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)

Rituximab, chimeric anti-human CD20, is approved for treatment of B-cell lymphoma in adults. It is being used experimentally in other various immune-related diseases such as immune thrombocytopenic purpura, systemic lupus erythematosus, myasthenia gravis and rheumatoid arthritis. In transplant recipients, it is used for treatment of post-transplant lymphoproliferative disease, to anecdotally reduce pre-formed anti-HLA and anti-ABO antibodies and for the prevention and treatment of acute rejection. This article primarily reviews the science behind rituximab: its history, pharmacokinetics and potential mechanism of action. A need for controlled clinical trials is clearly indicated before the widespread use of this drug in transplant.
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PMID:Rituximab, an anti-cd20 monoclonal antibody: history and mechanism of action. 1661 21

The rituximab antibody is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. Rituximab is indicated for the treatment of patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin lymphoma. Rituximab is also commonly used to treat chronic lymphocytic leukemia, Waldenstrom's macroglobulinemia, and immune or idiopathic thrombocytopenic purpura (ITP). Rituximab is an effective treatment for primary cutaneous B-cell lymphoma and other cutaneous lymphomas. Rituximab is an effective treatment for mixed cryoglobulinemia. Rituximab is a promising treatment for systemic lupus erythematosus, dermatomyositis, pemphigus, vasculitis, and a variety of hematologic diseases. Black-box warnings on rituximab include fatal infusion reactions, tumor lysis syndrome, and severe mucocutaneous reactions. A variety of cardiac, pulmonary, renal, and hematologic side effects can occur. It commonly causes mild cutaneous side effect and rarely has caused paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis.
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PMID:A review of rituximab in cutaneous medicine. 1663 71

Rituximab is a chimeric monoclonal antibody specific for human CD20 that causes selective transient depletion of the CD20+ B-cell subpopulation. We report the first case of systemic lupus erythematosus (SLE) pneumonitis resistant to conventional treatments that responded well to rituximab and review current reports on the use of rituximab in SLE.
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PMID:Rituximab use in systemic lupus erythematosus pneumonitis and a review of current reports. 1664 Jul 45

We studied the clinical and immunological effects of Rituximab (anti-CD20) therapy in patients with lupus nephritis. In an open clinical trial, 22 patients with active systemic lupus erythematosis and renal involvement (mainly class III and IV according to the WHO classification) that was refractory to conventional therapy were studied. In all these patients, Rituximab (0.5 to 1.0 g at days 1 and 15) was added to the immunosuppressive therapy and its therapeutic effect was evaluated. In addition, the levels and function of regulatory T lymphocytes and the apoptosis of immune cells were assessed. We found a significant reduction in disease activity (p < 0.05, MEX-SLEDAI index), and proteinuria (p < 0.05) at days 60 and 90 of Rituximab therapy. Although most patients showed improvement in creatinine clearance and erythrocyturia, no significant changes in these parameters were detected. In most patients (20/22), B cell depletion was observed, but no clear-cut effect of Rituximab on complement levels or auto-antibody titers was detected (p > 0.05 in all cases). One patient died at day 70 with invasive histoplasmosis. No important adverse effects of Rituximab therapy were registered in other patients. A significant enhancement in the levels of different CD4+ regulatory cells (TREG, Th3, Tr1), but not CD8+ Ts lymphocytes, was observed at day 30. This increase was sustained for TREG cells at day 90, and accompanied by an improvement in their regulatory function. In addition, we observed an unexpected increase in the apoptosis of T cells at day 30. Interestingly, the enhancement in the suppressive function of TREG cells was not observed in the two patients that showed the poorest clinical response to Rituximab. We conclude that the data obtained in this open clinical trial suggest that Rituximab is a promising candidate for randomized controlled trials in patients with lupus nephritis refractory to the conventional immunosuppressive therapy. The effects of Rituximab on regulatory cells and apoptosis of T lymphocytes are interesting and its possible role in the putative effect of this biological agent in systemic lupus erythematosis deserves additional studies.
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PMID:Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study. 1667 95

The aim of this study was to evaluate the response to treatment and the long-term outcome in a cohort of patients in whom severe autoimmune hemolytic anaemia (AHA) was the leading manifestation of systemic lupus erythematosus (SLE). Twenty-six women with severe isolated AHA were included. Corticosteroids were used as the initial treatment for all patients in our study. An initial response was obtained in all but one patient (96%). The overall recurrence rate was three per 100 person-years, with an expected recurrence-free proportion of 73% with a 180 months median follow-up. Seven patients (27%) experienced a relapse of AHA. We found a higher proportion of pleuritis in relapsing patients. Only three patients experienced multiple relapses despite splenectomy and several immunosuppressants. Steroid-sparing effect of hydroxychloroquine and azathioprine could not be assessed because most of the patients received these treatments for other reasons than AHA. Intravenous immunoglobulins induced transient response in three cases. Splenectomy was efficient to definitively control AHA in one patient but two patients quickly experienced relapses while one patient did not benefit. Five patients received immunosuppressants that induced only transient responses. Rituximab was long-term efficient in one case. In conclusion, severe AHA is a serious complication of SLE that warrants appropriate management. On the basis of our experience, the ideal treatment of isolated AHA should be oral corticosteroids in first-line treatment. Our study does not support an important role for splenectomy. Patients refractory to conventional therapy should be treated either with few toxic immunosuppressive drugs, danazol or rituximab.
Lupus 2006
PMID:Treatment of isolated severe immune hemolytic anaemia associated with systemic lupus erythematosus: 26 cases. 1668 62

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 shortly. Open studies in other disorders, in particular systemic lupus erythematosus (SLE), have also suggested benefit and its use in life-threatening situations is becoming widespread. Toxicity appears to compare favourably with other agents, but respiratory problems may be more common. Repeated therapy is effective, but may lead to hypogammaglobulinemia. Rituximab is currently the main agent used but other agents are in development. Optimal protocols are not well characterised and will probably be different for different conditions.
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PMID:B cell depletion therapy in rheumatic disease. 1698 Feb 14

Systemic lupus erythematosus (SLE) is a complex disease characterised by numerous autoantibodies and clinical involvement in multiple organ systems. The immunological events triggering the onset of clinical manifestations have not yet been fully defined, but a central role for B cells in the pathogenesis of this disease has more recently gained prominence as a result of research in both mice and humans. Both antibody-dependent and -independent mechanisms of B cells are important in SLE. Autoantibodies contribute to autoimmunity by multiple mechanisms, including immune complex-mediated type III hypersensitivity reactions, type II antibody-dependent cytotoxicity, and by instructing innate immune cells to produce pathogenic cytokines such as interferon-alpha, tumour necrosis factor and interleukin-1. Suggested autoantibody-independent B-cell functions include antigen presentation, T-cell activation and polarisation, and dendritic-cell modulation. Several of these functions are mediated by the ability of B cells to produce immunoregulatory cytokines, chemokines and lymphangiogenic growth factors, and by their critical contribution to lymphoid tissue development and organisation, including the development of ectopic tertiary lymphoid tissue. Given the large body of evidence implicating abnormalities in the B-cell compartment in SLE, a recent therapeutic focus has been to develop interventions that target the B-cell compartment by multiple mechanisms.Rituximab, a mouse-human chimeric monoclonal antibody against CD20 that specifically depletes B cells, has been studied the most extensively. Although promising open-label data await confirmation in ongoing multicentre placebo-controlled trials, a number of preliminary conclusions can be drawn. The adequacy of peripheral B-cell depletion depends on achieving high and sustained serum rituximab concentrations, pharmacokinetics that can be varied with treatment dose and factors that may affect drug clearance, such as human anti-chimeric antibodies. In SLE patients with effective B-cell depletion, the clinical response can be significant, with favourable responses observed in a diverse array of disease manifestations. Moreover, rituximab appears to have the potential to induce clinical remission in severe, refractory disease. B-cell depletion has the potential to induce disease amelioration by inhibiting autoantibody production and/or by interfering with other B-cell pathogenic functions. The fact that clinical improvement correlates with B-cell depletion and precedes by several months any decline in serum levels of relevant autoantibodies suggests a predominant effect of autoantibody-independent functions of B cells, although the subset of patients with disease remission ultimately also experience autoantibody normalisation. Significant questions remain about rituximab therapy in SLE, including the immunological determinants of treatment response and remission, the role of combination therapy, and the safety of repeated courses of rituximab. In addition, the efficacy and role of other B-cell-depleting approaches, such as humanised anti-CD20 antibodies and anti-CD22, remain to be defined. Another B-cell-targeted therapeutic approach is to block costimulatory interactions between T and B cells. Blockade of the CD40-CD40 ligand pathway has met with variable clinical benefit and unfortunate thromboembolic complications, although inhibition of the B7 pathway with cytotoxic T-lymphocyte antigen-4Ig is currently under early investigation in SLE clinical trials. Preliminary data on the treatment of SLE with belimumab, a fully human monoclonal antibody that specifically binds to and neutralises the B-lymphocyte stimulator (BLyS or B-cell-activating factor [BAFF]), are now available. In a phase II double-blind, placebo-controlled trial of the safety and efficacy of three different doses administered in addition to standard therapy, belimumab was well tolerated but reportedly did not meet primary efficacy endpoints. Blockade of BAFF is still viewed as a promising therapeutic approach and additional agents that interfere with the BAFF pathway are under study.Overall, therapies targeting B cells appear to be promising in the treatment of SLE, provide additional evidence for the importance of B cells to disease pathogenesis, and will continue to elucidate the diverse roles of B cells in this disease.
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PMID:B-cell-targeted therapy for systemic lupus erythematosus. 1710 Apr 5

After many barren years, conceptual advances and the introduction of new biotherapies are yielding improvements in the management of systemic lupus erythematosus (SLE). The result is a radical change in the management strategy. The main therapeutic advances rest on new discoveries (or rediscoveries), some of which are original. They can be summarized under 12 headlines. Smoking is inadvisable, as it promotes not only atheroma but also lupus flares. Hydroxychloroquine and conventional drugs (cyclophosphamide) are helpful provided they are used appropriately. Combined oral contraception and hormone replacement therapy may be less hazardous than previously thought, although caution remains in order. Drugs used in transplant recipients, such as mycophenolic acid, are generating optimism as treatments for SLE. Rituximab and new anti-B-cell drugs hold promise for the treatment of severe SLE. Efforts to develop an "etiologic" treatment for SLE based on type 1 (alpha/beta) interferon blockade still face a number of obstacles. Peptide vaccines, whose main effect is stimulation of regulator T cells, hold promise-but confirmation is needed. Whether TNF antagonists can be used in lupus with skin and joint manifestations or in SLE is generating debate. Complement blockade for treating SLE and antiphospholipid syndrome is an attractive avenue of research. Numerous new immunotherapy modalities based on modulating intracellular signaling are being evaluated. In the most severe forms of SLE, autologous peripheral stem cell transplantation deserves consideration. A key component of the treatment of SLE is control of atheroma, which is among the most severe complications. This rich harvest of new treatment possibilities can be expected to radically modify the prognosis of SLE, whose more aggressive forms remain severe.
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PMID:Treatment of systemic lupus erythematosus in 2006. 1711 Jan 51

B cells play a central role in the pathogenesis of SLE. Not only do they make autoantibodies, but they can provide immunoregulatory controls of T cells, dendritic cells, and other B cells, in part through cytokine production. The availability of a chimeric monoclonal antibody that targets B cells has made it possible to treat SLE by B-cell depletion. Rituximab binds to the B-cell specific antigen CD20, and depletes B cells from the peripheral blood and lymphoid tissues. A growing number of anecdotal series and case reports suggest that rituximab may provide clinical benefit in SLE with acceptable toxicity, although the variability in responses of individual patients is not yet fully understood. Two large ongoing randomized controlled trials will determine the efficacy of rituximab in SLE, both renal and extra-renal, and will inform us better about the biology of the B cell in this disease and the effects of B-cell depletion.
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PMID:Targeting B cells in SLE: the experience with rituximab treatment (anti-CD20). 1721 80

Serum sickness, an illness characterized by fever, rash, and arthralgias, can occur in patients who receive chimeric monoclonal antibody therapy. Rituximab, a B cell-depleting chimeric anti-CD20 monoclonal antibody, has been used with increasing frequency in the treatment of rheumatologic illnesses such as rheumatoid arthritis and systemic lupus erythematosus. Serum sickness has only rarely been reported following rituximab therapy. All prior reported cases have been in patients with autoimmune conditions. We describe a case of serum sickness in a patient treated with rituximab for mantle cell lymphoma. We also review the literature of rituximab-induced serum sickness.
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PMID:Serum sickness following treatment with rituximab. 1729 33


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