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)

To investigate the role of the complex IgA-alpha-1-antitrypsin (IgA-AT) in systemic lupus erythematosus (SLE) and in mixed connective tissue disease (MCTD), and its possible relations to either activity of the disease or a treatment, we examined a concentration of IgA-AT complex in 65 SLE and 9 MCTD sera. Complex IgA-AT was evaluated using a double antibody enzyme-linked immunoassay (ELISA). Twenty nine patients with SLE (44.6%) and three patients with MCTD (33.3%) had increased serum IgA-AT levels. The mean values of IgA-AT complex in patients with SLE and MCTD were higher than in healthy controls. Among the SLE group, patients with current neurological manifestation were characterized by an increase in IgA-AT serum concentration (2.45 +/- 2.07 U vs. 0.78 +/- 0.70 U, P < 0.001). No relation was found between this complex and ESR level, C-reactive protein (CRP) concentration, or hemoglobin level. Ten SLE patients were treated with CTX intravenously. In this group of patients, IgA-AT complex level was found to be increased compared with patients without such a treatment (1.82 +/- 1.30 U vs. 0.80 +/- 0.67 U, P < 0.05). The present study provides two new observations. Firstly, IgA-AT complex is increased in SLE and MCTD compared with healthy controls, and secondly, patients with CNS involvement displayed a striking increased IgA-AT level.
Lupus 1995 Jun
PMID:IgA-alpha-1-antitrypsin complex in systemic lupus erythematosus: preliminary report. 765 94

Cyclophosphamide (CTX) prevents progression of nephritis and prolongs survival in (NZB x NZW)F(1) (B/W) mice and is used to treat humans with lupus nephritis. To compare the efficacy of CTLA4Ig with CTX and determine whether there is an incremental benefit to combining CTLA4Ig with CTX, we treated B/W mice with CTX, CTLA4Ig, or both agents. In mice with mild renal disease, treatment delayed the onset of proteinuria and prolonged survival in all groups. In mice with advanced renal disease, treatment with both agents reduced proteinuria in 71% of mice, whereas mice treated with either agent alone had no such improvement. Survival was also markedly improved among mice treated with both agents. Thus, combination treatment with CTX and CTLA4Ig is more effective than either agent alone in reducing renal disease and prolonging survival of B/W mice with advanced nephritis. This striking reversal of proteinuria is unprecedented in animal models of SLE.
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PMID:Cutting edge: reversal of murine lupus nephritis with CTLA4Ig and cyclophosphamide. 1120 38

We used the transplantation of purified autologous peripheral blood CD34+ stem cells to treat a 16-year-old female patient with systemic lupus erythematosus (SLE), who had received unsuccessful treatment with steroids and immunosuppressants, and has achieved satisfactory therapeutic effect. The diagnosis of SLE was established one year ago, and the patient had SLE Disease Activity Index (SLEDAI) of 21 on admission. After ineffective treatment with dexamethasone and cyclophosphamid (CTX) for 3 months, purified autologous peripheral blood CD34+ stem cell transplantation was adopted. Autologous peripheral hematopoietic stem cells were mobilized by intravenous injection of 2.0 g/d cyclophosphamid (CTX) for 3 d and subcutaneous injection of granulocyte colony-stimulating factor (G-CSF, 300 microgram/d). A CS-3000 plus blood cell separator was used to collect peripheral blood stem cells, and cell count of mononuclear cells and CD34+ stem cells and epitope analysis of T and B lymphocytes were performed by FACscan flow cytometry. After purification with CliniMACS, the number of CD34+ stem cells reached 15.13x106/kg, while that of CD3+ cells were only 1.35x105/kg. Pretreatment of the patient consisted of intravenous injection of (50 mg/kg each day)for 4 consecutive days and antithymocyte globulin (ATG, 2.5 mg/kg each day) for 3 consecutive days with methylprednisolone (MP) at the dose of 1.0 g on the first day and 0.5 g on the following 2 days. The granulocytes were recovered by G-CSF stimulation. The purified CD34+ stem cells (60 ml) were reinfused within 24 h after pretreatment, following which changes in clinical manifestations and immunologic markers were compared with those before the transplantation. Clinical and immunologic remissions were achieved after transplantation, with all the autoantibodies reversed to the negative, suggesting the short-term effectiveness of this therapy. Based on this observation, we conclude that this therapy is possible to effect an eventual cure of SLE in this case, but the long-term effect needs to be further observed in the follow-up study.
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PMID:[Transplantation of purified CD34+ stem cells from autologous peripheral blood for treatment of systemic lupus erythematosus]. 1243 52

There is accumulating evidence that mycophenolate mofetil (MMF), when combined with corticosteroid, is an effective induction treatment for severe proliferative lupus nephritis and is associated with fewer adverse effects compared to cyclophosphamide (CTX), but the quality of life (QOL) associated with these regimens as perceived by the patient has not been compared. This study included patients who had experienced both treatment regimens, for distinct episodes of diffuse proliferative lupus nephritis. QOL parameters during the first six months of each treatment were assessed through SF36 and WHOQOL questionnaires. Twelve patients and 24 episodes of severe lupus nephritis were studied. CTX-treated and MMF-treated episodes showed comparable baseline characteristics and response rate, with complete remission occurring in 83.3%. MMF treatment was associated with higher numerical scores for all domains across both QOL instruments than CTX. MMF treatment was associated with significantly less fatigue, less impediment of physical and social functioning, and better psychological well being compared to CTX. When each patient served as her/his own control, most patients ascribed higher QOL domain scores to the MMF-treated episode. Seventy-five percent of patients found MMF treatment more acceptable and preferred when compared with CTX, and the complications that most concerned them included Cushingoid features, alopecia, menstrual disturbance and infections. These data showed that MMF-based induction immunosuppression for severe lupus nephritis was associated with better QOL than CTX as perceived by patients, which was most likely attributed to the reduced side-effects during MMF treatment.
Lupus 2006
PMID:Quality of life comparison between corticosteroid- and-mycofenolate mofetil and corticosteroid- and-oral cyclophosphamide in the treatment of severe lupus nephritis. 1683 Aug 84

The presence of renal noninflammatory necrotizing vasculopathy (NNV) is often associated with a severe form of lupus nephritis (LN), which is unresponsive to standard therapy. We conducted a 6-month randomized, prospective, open-label trial comparing mycophenolate mofetil (MMF) (1.5-2.0 g/day) with monthly i.v. cyclophosphamide (CTX) (0.75-1.0 g/m2) as induction therapy for class IV LN with NNV. The primary and second end points were complete remission (CR) and partial remission (PR), respectively. Of 20 patients recruited, nine were randomly assigned to MMF and 11 to CTX. The baseline characteristics between groups were not significant. CR was achieved in four patients (44.4%) receiving MMF and in none of the patients receiving CTX (P = 0.026). PR was achieved in two patients (22.2%) in the MMF group and three patients (27.2%) in the CTX group. The total remission rate (CR + PR) in the MMF and CTX group was 66.6 and 27.2%, respectively (P = 0.17). MMF was more effective than i.v. CTX in reducing proteinuria and haematuria. Adverse events were significantly less frequent with MMF than with CTX (P = 0.028). MMF was superior to i.v. CTX in inducing CR of LN with NNV and had a more favourable safety profile.
Lupus 2007
PMID:Induction therapies for class IV lupus nephritis with non-inflammatory necrotizing vasculopathy: mycophenolate mofetil or intravenous cyclophosphamide. 1772 63

To assess clinical characteristics, pathological findings, and therapeutic response in children with lupus nephritis (LN), we retrospectively studied 25 children under 16 years of age with LN at the Abozar children's hospital from 1995 to 2006. The study included 13(65%) girls and 7(35%) boys. The mean age at the time of diagnosis of SLE was 10.2 (+/- 4.8) years. Eighteen patients (90%) were more than 8 years old. Sixty percent of the patients presented as nephritic-nephrotic syndrome. All the patients underwent percutaneous renal biopsy and were followed up for at least 36 months. The clinical and serologic parameters at the time of renal biopsy were recorded. Twenty patients were treated with the following regimens: one (class I) with low dose prednisone, 7 (class II, III) with high-dose of prednisone, 12 (class IV) with high-dose prednisone plus 13 intermittent intravenous cyclophosphamide (CTX) pulses (monthly for 6 months and then every 3 months), followed by mycophenolate mofetil (MMF) as maintenance therapy. Remission was achieved in 17 (85%) cases; one required hemodialysis and 2 died due to renal failure and central nervous system involvement. Among 12 cases with class IV, 11 responded to prednisone and intravenous CTX pulses. We conclude that i.v. pulses of CTX induced clinical remission of renal disease in the majority of children with severe LN. MMF maintenance therapy was effective after induction of remission in refractory cases. However, this study was performed in a small number of subjects, further studies to confirm the long-term efficacy and safety of CTX pulse therapy on larger numbers of patients are warranted.
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PMID:A clinicopathological study of lupus nephritis in children. 1871 Dec 91

Recent evidence indicates that mesenchymal stem cells (MSC) possess immunosuppressive properties both in vitro and in vivo. We previously demonstrated the functional abnormality of bone marrow derived MSC in patients with systemic lupus erythematosus (SLE). In this study, we aimed to investigate whether transplantation of human bone marrow derived MSC affects the autoimmune pathogenesis in MRL/lpr mice. We found that human MSC from healthy donors reduced the proliferation of T lymphocytes from MRL/lpr mice in a dose-dependent fashion. Two weeks after in vivo transfer of MSC, we detected significantly reduced serum levels of anti ds-DNA antibodies and 24 hour proteinuria in MRL/lpr mice as compared with control groups without MSC transplantation. Moreover, flow cytometric analysis revealed markedly reduced number of CD4(+) T cells while increased Th1 subpopulation in MSC group and MSC + CTX group when compared with controls. Histopathological examination showed significantly reduced renal pathology in MSC-treated mice. Immunohistochemical studies further revealed reduced expression of TGF-beta, FN, VEGF and the deposition of complement C3 in renal tissue after MSC and MSC + CTX treatment. Taken together, we have demonstrated that transplantation of human MSC can significantly inhibit the autoimmune progression in MRL/lpr mice.
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PMID:Transplantation of human bone marrow mesenchymal stem cell ameliorates the autoimmune pathogenesis in MRL/lpr mice. 1911 7

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that, despite the advances in immunosuppressive medical therapies, remains potentially fatal in some patients, especially in treatment-refractory patients. Here, we reported that impairment of bone marrow mesenchymal stem cells (BMMSCs) and their associated osteoblastic niche deficiency contribute in part to the pathogenesis of SLE-like disease in MRL/lpr mice. Interestingly, allogenic BMMSC transplantation (MSCT) is capable of reconstructing the bone marrow osteoblastic niche and more effectively reverses multiorgan dysfunction when compared with medical immunosuppression with cyclophosphamide (CTX). At the cellular level, MSCT, not CTX treatment, was capable to induce osteoblastic niche reconstruction, possibly contributing to the recovery of regulatory T-cells and reestablishment of the immune homeostasis. On the basis of the promising clinical outcomes in SLE mice, we treated four CTX/glucocorticoid treatment-refractory SLE patients using allogenic MSCT and showed a stable 12-18 months disease remission in all treated patients. The patients benefited an amelioration of disease activity, improvement in serologic markers and renal function. These early evidences suggest that allogenic MSCT may be a feasible and safe salvage therapy in refractory SLE patients.
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PMID:Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans. 1948 3

Recent evidence indicates that artesunate has immunomodulatory properties that might be useful for treating autoimmune disease. In this study, we conducted a pilot study and explored the effect and mechanism of artesunate on the treatment of systemic lupus erythematosus using an MRL/lpr murine model. MRL/lpr mice were divided into control, cyclophosphamide (CTX) and artesunate treatment groups. Blood was collected to measure serum levels of creatinine, antinuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA) antibody. Twenty-four-hour urine was collected to measure levels of proteinuria. The concentration of monocyte chemotactic protein-1 (MCP-1) in serum and urine was measured. The expression of MCP-1 in kidney was detected by Western blot and immunohistochemistry assay, respectively. The expression of B cell activating factor (BAFF) in spleen was determined by real time-PCR and immunoblotting. We found that artesunate significantly increased the survival rate, body weight and blood leukocyte counts, and reduced the serum levels of ANA and anti-dsDNA antibody titer, 24 h urinary protein, and serum creatinine. Our results indicated that artesunate could decrease MCP-1, major pro-inflammation cytokine, in serum, urine and kidney. We also found that the level of BAFF, the major B cell activation factor, was decreased in artesunate treated MRL/lpr mice. Its efficacy was comparable with that of CTX in this study. Taken together, we have demonstrated that artesunate can inhibit the progression of disease and reverse the pathologic lesion of lupus nephritis.
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PMID:A pilot study of the therapeutic efficacy and mechanism of artesunate in the MRL/lpr murine model of systemic lupus erythematosus. 2000 22

Various renal vascular lesions are complicated with systemic lupus erythematosus (SLE), and are often overlooked in the actual renal biopsy specimen. We report a case of biopsy-proven lupus vasculopathy, with lupus nephritis class IV-G (A). She developed SLE at 15 years of age, and was treated with prednisolone(PSL) and cyclophosphamide (CTX). Sometimes she experienced a flare-up clinically or serologically, requiring a dose increase of oral PSL. At 40 years of age, she visited our hospital after discontinuation of hospital visits for about 4 months. Oral PSL at 30 mg per day was not effective for urinary abnormalities, increase of anti double-stranded DNA (ds-DNA) antibody titer and decrease in complement components. On admission she had hypertension (180/92 mmHg) and signs of microangiopathic hemolytic anemia. Renal biopsy findings showed the glomerular changes of lupus nephritis, WHO class IV-G (A), and lupus vasculopathy, which is marked luminal narrowing or total occlusion by abundant subendothelial accumulation of immunoglobulins and complement components. In addition to PSL, intravenous pulse CTX promptly achieved clinical remission. When lupus vasculopathy is complicated, CTX may be useful.
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PMID:[Case of lupus vasculopathy associated with lupus nephritis class IV-G (A)]. 2041 36


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