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)

Nine patients with SLE-associated neutropenia and infections received 48 Mio U G-CSF per day s.c. for 2-17 days as an adjunct to antibiotic treatment. Granulopoiesis was normal or hyperplastic in all cases. The mean granulocyte count increased within 2 days from 1.4 per nl to 11.4 per nl. Side-effects were exacerbating CNS symptoms in two patients and a case of leukocytoclastic vasculitis. G-CSF induced constantly a rapid and distinct increase of neutrophil granulocytes in lupus-associated neutropenia patients with normo- or hyperplastic granulopoiesis.
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PMID:[G-CSF in patients with lupus-associated neutropenia and infections]. 876 47

The hematologic manifestations of HIV infection and AIDS are common and may cause symptoms that are life-threatening and impair the quality of life of these patients. The most important of these manifestations are cytopenias. Anemia and neutropenia are generally caused by inadequate production because of suppression of the bone marrow by the HIV infection through abnormal cytokine expression and alteration of the bone marrow microenvironment. Thrombocytopenia is caused by immune-mediated destruction of the platelets, in addition to inadequate platelet production. The incidence and severity of cytopenia are generally correlated to the stage of the HIV infection. Other causes of cytopenia in these patients include adverse effects of drug therapy, the secondary effects of opportunistic infections or malignancies, or other preexisting or coexisting medical problems that may be prevalent in the HIV-infected population. Diagnosis of the mechanism and cause of the cytopenia may allow for specific management. Optimal management of the underlying HIV infection is essential, and mild cytopenia in asymptomatic patients may need no specific management. Supportive care for anemia includes the use of erythropoietin in addition to the judicious use of red blood cell transfusions. Therapy for neutropenia includes the use of the myeloid growth factors G-CSF and GM-CSF. Immune-mediated thrombocytopenia may be treated with a combination of zidovudine, corticosteroids, IVGG, and splenectomy. Platelet transfusions are sometimes needed for the treatment of thrombocytopenia caused by decreased production. Other hematologic manifestations such as hypergammaglobulinemia and lupus anticoagulants are commonly asymptomatic and usually require no specific therapy, but they can rarely cause morbidity and require specific interventions.
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PMID:Hematologic complications of human immunodeficiency virus infection and the acquired immunodeficiency syndrome. 909 37

A 46 year woman with severe long-lasting SLE received an autologous bone marrow transplantation utilising CD34+ haematopoietic progenitors following a 3log T-lymphocyte depletion. The immunosuppressive regimen (conditioning) consisted of 15mg/kg Thiotepa followed by 100 mg/kg of cyclophosphamide over 2d. Granulocytic recovery was aided by G-CSF. The post-transplant course was uneventful, and a good clinical and immunologic remission (ANA negativisation) was achieved. This is the first case of SLE having received an autologous progenitor cell transplant for the autoimmune disease by itself, unaccompanied by a haematologic condition requiring transplantation. The potential, advantages and limits of this procedure, which are currently being explored worldwide, are briefly discussed.
Lupus 1997
PMID:Autologous marrow stem cell transplantation for severe systemic lupus erythematosus of long duration. 925 15

G-CSF not only functions as an endogenous hemopoietic growth factor for neutrophils, but also displays pro-Th2 and antiinflammatory properties that could be of therapeutic benefit in autoimmune settings. We evaluated the effect of treatment with G-CSF in a murine model of spontaneous systemic lupus erythematosus, a disease in which G-CSF is already administered to patients to alleviate neutropenia, a common complication. Chronic treatment of lupus-prone MRL-lpr/lpr mice with low doses (10 microg/kg) of recombinant human G-CSF, despite the induction of a shift toward the Th2 phenotype of the autoimmune response, increased glomerular deposition of Igs and accelerated lupus disease. Conversely, high-dose (200 microg/kg) treatment with G-CSF induced substantial protection, prolonging survival by >2 mo. In the animals treated with these high doses of G-CSF, neither the Th1/Th2 profile nor the serum levels of TNF-alpha and IL-10 were modified. Despite the presence of immune complexes in their kidney glomeruli, no inflammation ensued, and serum IL-12 and soluble TNF receptors remained at pre-disease levels. This uncoupling of immune complex deposition and kidney damage resulted from a local down-modulation of FcgammaRIII (CD16) expression within the glomeruli by G-CSF. Our results demonstrate a beneficial effect of high doses of G-CSF in the prevention of lupus nephritis that may hold promise for future clinical applications, provided caution is taken in dose adjustment.
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PMID:Granulocyte-colony stimulating factor treatment of lupus autoimmune disease in MRL-lpr/lpr mice. 1052 19

Internationally 397 patients (310 in Europe/Austalasia and 87 in North America) with severe autoimmune disease (AD) have received an autologous haemopoietic stem cell transplant (HSCT) following immunoablation, 32 with systemic lupus erythematosus (SLE). The 23 in the EBMT/EULAR database mostly received cyclophosphamide (Cy) and G-CSF as mobilisation followed by Cy and antithymocyte globulin (ATG) conditioning. Nineteen improved with five relapses (mostly mild to moderate) and there were three procedure-related mortalities. In the Chicago series, nine patients were entered, seven improved, one died following mobilisation and one from active disease 3 months after mobilisation. Randomised, prospective controlled phase III trials are desired, but by consensus, more phase I and II data is required to plan the optimal protocol.
Lupus 2001
PMID:Immunoablation and haemopoietic stem cell transplantation for severe autoimmune disease with special reference to systemic lupus erythematosus. 1131 55

We reviewed data from 24 transplant centers in Asia, Australia, Europe, and North America to determine the outcomes of stem cell collection including methods used, cell yields, effects on disease activity, and complications in patients with autoimmune diseases. Twenty-one unprimed bone marrow harvests and 174 peripheral blood stem cell mobilizations were performed on 187 patients. Disease indications were multiple sclerosis (76 patients), rheumatoid arthritis (37 patients), scleroderma (26 patients), systemic lupus erythematosus (19 patients), juvenile chronic arthritis (13 patients), idiopathic autoimmune thrombocytopenia (8 patients), Behcet's disease (3 patients), undifferentiated vasculitis (3 patients), polychondritis (1 patient) and polymyositis (1 patient). Bone marrow harvests were used in the Peoples Republic of China and preferred worldwide for children. PBSC mobilization was the preferred technique for adult stem cell collection in America, Australia, and Europe. Methods of PBSC mobilization included G-CSF (5, 10, or 16 microg/kg/day) or cyclophosphamide (2 or 4 g/m2) with either G-CSF (5 or 10 microg/kg/day) or GM-CSF (5 microg/kg/day). Bone marrow harvests were without complications and did not affect disease activity. A combination of cyclophosphamide and G-CSF was more likely to ameliorate disease activity than G-CSF alone (P < 0.001). g-csf alone was more likely to cause disease exacerbation than the combination of cyclophosphamide and g-csf (P = 0.003). Three patients died as a result of cyclophosphamide-based stem cell collection (2.6% of patients mobilized with cyclophosphamide). When corrected for patient weight and apheresis volume, progenitor cell yields tended to vary by underlying disease, prior medication history and mobilization regimen. Trends in the approaches to, and results of, progenitor cell mobilization are suggested by this survey. While cytokine-based mobilization appears less toxic, it is more likely to result in disease reactivation. Optimization with regard to cell yields and safety are likely to be disease-specific and prospective disease-specific studies of mobilization procedures appear warranted.
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PMID:Collection of hematopoietic stem cells from patients with autoimmune diseases. 1149 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

In order to understand the effect of hematopoietic stem cell mobilization agents, G-CSF and GM-CSF, on the expression of TNF-alpha mRAN and CD69 and secretion of IgG in SLE patients' peripheral blood mononuclear cells (PBMNC), expression of TNF-alpha mRNA and CD69 was measured by RT-PCR and flow cytometry, respectively, and IgG secretion by ELISA. The results showed that 0.1 - 2.0 microg/ml G-CSF did not affect the expression of TNF-alpha mRNA in active and static patients' PBMNC treated with 0.1 - 2.0 microg/ml cytokines, and 2.0 microg/ml GM-CSF increased the expression of TNF-alpha mRNA in active patients' PBMNC. G-CSF and GM-CSF did not interfere the expression of CD69 in active and static patients' PBMNC, however, the expression of CD69 was significantly increased in active patients' PBMNC treated with GM-CSF at more than 8 microg/ml. There was no obvious change of IgG secretion from PBMNC induced with 10 microg/ml G-CSF, while the IgG secretion was stimulated by 10 microg/ml GM-CSF. It was concluded that G-CSF as a mobilization agent could be safe to SLE patients, but GM-CSF may cause some harmful effects to patients because of the increase of the parameters relating to activity of lupus in active SLE patients.
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PMID:[Effect of G-CSF and GM-CSF on expression of TNF-alpha mRNA and CD69 and secretion of IgG in peripheral blood mononuclear cells from systemic lupus erythematosus patients]. 1251 15

Type 1 interferon-producing cells (IPCs), also known as plasmacytoid dendritic cell (DC) precursors, represent the key effectors in antiviral innate immunity and triggers for adaptive immune responses. IPCs play important roles in the pathogenesis of systemic lupus erythematosus (SLE) and in modulating immune responses after hematopoietic stem cell transplantation. Understanding IPC development from hematopoietic progenitor cells (HPCs) may provide critical information in controlling viral infection, autoimmune SLE, and graft-versus-host disease. FLT3-ligand (FLT3-L) represents a key IPC differentiation factor from HPCs. Although hematopoietic cytokines such as interleukin-3 (IL-3), IL-7, stem cell factor (SCF), macrophage-colony-stimulating factor (M-CSF), and granulocyte M-CSF (GM-CSF) promote the expansion of CD34+ HPCs in FLT3-L culture, they strongly inhibit HPC differentiation into IPCs. Here we show that thrombopoietin (TPO) cooperates with FLT3-L, inducing CD34+ HPCs to undergo a 400-fold expansion in cell numbers and to generate more than 6 x 10(6) IPCs per 10(6) CD34+ HPCs within 30 days in culture. IPCs derived from HPCs in FLT3-L/TPO cultures display blood IPC phenotype and have the capacity to produce large amounts of interferon-alpha (IFN-alpha) and to differentiate into mature DCs. This culture system, combined with the use of adult peripheral blood CD34+ HPCs purified from G-CSF-mobilized donors, permits the generation of more than 10(9) IPCs from a single blood donor.
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PMID:Thrombopoietin cooperates with FLT3-ligand in the generation of plasmacytoid dendritic cell precursors from human hematopoietic progenitors. 1467 Sep 16

Some patients with severe systemic lupus erythematosus do not respond to conventional immunosuppression or suffer severe side effects from such treatment. In order to explore the concept of immunoablation followed by haematopoietic stem cell transplantation (HSCT) or 'rescue', an international collaboration has occurred over the past seven years. The European Group for Blood and Marrow Transplantation (EBMT) and The European League Against Rheumatism (EULAR) have analysed their collective phase I and II studies and found a remission rate (based on a reduction of the SLEDAI to < 3) in 66%, one-third of whom later relapsed to some degree. The most often used protocol was cyclophosphamide (CY) and G-CSF for mobilization and CY plus anti thymocyte globulin as conditioning. Procedure related mortality was 12% in this sick group of patients with major organ involvement. The North American, mostly single centre experience showed higher rates of remission and one procedure related death. Some relapse was also observed. Phase II studies designed to assess the role of post-HSCT maintenance therapy are being considered by the EBMT/EULAR group.
Lupus 2004
PMID:Autologous stem cell transplantation for systemic lupus erythematosus. 1523 Feb 93


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