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)

Autologous stem cell transplantation (ASCT) has been proposed as a possible treatment for severe autoimmune diseases such as rheumatoid arthritis (RA), multiple sclerosis (MS), systemic sclerosis, and systemic lupus erythematosus (SLE). To date, more than 250 patients with various autoimmune disorders have undergone an ASCT since 1996. Among them, there is a very limited number of children. This review summarizes the experience with ASCT for pediatric rheumatic diseases. Most reported cases concern juvenile idiopathic arthritis (JIA). Experience with ASCT for childhood SLE, Scleroderma, or Dermatomyositis is very limited. To date, 12 children with severe systemic or polyarticular JIA, all with progressive disease activity despite the use of corticosteroids, MTX, CsA, or Cyclophosphamide were treated in our center with ASCT. Rheumatologic follow-up at 3-month intervals up to 36 months showed a marked decrease in arthritis severity as expressed by the core-set criteria for juvenile chronic arthritis (JCA) activity. However, these children remain at risk for severe viral infections due to the prolonged lymfopenia. ASCT in this severely ill patient group induces a very significant and drug-free remission of the disease, but carries a significantly risk of developing fatal MAS.
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PMID:Autologous hemopoietic stem-cell transplantation for children with refractory autoimmune disease. 1112 77

A minority of children suffering from severe rheumatic diseases are unresponsive to conventional treatments. These patients can now be managed with a variety of immunosuppressive therapies. Methotrexate is considered the first choice disease-modifying agent for adult and juvenile rheumatoid arthritis. In patients unresponsive to low doses of methotrexate, medium or high-doses can be useful. Instead of methotrexate, a recently developed immunosuppressive drug, mycophenolate-mofetil, which inhibits T- and B-lymphocyte proliferation, can be used. Another possibility for refractory rheumatic diseases, with no increase in toxicity, is combination therapy, for example methotrexate plus cyclosporine, or methotrexate plus salazopyrine or intravenous pulses of cyclophosphamide and methylprednisone. More recently two distinct inhibitors of tumor necrosis factor (etanercept and infliximab have been used successfully for intractable rheumatic diseases (juvenile idiopathic arthritis, psoriatic arthritis, spondyloarthropathies) but the follow-up is still too short to establish their long-term effectiveness. If all these treatments are unsuccessful, an autologous bone marrow transplantation can be proposed to selected patients. Interesting results have been obtained in pediatric rheumatic diseases such as juvenile idiopathic arthritis, systemic lupus erythematosus and systemic sclerosis. Further studies are required to assess the best procedures able to induce remission with a minimal risk of fatal events.
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PMID:Autologous bone marrow transplantation versus alternative drugs in pediatric rheumatic diseases. 1126 32

Methotrexate is beneficial in rheumatoid arthritis and has been used in small studies of patients with systemic lupus erythematosus. We describe a patient with severe subacute cutaneous lupus erythematosus refractory to therapy with antimalarials and corticosteroids. Treatment with methotrexate resulted in complete clearing of the skin lesions without any side effects.
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PMID:Methotrexate treatment for refractory subacute cutaneous lupus erythematosus. 1190 17

Our experience regarding serum soluble interleukin-2 receptor (sIL-2R) measurement as a marker of lymphocyte activation consists of patients with autoimmune disease: 37 with systemic lupus erythematosus (SLE), 23 with autoimmune hepatitis (AIH), 74 with inflammatory bowel disease and six with Wegener's granulomatosis (WG). The influence of immunosuppressive therapy has also been assessed. Serum sIL-2R in SLE is significantly higher than in healthy controls and good correlation is found between sIL-2R and disease activity. Severity of kidney inflammation in lupus nephritis can be reflected by the increased excretion of sIL-2R. It was found that sIL-2R level significantly falls when the disease becomes clinically inactive after immunosuppressive therapy, but in many cases (up to 50%) it does not reach normal levels. The last finding suggests that lymphocyte activation may still be present even though the disease is considered inactive under clinical criteria and support the need of prolonged immunosuppression after the first signs of remission. In AIH the serum levels of sIL-2R are elevated in all patients with active disease; all cases with "highly active" disease have significantly higher concentrations than patients with "mild activity". A good correlation has been demonstrated between elevated serum sIL-2R values and anti-asialoglycoprotein receptor (ASGPR) titer (the specific marker of AIH). The follow-up study showed a significant decrease of both sIL-2R levels and anti-ASGPR titer after 3-9 month immunosuppressive therapy. The findings support that sIL-2R and anti-ASGPR titer could serve as reliable humoral markers for disease-specific activity. Compared with inactive ulcerative colitis (UC) and Crohn's disease (CD), significantly higher levels of sIL-2R were present in the serum of patients with active disease, and in inactive disease than in healthy age-matched controls. Methotrexate (MTX) therapy of patients with refractory UC resulted in sIL-2R decrease at the end of therapeutic period (20 i.m. injections of once a week 25 mg), good responders showing > 50% decrease even at 5-7 weeks of treatment. Serum sIL-2R is elevated in all six patients with WG. Contrary to anti-neutrophil cytoplasmic antibodies (ANCA), sIL-2R remains elevated above cut-off for normal range, despite clinical improvement following immunosuppressive treatment. The last observation suggests that serum sIL-2R is not a good measure of the disease activity and argue for the need of longer immunosuppressive therapy just after the first days of clinical remission.
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PMID:Serum soluble IL-2 receptor as a marker of lymphocyte activation in some autoimmune diseases. Effect of immunosuppressive therapy. 1216 73

Ideally, immunosuppressive drugs would not be necessary in pregnancy. However, in connective tissue disease (especially systemic lupus erythematosus, SLE) vasculitis, and sometimes antiphospholipid antibody syndrome, their use is necessary both to protect the health of the mother and to insure the success of the pregnancy. The more commonly used drugs will be reviewed, with an emphasis on human data, when available. Methotrexate and leflunamide will not be considered, for they should never be used in pregnancy.
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PMID:Immunosuppressive drug use in pregnancy. 1276 71

Systemic lupus erythematosus (SLE) is an autoimmune disease manifested by multi-organ involvement and elevated titers of anti-DNA antibodies. Current therapies for SLE are broadspectrum, and include steroids and immunosuppressive cytotoxic agents that are counterbalanced by the toxicity and side effects of the medications. One of the goals is to target therapies by altering specific known mechanisms of inflammation and autoimmunity. Although the inciting antigen is still unknown in SLE, it may be possible to alter the regulation of the immune response by targeted molecular therapy. Methods under investigation, which may be beneficial, are manipulation of second-signal stimulation of the immune response (anti-CD40L), manipulation of cytokines (monoclonal anti-IL-10), inducing tolerance by administration of blocking peptides (LJP394), and the manipulation of idiotypes (IVIg). In this article, we also discuss modalities that are steroid-sparing (MTX), and selective immunosuppression (stem-cell restoration and MMF). We review the ongoing literature from 2000-2002, utilizing the MEDLINE search. Controlled trials, open trials, and trials in phase I and II have been included, and anecdotal reports were excluded. The major advances have been with mycophenolate mofetil (MMF) and LJP 394.
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PMID:Novel Approaches to Therapy for SLE. 1279 65

Methotrexate (MTX) is one of the immunosuppressory compounds applied in the prophylaxis and treatment of several diseases, including: rheumatoid arthritis, systemic lupus erythematosus, psoriasis, graft-versus-host disease and, in combination with other drugs, neoplastic diseases. Studies in humans and in animal model, of clinical disease, have demonstrated that MTX diminishes the clinical symptoms of various immunological disorders. MTX, an antagonist of folic acid synthesis, causes apoptosis in activated cells, primarily in the G1 and S phases of the cell cycle. One of its actions, is inhibition of the synthesis or activity of several proinflammatory cytokines. At high doses, MTX is cytotoxic to hemopoietic cells; low doses, however, promote hemopoiesis. MTX also induces the differentiation of monocytic tumor cells, which may explain, in part, its therapeutic effects in the treatment of some disorders. The compound suppresses both cellular and humoral immune response and mitogen-induced lymphocyte proliferation. These effects are dose- and time-dependent. The strongest suppressory activity is exerted when MTX is applied 24 or 48 hours after immunization or mitogen stimulation. Administration of MTX in unfavorable conditions such as stress or other diseases, diminishes its tolerance and increases its toxicity. Side-effects of MTX may be ameliorated by application of pharmacological synthetic agents and plant extracts. In summary, MTX has been an effective agent in suppressing immunological disorders (for 50 years) and is still finding many applications.
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PMID:[Effect of methotrexate on the immune response in selected experimental models]. 1511 58

The gold standard for inducing remission in systemic necrotizing vasculitis (SNV) and severe lupus nephritis is (and remains) the combination of cyclophosphamide and glucocorticoids. Long-term treatment with cyclophosphamide is limited because of toxicity. Recent prospective studies in antineutrophil cytoplasmic antibody (ANCA)-associated SNV revealed that after achievement of clinical remission (usually within 3-4 months after starting cyclophosphamide) cyclophosphamide can be replaced by azathioprine with no increase in relapse rates if treatment is continued for at least 1 year. Methotrexate is inferior to cyclophosphamide because of increased relapse rates-particularly in those with renal involvement-during follow-up. An ongoing study comparing mycophenolate mofetil (MMF) with azathioprine will clarify whether MMF is as successful as azathioprine or even better. The concomitant use of tumor necrosis factor (TNF)-alpha blockers increases the efficacy of immunosuppression. TNF-alpha blockers may be added if SNV is refractory to standard immunosuppressive therapy. However, with this addition to therapy, systemic infections are more frequent. In patients with severe lupus nephritis (WHO IV) the efficacy of combined i.v. therapy with cyclophosphamide and glucocorticoids was shown by NIH trials. This NIH regimen competes with the EURO-Lupus nephritis schedule with a lower dose of i.v. cyclophosphamide followed by maintenance therapy with azathioprine. Long-term follow-up is, however, still lacking in the EURO-Lupus trial. Ongoing prospective studies will reveal whether cyclophosphamide may be substituted by MMF from the very beginning or whether MMF is superior to azathioprine during maintenance therapy of lupus nephritis.
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PMID:Cyclophosphamide treatment in systemic necrotizing vasculitis and lupus nephritis. How long? How much? 1525 54

Methotrexate (MTX) and mycophenolic acid (MPA) are used in the clinic for their immunosuppressive properties. MTX is widely used for the treatment of rheumatoid arthritis (RA). MPA is used to prevent graft rejection and is now experimentally used in systemic lupus erythematosis and RA. It is known that both drugs interfere with DNA synthesis. However, the precise mechanism of action is still debated. We have analysed the effect of the drugs on cytokine production in whole blood during short cultures. The production of T-cell cytokines was inhibited by both drugs. MTX inhibits cytokine production because MTX induces apoptosis in activated T-cells. MPA inhibits cytokine production by preventing T-cells to progress to the S-phase of the cell cycle. Cytokine production by monocytes was slightly decreased by the drugs. The reason for this inhibition is not clear. These results indicate that T-cells are the main target cells of the immunosuppressive drugs MPA and MTX.
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PMID:Two inhibitors of DNA-synthesis lead to inhibition of cytokine production via a different mechanism. 1557 Dec 8

Homocysteine (Hcy), a sulfur-containing amino acid, is eliminated through B vitamins-dependent pathways. Hyperhomocysteinemia has been found to be an independent risk factor for atherosclerotic cardiovascular, cerebrovascular, and peripheral vascular diseases. Recently, psoriasis, lupus, and rheumatoid arthritis were reported to be associated with hyperhomocysteinemia. This study was aimed to evaluate the changes of plasma Hcy level before and after sulfasalazine and MTX therapy in patients with ankylosing spondylitis (AS). One hundred and two patients with AS and ten normal controls were enrolled in the cross-sectional case-control study. Fasting plasma Hcy levels were determined by ELISA kits (IMX, Abbott). Hcy levels were compared to their Bath AS disease activity index (BASDAI) and the usage of sulfasalazine and/or MTX. Active disease was defined by BASDAI as more than 3 in a 10-cm scale with ESR >20 mm/h. For those patients with plasma Hcy >or=15 micromol/l, a perspective trial of daily supplement of vitamin B-12 0.5 mg, B-6 50 mg, and folic acid 5 mg for 2 weeks were also tested for the efficacy. Plasma Hcy level increased significantly in AS patients under sulfasalazine (10.4+/-3.8 micromol/l, p<0.05), MTX (11.9+/-4.7, p<0.05) and sulfasalazine/MTX combination treatment (11.2+/-2.6, p<0.05) compared with normal controls (8.6+/-1.2 micromol/l) and AS patients without DMARD(9.4+/- 2.6 micromol/l). No correlation between disease activity and plasma Hcy level was found. Daily supplement of vitamin B-12 0.5 mg, B-6 50 mg, and folic acid 5 mg can lower Hcy level in 2 weeks (32.3+/-24.0 vs 15.6+/-11.1 micromol/l, p=0.007). Plasma homocysteine level did significantly increase in AS patients under sulfasalazine or MTX treatment. B-vitamins should be considered as a routine supplementation for patients who underwent sulfasalazine and/or MTX treatment. Further longitudinal studies are required to confirm the conclusions.
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PMID:Plasma homocysteine status in patients with ankylosing spondylitis. 1702 18


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