobulin (Ig)M provides the initial response to foreign antigen and plays a regulatory role in subsequent immune development, accelerating production of high-affinity IgG. Here we show that mice deficient serum IgM have an increased propensity spontaneous autoimmunity as judged by development with age IgG anti-DNA antibodies renal deposition complement. They also exhibit augmented on exposure lipopolysaccharide. Thus, deficiency leads diminished responsiveness antigens but self—a...
Background— Immunoglobulin M (IgM) natural antibodies bind oxidatively-modified low-density lipoprotein (LDL) and apoptotic cells have been implicated as being important for protection against atherosclerosis. We directly investigated the requirement IgM by studying effects of deficiency in LDL receptor–deficient ( Ldlr −/− ) mice. Methods Results— Mice deficient serum (sIgM) or complement C1q were crossed with mice studied on both low-fat high-fat semisynthetic diets. On diets, en face...
Accelerated development of the secondary immune response may be attributable in part to rapid delivery antigen lymphoid follicles by circulating antibody elicited on primary immunization. Here we provide evidence indicating that nonspecific IgM present naive mice (natural antibody) plays a role acceleration response. Targeted deletion Ig μ s polyadenylation site use Cre recombinase allowed creation that, although harboring normal number B cells expressing surface IgM, completely lacked serum...