Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Photopheresis, the process by which peripheral blood is exposed in an extracorporeal flow system to photoactivated 8-methoxypsoralen (8-MOP), is an effective new treatment for certain disorders caused by aberrant T lymphocytes. It has become a standard therapy for advanced cutaneous T cell lymphoma and shows promise in the treatment of four autoimmune disorders (pemphigus vulgaris, the progressive systemic sclerosis form of scleroderma, rheumatoid arthritis, systemic lupus erythematosus) and in reversal of immunologic rejection of transplanted organs. Positive immunologic alterations observed in patients with AIDS-related complex merit further investigation, and preliminary trials in the management of patients with multiple sclerosis, myasthenia gravis and autoimmune insulin-dependent diabetes mellitus have recently been initiated. The inability of the treatment to meaningfully alter the course of the B cell malignancy, chronic lymphocytic leukemia, suggests that B cell proliferations, at least those involving malignant cells, may be more resistant to this treatment. The mechanism of action of photopheresis is likely to be multifaceted, but at least in experimental systems appears to involve an immunization against the pathogenic T cells, in a highly specific manner. Photoactivated 8-MOP initiates a cascade of cellular events by forming covalent photoadducts with nuclear DNA, with cell surface molecules and possibly with other cytoplasmic components of the ultraviolet exposed leukocytes. For reasons not yet clear, exposure of populations of T cells containing expanding a clone(s) of pathogenic T cells to photoactivated 8-MOP alters these cells so that their reinfusion induces a therapeutically significant immunologic reaction that targets unirradiated T cells of the same pathogenic clone(s). It is suggested that the specificity of the induced immunologic reaction may result, in sequence, from the exquisitely titratable damage that 8-MOP inflicts upon cells of the pathogenic clone(s), the return of these cells to an immunocompetent individual, the removal of the photo-damaged cells from the blood by the reticuloendothelial system and the preferential induction of an immune response against cells of the pathologically expanded clone(s).
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PMID:Photopheresis: a clinically relevant immunobiologic response modifier. 179 5

Over the past decade monoclonal antibodies have been successfully employed in a number of animal models of autoimmune disease. We have used antibodies to the class II gene products of the major histocompatibility complex, the CD4 molecule on helper T cells, and the T-cell receptor. Monoclonal anti-class II antibodies have been administered to treat paralytic disease in the animal model of multiple sclerosis--experimental allergic encephalomyelitis. These antibodies not only reverse acute paralytic disease but also decrease the number of relapses in a model of relapsing/remitting multiple sclerosis when given after the first attack. The advantage of this form of therapy is that it is haplotype specific. In other words, in a heterozygous individual it is possible to block the major histocompatibility gene associated with disease susceptibility while leaving other major histocompatibility gene products free for antigen presentation. Thus, animals given this form of immunotherapy are not significantly immunosuppressed. Antibodies to the CD4 molecule have been equally effective in treating animal models of autoimmunity. We and others have reversed ongoing paralysis in experimental autoimmune encephalomyelitis. Relapses have been diminished after the administration of anti-CD4. Antibodies to CD4 have been used successfully to treat animal models of systemic lupus erythematosus, rheumatoid arthritis and myasthenia gravis. Recent trials with anti-CD4 have been successful in the treatment of rheumatoid arthritis and cutaneous T-cell lymphoma. The latter trial employed a chimeric human/mouse antibody. Antibodies to the variable region of the T-cell receptor have been employed to treat experimental autoimmune encephalomyelitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The use of monoclonal antibodies for treatment of autoimmune disease. 208 87

Sera obtained from patients with systemic lupus erythematosus (SLE) were tested for their reactivity to cell lines derived from cutaneous T-cell lymphoma (CTCL), or adult T cell leukaemia (ATL), and with other cell lines, by indirect immunofluorescence method. Approximately one half of SLE sera reacted with the surface antigens of HUT-102 cells, a cell line from CTCL, which constitutively expresses Tac antigen. The titre tended to be higher in the active than in the inactive stage. These positive sera also reacted with other neoplastic or normal T cell lines having Tac antigen. SLE sera reacting with HUT-102 surface antigens were further examined for their reactivities to Tac antigen, the putative IL-2 receptor, using HUT-102 or ATL-2. Pretreatment with anti-Tac monoclonal antibody partially blocked the reactivities to HUT-102 surface antigens in nine of 15 SLE sera tested. The binding of 125I-labelled anti-Tac monoclonal antibody was displaced by the addition of sera from six of 15 SLE patients. In addition, nine of the 15 SLE sera could inhibit the binding of 125I-labelled IL-2 to ATL-2 cells. These results suggested that some of SLE sera contained antibodies against the IL-2 receptor.
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PMID:Systemic lupus erythematosus sera antilymphocyte reactivity: detection of antibodies to Tac-antigen positive T cell lines. 300 53

Photopheresis is an apheresis-based therapy that is currently available at approximately 70 medical centers worldwide. Recent evidence indicates that extracorporeal photopheresis can significantly prolong life as well as induce a 60-75% response rate among individuals with advanced cutaneous T-cell lymphoma (CTCL). Moreover, a 10-15% cure rate, in response to photopheresis alone, or in combination with interferon-alpha, has been obtained at our institution. These complete responses have been characterized by the complete disappearance of morphologically atypical cells from the skin and blood. Southern blot analysis of peripheral blood specimens has also confirmed the indefinite disappearance of the malignant T-cell clone from the blood of patients with complete responses. Current immunological data obtained from in vitro human studies and from animal models suggest that the basis for the responses of CTCL patients are related to activation of treated macrophages resulting in release of cytokines, including substantial levels of tumor necrosis factor alpha (TNF-alpha), and perhaps, to the induction of anticlonotypic immunity directed against pathogenic clones of T lymphocytes. In addition to the treatment of CTCL, a potential role for photopheresis in the therapy of autoimmune disease has been suggested by recent pilot studies of pemphigus vulgaris, rheumatoid arthritis, and systemic lupus erythematosus. Furthermore, a randomized, single-blinded trial involving 79 patients with early onset, aggressive systemic sclerosis suggested that photopheresis could benefically affect the course of the cutaneous thickening in this form of the disease. Lastly, two independent pilot studies of cardiac transplantation have indicated that photopheresis can reverse acute cardiac allograft rejection and potentially suppress ongoing chronic rejection. Randomized, controlled trials for these new indications for photopheresis therapy are currently in the early stages of implementation.
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PMID:Review of immunomodulation by photopheresis: treatment of cutaneous T-cell lymphoma, autoimmune disease, and allograft rejection. 788 25

Photopheresis is a pheresis-based therapy that is currently available at approximately 70 medical centers worldwide. Recent evidence indicates that extracorporeal photopheresis can significantly prolong life, as well as induce a 60-75% response rate among individuals with advanced cutaneous T-cell lymphoma (CTCL). Moreover, a 10-15% cure rate, in response to photopheresis alone, or in combination with interferon alfa, has been obtained at our institution. These complete responses have been characterized by the complete disappearance of morphologically atypical cells from the skin and blood. Southern blot analysis of peripheral blood specimens have also confirmed the indefinite disappearance of the malignant T-cell clone from the blood of patients with complete responses. Current immunological data obtained from in vitro human studies and from animal models suggest that the basis for the responses of CTCL patients are related to activation of treated macrophages resulting in release of cytokines, including substantial levels of TNF alfa, and, perhaps, to the induction of anti-clonotypic immunity directed against pathogenic clones of T-lymphocytes. In addition to the treatment of CTCL, a potential role for photopheresis in the therapy of autoimmune disease has been suggested by recent pilot studies of pemphigus vulgaris, rheumatoid arthritis, and systemic lupus erythematosus. Furthermore, a randomized, single-blinded trial involving 79 patients with early onset, aggressive systemic sclerosis suggested that photopheresis could beneficially effect the course of the cutaneous thickening in this form of the disease. Lastly, two independent pilot studies of cardiac transplantation have indicated that photopheresis can reverse acute cardiac allograft rejection and potentially suppress ongoing chronic rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of extracorporeal photopheresis in the treatment of cutaneous T-cell lymphoma, autoimmune disease, and allograft rejection. 819 9

The antiphospholipid syndrome is an acquired multisystem disorder of hypercoagulation, which may be primary or secondary to underlying diseases. Serologic markers for the syndrome are the lupus anticoagulant and anticardiolipin antibodies. Clinical features include recurrent thrombotic events (arterial or venous), repeated fetal loss, and thrombocytopenia. Cutaneous manifestations may occur as the first sign of antiphospholipid syndrome. These include livedo reticularis, necrotizing vasculitis, livedoid vasculitis, thrombophlebitis, cutaneous ulceration and necrosis, erythematous macules, purpura, ecchymoses, painful skin nodules, and subungual splinter hemorrhages. Antiphospholipid syndrome may also be associated rarely with anetoderma, discoid lupus erythematosus, cutaneous T-cell lymphoma, or disorders that closely resemble Sneddon or Degos syndromes. Noninflammatory vascular thrombosis is the most frequent histopathologic feature observed. Prophylaxis and treatment of thrombosis in patients with antiphospholipid syndrome relies principally on anticoagulant and antiplatelet agents.
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PMID:Antiphospholipid syndrome and the skin. 920 65

Lupus erythematosus (LE) is a disease with a wide spectrum of cutaneous and systemic manifestations. Discoid LE (DLE) is the most common form of cutaneous LE; the disseminated form of DLE is rare. We report an encouraging response to treatment with extracorporeal photopheresis (ECP) in a single patient with disseminated DLE who did not respond to conventional therapy. To the best of our knowledge this is the first successful use of ECP in the management of such a patient. Extracorporeal photopheresis is a therapeutic modality that has been under investigation for more than 12 years. Although originally developed for the treatment of cutaneous T-cell lymphoma, ECP has recently been used for the management of autoimmune diseases including systemic scleroderma, pemphigus vulgaris and SLE, as well as prevent organ rejection in patients with cardiac or kidney transplants and graft versus host disease after bone marrow transplantation.
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PMID:[Extracorporeal photopheresis in therapy-refractory disseminated discoid lupus erythematosus]. 967 77

DAB(389)IL-2 (denileukin diftitox, ONTAK) is an interleukin-2 receptor (IL-2R)-specific ligand fusion protein that may potentially be selective for IL-2R-expressing malignancies. The activity of DAB(389)IL-2 in the treatment of cutaneous T-cell lymphoma has established the feasibility of utilizing such a targeted therapeutic in disseminated disease with acceptable toxicity. Data from the phase I trial suggest that the definition of activity in other cancer types, including other non-Hodgkin's lymphomas (NHL), is warranted. Three NHL patients in this study responded, two of whom had follicular lymphomas, with the third having a primary intermediate-grade B-cell NHL that was refractory to chemotherapy and stem cell transplant. This patient has remained in complete remission over 3 years after treatment with DAB(389)IL-2. Patients treated to date have had IL-2R-positive tumors, but this remains a very complex clinical issue. The need for a threshold level of receptor expression, the difficulty in obtaining representative tissue, the lack of an assay that accurately reflects high-affinity receptor, and the potential difficulty of observer variability in evaluating the assays should point us toward examining response rates in cancer patients where IL-2R cannot be detected or is unknown. The potential to target the high-affinity IL-2R supports the development of this agent in transplantation and in autoimmune diseases. Targeting IL-2R-expressing lymphocytes may be an effective strategy for the prevention of graft rejection and to treat or prevent graft-versus-host disease. DAB(389)IL-2 has been examined in clinical trials of psoriasis and rheumatoid arthritis and has shown promising results. The potential utility in other autoimmune disorders is unknown, but diseases such as systemic lupus, scleroderma, and vasculitis also may be effective candidates for such ligand fusion therapy.
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PMID:DAB(389)IL-2 (denileukin diftitox, ONTAK): other potential applications. 1170 62

Long-wavelength ultraviolet A (340-400 nm; UVA1) therapy is currently available in only a few dermatology departments. Equipment capable of delivering this waveband has been available since 1981, but it is only over the past decade that increasing numbers of studies assessing the potential of this as a therapy have been published. High-dose UVA1, which requires expensive and space-occupying apparatus, is effective as a monotherapy for acute flares of atopic dermatitis, but it has not yet been formally assessed as an adjunct, rather than as an alternative to conventional therapies including potent and very potent topical corticosteroids. Low-dose (which can be administered using a standard phototherapy cubicle fitted with appropriate lamps) and medium-dose UVA1 may be less effective for this indication. Another condition for which UVA1 is effective, and is particularly promising because we have no reliably effective treatment already, is localized scleroderma. It also appears to be effective in systemic lupus erythematosus (although it is not yet clear when it is indicated, and its safety needs to be assessed in more patients) and in polymorphic light eruption (although there have been no studies suggesting that UVA1 will have any advantages over standard prophylactic phototherapies). Open studies and case series suggest that UVA1 may prove beneficial for various other diseases, including cutaneous T-cell lymphoma, lichen sclerosus, keloids, systemic sclerosis and hand dermatitis. In the centres where it is available, UVA1 has already proved a useful addition to the range of phototherapies previously available. However, much more research is needed to confirm its efficacy for many of its potential indications, and to determine when and how it should be used.
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PMID:Ultraviolet A1 phototherapy. 1275 18

Chronic graft-versus-host disease (GvHD) affects 50% of long-term bone marrow transplant survivors and remains a cause of major long-term morbidity in these patients despite aggressive therapy. Extracorporeal photochemotherapy (ECP), considered as an effective treatment for patients with erythrodermic cutaneous T-cell lymphoma (CTCL), has recently been used successfully in the treatment of GvHD. One of the most intriguing aspects of ECP is its ability to induce two apparently opposite effects: activation of the immune system against neoplastic cells (as in CTCL) and downregulation of the activity of T-cell clones in autoimmune diseases (as in systemic sclerosis, systemic lupus erythematosus and pemphigus vulgaris) and autoallogeneic immune responses (as in GvHD and allograft rejection). Only a better and more complete understanding of the various mechanisms involved will enable this interesting new therapy to be made more effective and selective.
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PMID:Mechanism of action of extracorporeal photochemotherapy in chronic graft-versus-host disease. 1521 89


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