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)

Innovative approaches are needed for patients with systemic lupus erythematosus (SLE) who develop autoimmune haemolytic anaemia (AIHA) that does not respond to conventional treatment. Rituximab, a chimaeric anti-CD20 monoclonal antibody, has been demonstrated to be highly effective for in vivo B-cell depletion. We report an 18-year-old-girl with SLE and life-threatening AIHA that did not respond to steroids, intravenous immunoglobulin and cyclosporin A. Rituximab was given weekly at 375 mg/m2 for two doses. The drug was well tolerated and the patient had no adverse effects. Her haemolytic disorder markedly ameliorated, with a progressive increase of haemoglobin levels, starting a few days after therapy. The patient remains disease-free 7 months later.
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PMID:Anti-CD20 monoclonal antibody (Rituximab) for life-threatening autoimmune haemolytic anaemia in a patient with systemic lupus erythematosus. 1184 53

There is a growing body of experimental evidence that B lymphocytes play a central role in the pathogenesis of systemic lupus erythematosus (SLE). B cells are, by definition, the precursors of antibody-secreting cells, and thus are the source of pathogenic autoantibodies. However, recent data indicate that B cells are not merely the passive producers of immunoglobulins, but also play a central role in autoimmunity via nonconventional mechanisms, including autoantigen presentation and modulation of other immune cells. Thus, B lymphocyte depletion has recently emerged as a promising therapeutic approach to the treatment of autoimmune diseases, including SLE. Rituximab is a chimeric mouse-human monoclonal antibody against the B cell-specific antigen CD20, which selectively and profoundly depletes B lymphocytes and has been widely used to treat B cell lymphomas. Recent open-label studies indicate that rituximab is safe and may be efficacious in the treatment of SLE, and continued study with randomized clinical trials is justified.
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PMID:B cell depletion therapy in systemic lupus erythematosus. 1296 16

We report a case of hypocomplementemic urticarial vasculitis and recurrent angioedema in a patient with systemic lupus erythematosus unresponsive to mycophenolate mofetil, high-dose methylprednisolone, and intravenous immunoglobulin that responded rapidly to rituximab. Rituximab is a monoclonal antibody against CD20 transmembrane protein on the surface of mature and malignant B cells. No adverse effects occurred during or after therapy, and the patient was discharged from the hospital for outpatient rituximab infusion and follow-up care.
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PMID:Hypocomplementemic urticarial vasculitis with angioedema, a rare presentation of systemic lupus erythematosus: rapid response to rituximab. 1457 55

Systemic lupus erythematosus (SLE) is a chronic, inflammatory autoimmune disease that may involve multiple organ systems. Treatment consists of immunosuppression, cytotoxic treatment, plasmapheresis and immunoglobuline therapy. Treatment of patients refractory to standard treatment approaches is difficult and results are poor. We describe a 39-year old patient with SLE suffering from grand mal epilepsy due to cerebral vasculopathy with positive lupus anticoagulant, who was refractory to standard treatment modalities. The patient was treated with the anti-CD20 monoclonal antibody rituximab (375 mg/m2 x 4, repeated at weekly intervals). Rituximab applications were delivered in October 2000, March 2001 and October 2001. Since March 2002 she has received maintenance therapy with rituximab 375 mg/m2 every three months. A second female with refractory SLE was treated successfully in April 2002 and receives maintenance therapy every three months. Both patients responded well to rituximab therapy. The first patient showed a major improvement of her clinical condition, and 30 months after the beginning of the rituximab therapy she is free of any symptoms. Inflammation parameters, ANA and lupus anticoagulant declined significantly after the treatment. The clinical condition of the second patient improved dramatically, all inflammation parameters normalized and her circulating immunocomplexes disappeared. In conclusion, rituximab maintenance treatment may be a new effective therapy in SLE.
Lupus 2003
PMID:Successful long-term treatment of systemic lupus erythematosus with rituximab maintenance therapy. 1459 28

Rituximab (Rituxan) is a human-mouse chimeric monoclonal antibody that targets the B-cell CD20 antigen and causes rapid and specific B-cell depletion. Rituximab was approved in the United States in 1997 to treat low-grade or follicular, relapsed or refractory, CD20-positive B-cell non-Hodgkin's lymphoma (NHL). Since then, further clinical experience with rituximab has been incorporated into the prescribing information, which now stipulates an extended eight-week schedule, treatment of patients with refractory or relapsed bulky disease measuring >10 cm, and retreatment of patients who responded to rituximab previously. In 1998, the European Union approved rituximab (MabThera) to treat stage III/IV, follicular, chemotherapy-resistant, or relapsed NHL. Recently, the European Union also approved the use of rituximab in combination with standard chemotherapy for aggressive NHL. Many clinical trials have evaluated rituximab, alone or with other therapies, in indolent and aggressive NHL as well as other B-cell lymphoproliferative disorders. New studies are evaluating rituximab's role in first-line therapy, maintenance therapy, and stem-cell transplantation procedures. The use of rituximab against autoimmune disorders, such as rheumatoid arthritis, immune thrombocytopenic purpura, autoimmune hemolytic anemia, systemic lupus erythematosus, and multiple sclerosis, is also under investigation.
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PMID:Rituximab: expanding role in therapy for lymphomas and autoimmune diseases. 1474 32

Standard treatment for autoimmune hemolytic anemia (AIHA) due to warm antibodies includes combinations of glucocorticoids, immunosuppressive drugs (mainly azathioprine) and splenectomy. Patients who are refractory or intolerant to these therapies constitute an important therapeutic challenge. Rituximab, an anti-CD20 chimeric monoclonal antibody, can effectively deplete B-cells and is commonly used in B-cell non-Hodgkin lymphoma. In addition, it is being increasingly used in autoimmune disorders, such as idiopathic thrombocytopenic purpura, AIHA, systemic lupus erythematosus or vasculitis. We report a case of warm AIHA associated to primary antiphospholipid syndrome (APS). The patient was refractory to high-dose corticosteroids. Splenectomy was discarded in view of the high risk of thrombotic and/or hemorrhagic perioperative complications, due to the presence of APS. After treatment with four weekly doses of rituximab the patients had a rapid and sustained response which allowed progressive tapering of prednisone dose to 5 mg/d. In addition, IgM anticardiolipin titres decreased from > 600 MPL to < 100 MPL. Thirteen further cases of warm AIHA in adults treated with rituximab have been reviewed, showing excellent tolerance and high response rates. Rituximab may be considered prior to splenectomy in patients with refractory AIHA and high risk of complications following splenectomy.
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PMID:Sustained response to rituximab of autoimmune hemolytic anemia associated with antiphospholipid syndrome. 1537 86

CD20 is a 33-37 kDa, non-glycosylated phosphoprotein expressed on the surface of almost all normal and malignant B cells. It is also the target for rituximab, the most effective anti-cancer monoclonal antibody developed to date. Rituximab has now been given to over 300,000 lymphoma patients in the last decade and interestingly is now being explored for use in other disorders, such as autoimmune conditions including rheumatoid arthritis and systemic lupus erythematosus. Despite the success in immunotherapy, knowledge about the biology of CD20 is still relatively scarce, partly because it has no known natural ligand and CD20 knockout mice display an almost normal phenotype. However, interesting insight has come from work showing that CD20 is resident in lipid raft domains of the plasma membrane where it probably functions as a store-operated calcium channel following ligation of the B cell receptor for antigen. In the current review, these and data relating to its activity as a therapeutic target will be discussed in depth. It is clear that a greater understanding of CD20 biology and the effector mechanisms, such as antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and growth regulation, which operate with anti-CD20 mAb in vivo will allow more efficient exploitation of CD20 as a therapeutic target.
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PMID:The biology of CD20 and its potential as a target for mAb therapy. 1556 20

Rituximab, a chimeric monoclonal CD20 antibody, is useful in the treatment of B-cell lymphomas and certain autoimmune diseases. We report a successful outcome of rituximab for life threatening hypercoagulable state associated with lupus anticoagulant (LA). A 30-year-old woman initially presented 10 years ago with DVT and positive serology for SLE and LA. While on Coumadin, she suffered from recurrent DVT in the legs and arms, pulmonary emboli, Budd-Chiari syndrome, mesenteric vein thrombosis, bone infarcts, recurrent strokes, and chronic ITP. All measures including plasmapheresis and monthly IV cyclophosphamide were of no benefit. She was recently admitted with spontaneous subdural hematoma with INR of 3.8. Upon discontinuation of anticoagulation for surgical drainage, she developed acute abdomen from thrombosis and recurrent DVT. Because she had failed prior standard measures, 4 weekly infusions of rituximab (375 mg/m2) were given following 2 rounds of plasmapheresis. Subsequently, she made a remarkable recovery over the next month and has been free of thrombosis on Coumadin for over 15 months. LA, IgM antibodies to cardiolipin, and B2GP1 were consistently positive. After rituximab therapy, LA became negative and IgM antibodies to cardiolipin decreased and ITP went into remission. Rituximab induced a lasting remission in a woman suffering from life-threatening hypercoagulable state associated with LA. Her clinical remission was associated with disappearance of LA.
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PMID:Long-term remission from life-threatening hypercoagulable state associated with lupus anticoagulant (LA) following rituximab therapy. 1568 9

Rituximab, a chimeric monoclonal antibody specific for human CD20, has recently been used for the treatment of autoimmune diseases. A 14-year-old patient with severe systemic lupus erythematosus (SLE) and class IV glomerulonephritis presented with immunologic and clinical resistance to conventional immunosuppressive therapy for 10 months after diagnosis. To induce remission of active SLE, treatment with 6 monthly rituximab at 375 mg/m(2), oral mycophenolate and prednisone was initiated followed by maintenance rituximab every 3 months. The SLEDAI decreased significantly from 31 at diagnosis to 14 after nine applications of rituximab. Extrarenal symptoms of SLE improved significantly. However, after induction therapy with rituximab the patient presented a reversible intrinsic acute renal insufficiency for a period of 3 weeks. The discontinuation of the daily medication (oral prednisone and mycophenolate) by the patient herself may explain the progression of active SLE associated with the reversible acute renal failure. Under intensive immunosuppressive therapy improvement of active disease manifestations and stabilization of plasma creatinine concentrations to normal values was observed. However, proteinuria remained elevated and improved only after a protracted period (median protein-to-creatinine ratio 5.2 g/g, range 0.8-11.2 g/g). Hematuria and urinary cell casts persisted. In conclusion, the extrarenal symptoms of the patient responded particularly well to rituximab. However, despite complete B-cell elimination, renal remission of SLE was not achieved. Thus, it may be possible that humoral and cellular immune mechanisms have a fundamental involvement in the pathogenesis of SLE nephritis.
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PMID:Rituximab in childhood systemic lupus erythematosus refractory to conventional immunosuppression: case report. 1650 74

The use of B cell depletion as a mode of treatment for non-Hodgkin's lymphoma was first utilized in 1997 when Rituximab, a chimeric human-mouse monoclonal antibody which has a high affinity to the CD20 antigen expressed on B cells, became available. Over 500000 lymphoma patients have been treated worldwide with this drug and it has a good safety record. The notion that B cells might be critical to the development of rheumatoid arthritis led to the extension of the use of B cell depletion to this condition and a recent double blind controlled trial has shown very encouraging results. In addition, B cell depletion either using Rituximab alone, or in combination with cyclophosphamide and corticosteroids has also been reported to have been of great benefit in some patients with severe systemic lupus erythematosus albeit in open label studies. This review considers the mechanism of action of the drug, the clinical trials that have been reported, and tries to place its current use in patients with autoimmune rheumatic disease in context.
Lupus 2005
PMID:Anti-B cell therapy (rituximab) in the treatment of autoimmune diseases. 1580 98


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