Jonathan Edwards

Jonathan Edwards
University College London | UCL · Division of Medicine

BA, MB BCh, MD, FRCP

About

227
Publications
74,899
Reads
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Introduction
Up until 2010 my research programme focused on the mechanisms and treatment of rheumatoid arthritis and related autoimmune disease. Since 2010 my interest has been in the biophysical basis of conscious experience. LINK to homepage: http://www.ucl.ac.uk/jonathan-edwards
Additional affiliations
July 1986 - present
University College London
Position
  • Professor in Connective Tissue Medicine

Publications

Publications (227)
Article
Full-text available
We perceive colour, shape, sound and touch 'bound together' in a single experience. The following arguments about this binding phenomenon are raised: (1) The individual signals passing from neurone to neurone are not bound together, whether as elements of information or physically. (2) Within a single cell, binding in terms of bringing together of...
Article
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An open-label study indicated that selective depletion of B cells with the use of rituximab led to sustained clinical improvements for patients with rheumatoid arthritis. To confirm these observations, we conducted a randomized, double-blind, controlled study. We randomly assigned 161 patients who had active rheumatoid arthritis despite treatment w...
Article
Normal immunological memory is thought to be underpinned by T lymphocytes. However, in rheumatoid arthritis there are indications that T-lymphocyte control has been subverted by self-perpetuating B lymphocytes. Potential mechanisms in other autoimmune states are less clear, but a number of observations suggest that misappropriation of immunological...
Article
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Autoantibody production in patients with systemic lupus erythematosus (SLE) is associated with abnormalities of B cell function and phenotype. Clinical responses to B cell depletion therapy (BCDT), based on rituximab, are encouraging. Therefore, we undertook this study to investigate the effect of BCDT on antibody profiles. Serial sera from 16 pati...
Article
The PACE trial of cognitive behavioural therapy and graded exercise therapy for chronic fatigue syndrome/myalgic encephalomyelitis has raised serious questions about research methodology. An editorial article by Geraghty gives a fair account of the problems involved, if anything understating the case. The response by White et al. fails to address t...
Article
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It is widely perceived that there is a problem in giving a naturalistic account of mental representation that deals adequately with the issue of meaning, interpretation or significance (semantic content). It is suggested here that this problem may arise partly from the conflation of two vernacular senses of representation: representation-as-origin...
Article
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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is comparable to multiple sclerosis, diabetes or rheumatoid arthritis in prevalence (∼0.2% to 1%), long-term disability, and quality of life,[1–5] yet the scale of biomedical research and funding has been pitifully limited, as the recent National Institutes of Health (NIH) and Institute of...
Article
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Rituximab induces clinical remission in a majority of seropositive patients with Rheumatoid arthritis (RA), however, all patients eventually relapse. Although B cell return precedes clinical relapse absolute B cell numbers are not predictive of relapse. The aim of this study was to determine whether there were any consistent dynamic changes in comb...
Article
Background Secondary loss of efficacy to individual treatments in patients with rheumatoid arthritis (RA) is well described. It is not clear whether pharmacokinetic or pharmacodynamic changes have taken place or whether the pathogenic process has changed and is no longer controlled by the previous therapeutic approach. However, secondary loss of ef...
Article
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McFadden has recently raised several cogent points about the problems of 'Gestalt Information' and the meaning of meaning in human experience, in particular the central problem of 'binding'. Very reasonably, he has tried to resolve these problems in terms of a unified electromagnetic field. However, certain premises on which his arguments are based...
Article
Full-text available
It is widely perceived that there is a problem in giving a naturalistic account of mental representation that deals adequately with the issue of meaning (semantic content). It is suggested here that this arises partly from general problems relating to explication of meaning but also, specifically, to the conflation of two vernacular senses of repre...
Article
Objective: Increased cardiovascular risk has been associated with high levels of serum antibodies to citrullinated proteins (ACPA) in patients with rheumatoid arthritis (RA). Citrullination is part of many chronic inflammatory processes and we therefore investigated whether ACPA might be associated with coronary artery disease, in the absence of R...
Conference Paper
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The expression of VH4 gene family during immunoglobulin heavy chain synthesis has been detected in autoimmune diseases. In particular, the rat monoclonal antibody 9G4 detects VH4-34-encoded immunoglobulins and B cells expressing these antibodies as surface receptor (autoreactive 9G4+ B cells).
Article
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To investigate whether levels of serum immunoglobulins (sIgs) at baseline were associated with clinical parameters or B-cell dynamics following rituximab (RTX) in patients with rheumatoid arthritis (RA). Baseline Ig levels, C-reactive protein (CRP), DAS28 and CD19+ve B-cell count (baseline, 1, 3 and 5 months) in 112 patients with RA after 1 cycle o...
Conference Paper
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Background The rat monoclonal antibody 9G4 recognises VH4-34-encoded proteins, enabling the identification of inherently autoreactive B cells. In rheumatoid arthritis (RA), evidence for a humoral immune response encoded by VH4-34 gene has been described in the synovial membrane and within hybridomas derived from rheumatoid synovial tissue. The auth...
Article
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To investigate whether the incidence of secondary hypogammaglobulinaemia in patients with RA following rituximab was related to patterns of B-cell return and relapse. CD19(+) B-cell and serum immunoglobulin (sIg) determinations were done every 2 or 3 months in 137 consecutive patients treated with one or more courses of rituximab-based B-cell deple...
Article
To examine the expression of B-cell-activating factor receptor (BAFF-R) on naive CD27- and memory CD27+ B cells in normal individuals and patients with rheumatoid arthritis (RA) undergoing B-cell depletion therapy with rituximab. Patients and BAFF-R expression on B-cell subsets was determined in normal controls (NC; n = 11), active patients with RA...
Article
Nature Network Groups hosted an invited workshop on 'Theories of Consciousness' during the second semester of 2009. There were presentations by each of 15 authors active in the field, followed by debate with other presenters and invitees. A week was allocated to each of the theories proposed; general discussion threads were also opened from time to...
Article
To describe the 6-month clinical outcome and the 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 of 50 patients with active SLE received 1 gm of rituximab, 750 mg of cyclophosphamide,...
Article
To assess the efficacy of B lymphocyte depletion therapy (BCDT) in patients with refractive idiopathic inflammatory myopathy (IIM). Eight patients thought to have IIM were treated with BCDT utilising rituximab. Five were treated as part of an open label trial and three on the basis of perceived clinical need. Rituximab (1 gram) and methylprednisolo...
Article
To assess the relationships between serum B lymphocyte stimulator (BLyS) levels, autoantibody profile and clinical response in patients with systemic lupus erythematosus (SLE) following rituximab-based B cell depletion therapy (BCDT). A total of 25 patients with active refractory SLE were followed for >or=1 year following BCDT. Disease activity was...
Article
B cell depletion therapy (BCDT) has recently been used with success to treat patients with rheumatoid arthritis and systemic lupus erythematosus (SLE). As antiphospholipid antibodies have been implicated in the pathogenesis of the antiphospholipid syndrome (APS), we asked the question whether BCDT affects levels of IgG anticardiolipin antibodies (a...
Article
It is argued that both neuroscience and physics point towards a similar re-assessment of our concepts of space, time and 'reality', which, by removing some apparent paradoxes, may lead to a view which can provide a natural place for consciousness and language within biophysics. There are reasons to believe that relationships between entities in exp...
Article
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To describe the long-term clinical outcome and safety profile of B cell depletion therapy (BCDT) in patients with systemic lupus erythematosus (SLE). It was also determined whether baseline parameters can predict the likelihood of disease flare. 32 patients with refractory SLE were treated with BCDT using a combination protocol (rituximab and cyclo...
Article
Full-text available
An invited workshop on ‘Theories of Consciousness’ was organized in the format of a Nature Network closed group during the second semester of 2009. There were presentations by each of 15 authors active in the field, followed by debate with other presenters and invitees. A week was allocated to each of the theories proposed; general discussion threa...
Article
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To assess safety and efficacy of repeated B-cell depletion with rituximab in patients with rheumatoid arthritis (RA). Thirty-seven patients with refractory RA entered into a programme of repeated B-lymphocyte depletion (up to 5 cycles, 89 cycles in total) with protocols based on the anti-CD20 monoclonal antibody, rituximab, have been observed over...
Article
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To assess the presence and phenotype of B-lineage cells in the bone marrow (BM) of rheumatoid arthritis (RA) patients after rituximab therapy. Six patients were studied. BM aspirates were collected 3 months after the treatment and analysed using the four-colour flow cytometry. CD19+ (B-lineage) cells in BM samples varied from 0.1 to 3.25% in the ly...
Article
B cell depletion therapy was introduced for auto-antibody associated rheumatic disease in 1998. Encouraging pilot studies in rheumatoid arthritis were followed by randomised controlled trials confirming major benefit. Licensing for use in patients unable to benefit from tumour necrosis factor alpha (TNFalpha) neutralising agents is envisaged shortl...
Article
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To report the clinical outcome and safety profile of repeated B cell depletion in seven patients with refractory systemic lupus erythematosus (SLE). Since June 2000, seven patients with refractory SLE had repeated cycles of B cell depletion (18 cycles in total, up to three cycles per patient) because of disease relapse. The clinical response (asses...
Article
Full-text available
We have examined the frequencies of Tγδ cells in blood, synovial fluids, and synovial membranes of patients with rheumatoid arthritis (RA) and in blood from age-matched controls Immunocyto-chemical and immunohistochemical techniques were used with monoclonal antibodies BB3 and A13 to define a major and minor blood subset of Tγδ cells respectively....
Article
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B-cell-targeted therapy for autoimmune disease emerged from theoretical proposition to practical reality between 1997 and 1998, with the availability of the B-cell-depleting monoclonal antibody rituximab. Since then, a score of autoantibody-associated disorders have been treated, with most convincing evidence of efficacy seen in subjects with rheum...
Article
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To assess the effects of B lymphocyte depletion on serum B lymphocyte stimulator (BLyS; trademark of Human Genome Sciences, Rockville, MD) levels in patients with rheumatoid arthritis (RA), and to assess the relationship of serum BLyS levels with peripheral blood B cell depletion, levels of autoantibodies and antimicrobial antibodies, the return of...
Article
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To study the quantitative and phenotypic reconstitution of peripheral blood B cells and its relationship to the dynamics of clinical response in patients with rheumatoid arthritis (RA) following B cell depletion with rituximab. Twenty-four patients with active RA treated with rituximab were studied. Flow cytometry with combinations of monoclonal an...
Article
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To assess the clinical and basic serological consequences of B-cell depletion with rituximab in the treatment of patients with systemic lupus erythematosus (SLE) who have failed conventional immunosuppression. An open study of 24 patients with severe SLE followed for a minimum of 3 months is reported. In the majority of patients (19 out of 24), 6 m...
Article
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We describe a patient with polymyalgia rheumatica/giant cell arteritis (PMR/GCA) whose disease was refractory to a reduction in the dose of her glucocorticoid to an acceptable level. Our patient improved after B lymphocyte depletion but developed respiratory problems. To our knowledge this is the first description of such a case. An 82 year old wo...
Article
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Reasons for targeting B cells in autoimmune disease date back to the discovery of autoantibodies over 50 yr ago (1). The idea became of practical interest when anti-B cell monoclonal anti- bodies were developed in the early 1990s (2, 3). Fortuitously, at about the same time it became clear that B cells are not simply the subordinate foot soldiers o...
Article
During the 1990s evidence emerged to suggest that B lymphocyte depletion in rheumatoid arthritis (RA) might be of major benefit. In 1997 the B lympholytic monoclonal anti-CD20 antibody rituximab became available. Significant clinical efficacy has been demonstrated in RA, initially in open studies at University College London and recently in a multi...
Chapter
Since the anti-CD20 therapeutic monoclonal antibody rituximab became available for clinical use in 1997 the effects of B lymphocyte depletion (BLyD) have been explored in a range of autoimmune disorders (Edwards et al., 2002). The results of a formal controlled trial in rheumatoid arthritis (RA) confirm that clinical benefit can be substantial (Edw...
Article
B lymphocyte depletion therapy in rheumatoid arthritis can provide major clinical benefits. Widespread use in the future will depend on continued evidence of safety, particularly in the context of long term use. Rituximab is a highly effective agent, but it may be best used in combination with other agents. Substantial improvement following a singl...
Article
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To investigate the distribution of lymphatic vessels in normal, rheumatoid arthritis (RA) and osteoarthritis (OA) synovium. Synovial tissues from 5 normal controls, 14 patients with RA, and 16 patients with OA were studied. Lymphatic vessels were identified by immunohistochemistry using antibodies directed against the lymphatic endothelial hyaluron...
Article
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Cartilage glycosaminoglycan (GAG) synthesis and composition, upon which its structural integrity depends, varies with age, is modified by anabolic and catabolic stimuli, and is regulated by UDP-glucuronate availability. However, how such stimuli, prototypically represented by transforming growth factor-beta1 (TGF-beta1) and IL-1alpha, modify GAG sy...
Article
Cartilage glycosaminoglycan (GAG) synthesis and composition, upon which its structural integrity depends, varies with age, is modified by anabolic and catabolic stimuli, and is regulated by UDP-glucuronate availability. However, how such stimuli, prototypically represented by transforming growth factor-β1 (TGF-β1) and IL-1α, modify GAG synthesis du...
Article
Full-text available
Thirty-seven patients have been recruited to a programme of repeated B-cell depletion therapy for rheumatoid arthritis. Protocols have been based on rituximab, combined with cyclophosphamide initially. Sixty-two treatments have been given over 4.5 years. Patients were withdrawn for inadequate response (< ACR20), for successful reintroduction of dis...
Article
Full-text available
To explore the changes in serologic variables and clinical disease activity following B lymphocyte depletion in 22 patients with rheumatoid arthritis (RA). B lymphocyte depletion was attained using combination therapy based on the monoclonal anti-CD20 antibody rituximab. Levels of a serologic indicator of inflammation, C-reactive protein (CRP), of...
Article
Full-text available
To obtain evidence for dose response and to extend evidence of safety and efficacy for B lymphocyte depletion in rheumatoid arthritis. Twenty two patients with rheumatoid arthritis received a total of 29 treatments with five different combinations of rituximab (RTX), cyclophosphamide (CP), and/or high dose prednisolone (PR) on an open basis as foll...
Article
Full-text available
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 of rituximab, two 7...
Article
Full-text available
B-lymphocyte depletion therapy is being explored in a wide range of autoimmune disorders. In many, there is early evidence for efficacy, and immunosuppression has not been a major problem. The mechanism of action is unclear, but appears to be consistent with the lowering of autoantibody levels, where relevant antibodies are quantifiable. An interes...
Article
The cell surface glycoprotein CD163 is a member of the cysteine-rich scavenger receptor family, highly specific for leukocytes of the mononuclear phagocyte lineage. In vitro, it is induced by glucocorticoids, interleukin-6 (IL-6), and IL-10 and down-regulated by interferon-gamma (IFNgamma), indicating that it has a role in antiinflammatory or other...
Article
An open study of B-lymphocyte depletion was undertaken in rheumatoid arthritis (RA) patients to test the hypothesis that B lymphocytes may be essential to disease perpetuation. Five patients with refractory RA were treated with a monoclonal anti-CD20 antibody, cyclophosphamide and prednisolone and followed for 12-17 months. Patient 2 received furth...
Article
TSG-6 [the product of tumor necrosis factor (TNF)-stimulated gene-6] is a hyaluronan-binding protein that is present in the synovial fluids of arthritis patients and is secreted by cells of articular joints (e.g. chondrocytes and synoviocytes). This study examines the pattern of TSG-6 expression in normal and diseased cartilage and synovium using i...