Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selective B-cell depletion with anti-CD20 therapy is a promising novel treatment option for patients with refractory autoimmune disease. The anti-CD20 antibody, rituximab, is the first therapeutic monoclonal antibody to have been approved by the European Medical Agency (EMEA) and the US Food and Drug Administration (FDA) for the treatment of relapsed, low-grade, follicular non-Hodgkin's lymphoma. Rituximab is now being studied in a range of autoimmune diseases, most notably rheumatoid arthritis, but also chronic immune thrombocytopenic purpura and systemic lupus erythematosus. Current data obtained from studies of rituximab single-agent therapy for autoimmune disease show good tolerability and sustained improvement in disease symptoms, although the precise mechanisms of action in autoimmunity remain to be fully clarified. Future research is likely to be focused on the optimization of responses with rituximab-based therapy. However, early observations suggest that this approach is likely to yield significant clinical benefits in a wide range of organ-specific and systemic autoimmune diseases.
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PMID:B cells as a therapeutic target in autoimmune diseases other than rheumatoid arthritis. 1585 22

The levels and types of immune responses are determined dependent on the extent of pathogen invasion, reactions to antigens mediated by macrophage-dendritic cells, T cells and antibodies. Recently, accumulating evidence suggests that B cells also play an important role in the regulation of immune responses. Here we have made a review to present a role of B cells in determining the level of immune responses and discussed about the clinical significance of B cell-targeted therapy in patients with autoimmune diseases. Type 1 diabetes is a T cell-mediated autoimmune disease characterized by the destruction of insulin-producing pancreatic beta cells. We and other groups have elucidated that B cells play a critical role in the development of insulitis and diabetes, as B-cell-deficient NOD mice are protected from developing type 1 diabetes. B cells are essential for the T cell receptor clonotype spreading of islet-infiltrating T cells, indicating that B cells may play a role in determining the level of immune responses by antigen presentation to antigen specific T cells. There are now numerous case reports and small series of clinical trials regarding rituximab therapy in autoimmune diseases, such as refractory autoimmune hemolytic anemia, IgM antibody-associated polyneuropathy, systemic lupus erythematosus and rheumatoid arthritis. Rituximab is a genetically engineered chimeric anti-CD 20 monoclonal antibody that is approved for the treatment of lymphoma. CD20 is a B-cell surface antigen that is expressed only on pre- B and mature B cells. Thus, rituximab causes a selective transient depletion of the CD20+ B -cell subpopulation. Rationale and strategy for targeting B cells in the treatment of autoimmune diseases consist of the inhibition of antigen-presentation and co-stimulation that induces T cell expansion and activation. Further careful mechanistic studies are required to develop therapies in patients with autoimmune diseases.
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PMID:[B cells as key contributors in determining the level of immune responses -B-cell-targeted therapy in patients with autoimmune diseases]. 1599 5

New therapeutic approaches that include depletion of B cells using rituximab, a chimeric monoclonal antibody directed against the B cell specific antigen CD-20 have been developed for the treatment of systemic lupus erythematosus (SLE). We report the case of a 18 years old girl with SLE that did not respond and experienced adverse effects with the use of hydroxycloroquine, methotrexate, mycophenolate mofetil, azathioprine and high-dose steroids. Rituximab was given weekly at 375 mg/m(2) for four doses. The drug was well tolerated and the patient had no adverse reactions. She remains asymptomatic three months later.
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PMID:[Rituximab (anti-CD20 monoclonal antibody) for refractory systemic lupus erythematosus: report of one case]. 1607 33

Therapy of systemic lupus erythematosus (SLE) with major organ involvement consists of aggressive immunosuppression with glucocorticoids and cytotoxic agents. When remission is achieved, maintenance therapy is begun to reduce the risk of relapse while minimizing toxicity. Remission with standard therapy is, however, not always achieved. We discribe a women with SLE and microangiopathic haemolytic anaemia and thrombocytopenia, pneumonitis and nephritis refractory to high-dose steroids, pulse cyclophosphamide, plasmapheresis and intravenous immunoglobulins. The anti-CD20 monoclonal antibody rituximab was administered, resulting in major clinical and biochemical improvement. Therapy-resistant SLE generally has an ominous prognosis. A few anecdotal reports and small open studies describe beneficial effects of rituximab in these cases. Rituximab may be a promising new approach to improve the dismal outcome of therapy-resistant SLE.
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PMID:Management of therapy-resistant systemic lupus erythematosus with rituximab: report of a case and review of the literature. 1608 97

Rituximab is a genetically engineered chimeric monoclonal immunoglobulin (Ig)G1 antibody. It binds the CD20 trans-membrane surface antigen expressed by mature B cells but not by antibody secreting plasma cells, and removes the cells by activating complement, inducing cell-mediated lysis, and by apoptosis. Mainly used for the treatment of non-Hodgkin's lymphomas, rituximab has recently been tried with favourable responses in rheumatoid arthritis, systemic lupus erythematosus, and other chronic immunological diseases. Wegener's granulomatosis (WG) is a granulomatous vasculitis with high morbidity and mortality. It is thought that anti-neutrophil cytoplasmatic antibodies (ANCA) with specificity for proteinase 3 (PR3) are possibly involved in the pathogenesis of the disease. Conventional therapy with cyclophosphamide and corticosteroids generally succeeds in inducing remission, but relapses frequently follow. Among the biological agents, tumour necrosis factor-alpha (TNF-alpha) inhibitors have been tried with some success. Based on a case report we recently treated three refractory WG patients with rituximab and achieved almost complete but temporary remission. CD20+ cells disappeared rapidly in peripheral blood, only to rise prior to subsequent disease flares occurring at 34, 63, and 54 weeks, respectively (Figure 1). A new flare occurred in one patient at 86 weeks. At the end of the observation periods (54, 102, and 120 weeks), only one patient had proteinuria. Chest radiographs became normal in two patients, while infiltrates remained unchanged in the third. Granulomatous retro-orbital or sinus masses in two patients seemed unresponsive to therapy.
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PMID:Anti-CD20 therapy of treatment-resistant Wegener's granulomatosis: favourable but temporary response. 1613 30

B-cells play a major role in the immunopathogenesis of autoimmune diseases. Not only do they produce autoantibodies, but they regulate other cell types, secrete cytokines, and present antigens. They are thus potential targets for therapeutic intervention. CD20 is a B-cell specific cell surface molecule of uncertain function. An anti-CD20 chimeric mAb (rituximab) has been FDA approved for treatment of B-cell lymphomas since 1997. Rituximab also depletes normal B-cells by several mechanisms, including ADCC. Over the past seven years, it has shown promise in a number of autoimmune diseases in phase I trials and anecdotal reports. Efficacy in rheumatoid arthritis has already been demonstrated in randomized control trials (RCTs), and RCTs in SLE, inflammatory myositis, and ANCA associated vasculitis are under way. Safety does not appear to be a major problem, but continued vigilance is warranted. The increased use of rituximab, other anti-CD20 agents, and other B-cell targeting therapies holds great promise for substantial clinical benefits, as well as providing special opportunities to understand better disease pathogenesis.
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PMID:The therapeutic potential of anti-CD20 "what do B-cells do?". 1616 73

After improvement of the prognosis of the primary systemic vasculitides and systemic lupus erythematosus from a desperate diagnosis with hardly a one year survival after diagnosis to a 5-year-survival-rate of more than 90% actual therapeutic regimes aim at those patients refractory to standard therapeutic regimes, not achieving a remission by standard approaches or having organ damage or contraindications. Furthermore less toxic regimes are looked for with the aim to avoid secondary complications of the standard therapy. New drugs used successfully in rheumatology, transplantation medicine and haematology are used for these purposes in the last years. Recent experiences with Infliximab, Mycophenolate Mofetil, Rituximab und Deoxyspergualin for the treatment of the small vessel vasculitides and systemic lupus erythematosus are reviewed.
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PMID:[New therapeutic concepts for vasculitis and collagenosis]. 1626 76

Recent studies have revealed that B cells play a critical role in autoimmunity and disease expression through various functions, including autoantibody production, cytokine secretion, antigen presentation, and co-stimulatory effect. Selective targeting of B cells has been recently achieved using a chimeric monoclonal antibody against CD20 (Rituximab). Significant clinical efficacy has been demonstrated in several autoimmune diseases including rheumatoid arthritis and systemic lupus erythematosus by the infusion of this antibody. Rituxumab significantly improves the symptoms during the long period of complete B cell depletion. Understanding the dynamics of B cell involvement in autoimmune diseases will be crucial to the development of B cell-targeted strategies. Conversely, the findings derived from studies of anti-B cell therapy provide us a lot of important clues to clarify the pathogenesis of autoimmune diseases. This review focuses on recent data demonstrating the roles of B cells in autoimmune diseases as well as the current studies concerning the treatment of autoimmune diseases by Rituximab.
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PMID:[B lymphocyte]. 1627 43

Several trials of new immunologic agents in systemic lupus erythematosus (SLE) have recently been undertaken. Rituximab, a chimeric antibody directed against CD20 on B lymphocytes, has emerged as a promising therapy. Based upon preliminary data, clinical efficacy of rituximab has been documented in both pediatric and adult-onset SLE patients. The specific manifestations reported to be beneficially affected include lupus nephritis, arthralgia/arthritis, serositis, cutaneous vasculitis, mucositis, rashes, fatigue and neurologic symptoms. Although rituximab's mechanisms of action are incompletely understood, the effects of rituximab are likely mediated by antibody-dependent cell-mediated cytotoxicity and the induction of apoptosis. The resultant repopulation of B cells, alteration of abnormal B cell homeostasis and down-regulation of co-stimulatory molecules on both B and T cells all likely contribute to clinical efficacy. Good tolerability of rituximab is reported with rare serious side effects. The positive response to rituximab verifies a central role for B cells in SLE. This article highlights the clinical experience of rituximab therapy in both pediatric and adult-onset SLE. These data suggest a promising role for rituximab in the treatment of SLE. Further controlled trials and long-term outcome studies are imperative to further define its clinical application and to improve the care of patients.
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PMID:Rituximab: a promising therapy in systemic lupus erythematosus. 1633 7

Rituximab is a chimeric monoclonal antibody that targets the CD20 molecule on the B-cell surface. It is the first antibody of its kind to be licensed for the treatment of non-Hodgkin's lymphoma. Rituximab was found to be effective, well-tolerated and has a good safety profile, though its precise cellular effects are still not well understood. Rituximab has been shown to be of therapeutic benefit in various autoimmune diseases in which B lymphocytes play a role. This article summarizes the current literature regarding the use of rituximab in lymphoma, rheumatoid arthritis, systemic lupus erythematosus and other selected autoimmune diseases.
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PMID:Rituximab. 1647 54


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