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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myasthenia gravis (MG) represents the prototypic autoimmune disorder with well characterized immunopathology. Advances in the diagnosis and treatment of this neuromuscular transmission disorder have significantly improved the management of myasthenic patients. Unfortunately the currently available immunomodulating treatments have significant side effects and some patients do not tolerate them or adequately respond to them. Therefore the possibility of a new immunosuppressant agent that is safe, effective and has steroid-sparing effect is very appealing. Mycophenolate mofetil (MMF) has shown promising effects in MG patients in preliminary studies and is currently being studied in two prospective, randomized, double-blind, placebo controlled, multicenter trials to better establish its role in the treatment of MG.
Lupus 2005
PMID:Mycophenolate mofetil and myasthenia gravis. 1580 32

Systemic lupus erythematosus is a multigenic disorder of unknown etiology. To investigate the role of specific genes in lupus, we have examined the effects of single gene deletions on mercury-induced autoimmunity. Deficiency of certain genes abrogated induction of autoimmunity, while absence of others had little effect. The most interesting observations were obtained with genes related to interferon-gamma. Genes involved in upregulation of IFN-gamma expression did not significantly influence autoimmunity whereas absence of IFN-gamma or IFN-gamma receptor led to greatly reduced autoantibody responses and immunopathology. Absence of IRF-1, a gene expressed in response to IFN-gamma, resulted in selective retention of anti-chromatin autoantibodies demonstrating that specific defects in signaling pathways and gene expression subsequent to IFN-gamma/IFN-gamma receptor interaction influence specific disease parameters. These studies show that single gene deletions can have various outcomes ranging from no effect, suppression of one or more features of disease, to suppression of all features of disease, and that all three outcomes can be observed in the IFN-gamma pathway. IFN-gamma influences the expression and function of other lupus relevant genes such as IL-6 and beta2microglobulin, therefore the effects of these gene deletions on disease expression may also reflect responses downstream of IFN-gamma function.
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PMID:Immunology and genetics of induced systemic autoimmunity. 1599 75

Following tetanus vaccination, a wave of antibody-secreting cells appear in the peripheral blood composed of vaccine-specific, migratory plasmablasts and plasma cells secreting antibodies specific for other antigens. The latter probably were tissue resident plasma cells formed in earlier immune responses that are mobilized due to competition with the newly formed tetanus-specific plasmablasts. Newly formed plasma cells secreting antibodies specific for a particular antigen/vaccine are accommodated in the bone marrow likely at the global expense of the pre-existing long-lived plasma cell population providing humoral memory for other antigens. Plasmablasts but not mature plasma cells are attracted by the ligands for the chemokine receptors CXCR4 and CXCR3. While CXCR4 and its cognate ligand is important for plasma cell homing to the bone marrow, CXCR3 and its ligand IP10 are likely to be involved in attracting them to inflamed tissue. In NZB/W mice, a model for systemic lupus, long-lived autoreactive plasma cells are present not only in bone marrow, but also in inflamed tissues and spleen. Autoreactive plasma cells in the spleen are present long before the onset of the disease, suggesting that these cells contribute to induction of immunopathology.
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PMID:Long-lived plasma cells in immunity and immunopathology. 1628 Jan 69

Interleukin-10 (IL-10) is a potent anti-inflammatory and immunosuppressive cytokine secreted by several cell types. Most anti-inflammatory effects of IL-10 are caused by its ability to deactivate macrophages and monocytes, whereas its immunosuppressive properties are due to functional inhibition of both antigen-presenting cells and T cells. On the other hand, IL-10 also exerts immunostimulatory effects, especially on B cells, CD8+ cytotoxic T cells and natural killer cells. In vivo administration of recombinant IL-10 (rIL-10) efficiently prevents experimental septic shock induced by endotoxin, staphylococcal superantigen or cecal ligation and puncture, as well as experimental autoimmune diseases mediated by T helper type 1 (T(H)1) cells and other inflammatory disorders. rIL-10 exerts paradoxical effects in cancer models, where it promotes tumour rejection, probably due to its stimulatory properties on cytotoxic cells. On the other hand, rIL-10 increases the severity of experimental infections caused by fungi or bacteria, and enhances systemic autoimmune features in mice with spontaneous lupus syndrome. Although the therapeutic potential of rIL-10 in human diseases seems promising, the multiple facets of rIL-10 in experimental immunopathology indicate that the success of clinical trials with rIL-10 will depend both on the appropriate selection of the patient populations to be treated and on the early detection of possible adverse effects.
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PMID:Interleukin-10: actions and therapeutic potential. 1803 Oct 75

Ample evidence suggests a role of TGF-beta in preventing autoimmunity. Multiorgan inflammatory disease, spontaneous activation of self-reactive T cells, and autoantibody production are hallmarks of autoimmune diseases, such as lupus. These features are reminiscent of the immunopathology manifest in TGF-beta1-deficient mice. In this study, we show that lupus-prone (New Zealand Black and White)F(1) mice have reduced expression of TGF-beta1 in lymphoid tissues, and TGF-beta1 or TGF-beta1-producing T cells suppress autoantibody production. In contrast, the expression of TGF-beta1 protein and mRNA and TGF-beta signaling proteins (TGF-beta receptor type II and phosphorylated SMAD3) increases in the target organs, i.e., kidneys, of these mice as they age and develop progressive organ damage. In fact, the levels of TGF-beta1 in kidney tissue and urine correlate with the extent of chronic lesions that represent local tissue fibrosis. In vivo TGF-beta blockade by treatment of these mice with an anti-TGF-beta Ab selectively inhibits chronic fibrotic lesions without affecting autoantibody production and the inflammatory component of tissue injury. Thus, TGF-beta plays a dual, seemingly paradoxical, role in the development of organ damage in multiorgan autoimmune diseases. According to our working model, reduced TGF-beta in immune cells predisposes to immune dysregulation and autoantibody production, which causes tissue inflammation that triggers the production of anti-inflammatory cytokines such as TGF-beta in target organs to counter inflammation. Enhanced TGF-beta in target organs, in turn, can lead to dysregulated tissue repair, progressive fibrogenesis, and eventual end-organ damage.
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PMID:Dual roles of immunoregulatory cytokine TGF-beta in the pathogenesis of autoimmunity-mediated organ damage. 1820 88

An increasing body of evidence suggests that CD1d-restricted invariant natural killer T (iNKT) cells play an important immunoregulatory role in a variety of autoimmune diseases in both humans and mouse models. Their role in systemic lupus erythematosus (SLE), however, is not fully determined, as SLE mouse models have yielded conflicting results demonstrating both a protective function and a pathogenic role. The reduced frequency of iNKT cells in peripheral blood of lupus patients supports the idea of a protective role for these cells in the immunopathology of SLE. Therapeutic approaches using glycolipids provide a promising tool to correct numerical iNKT cell deficiencies and to modulate their function. This review highlights the potential role of iNKT cells in lupus immunopathology and summarizes recent studies concerning iNKT cells in SLE patients, lupus-prone murine models and glycolipid therapy.
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PMID:The role of iNKT cells in the immunopathology of systemic lupus erythematosus. 1975 83

Cutaneous lupus erythematosus (LE) may present in a variety of clinical forms. Three recognized subtypes of cutaneous LE are acute cutaneous LE (ACLE), subacute cutaneous LE (SCLE), and chronic cutaneous LE (CCLE). ACLE may be localized (most often as a malar or 'butterfly' rash) or generalized. Multisystem involvement as a component of systemic LE (SLE) is common, with prominent musculoskeletal symptoms. SCLE is highly photosensitive, with predominant distribution on the upper back, shoulders, neck, and anterior chest. SCLE is frequently associated with positive anti-Ro antibodies and may be induced by a variety of medications. Classic discoid LE is the most common form of CCLE, with indurated scaly plaques on the scalp, face, and ears, with characteristic scarring and pigmentary change. Less common forms of CCLE include hyperkeratotic LE, lupus tumidus, lupus profundus, and chilblain lupus. Common cutaneous disease associated with, but not specific for, LE includes vasculitis, livedo reticularis, alopecia, digital manifestations such as periungual telangiectasia and Raynaud phenomenon, photosensitivity, and bullous lesions. The clinical presentation of each of these forms, their diagnosis, and the inter-relationships between cutaneous LE and SLE are discussed. Common systemic findings in SLE are reviewed, as are diagnostic strategies, including histopathology, immunopathology, serology, and other laboratory findings. Treatments for cutaneous LE initially include preventive (e.g. photoprotective) strategies and topical therapies (corticosteroids and topical calcineurin inhibitors). For skin disease not controlled with these interventions, oral antimalarial agents (most commonly hydroxychloroquine) are often beneficial. Additional systemic therapies may be subdivided into conventional treatments (including corticosteroids, methotrexate, thalidomide, retinoids, dapsone, and azathioprine) and newer immunomodulatory therapies (including efalizumab, anti-tumor necrosis factor agents, intravenous immunoglobulin, and rituximab). We review evidence for the use of these medications in the treatment of cutaneous LE.
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PMID:Cutaneous lupus erythematosus: issues in diagnosis and treatment. 1982 38

Systemic lupus erythematosus (SLE or lupus) is a polygenic syndrome of immunity against nuclear autoantigens. Recent data from several fields now suggest 'pseudoviral' immunity as a novel disease concept. Known lupus risk factors commonly compromise those mechanisms that protect chromatin and ribonucleoprotein particles from activating viral nucleic acid sensors. This process activates antigen-presenting cells and induces type I interferons. These central mediators of antiviral immunity have similar proinflammatory roles in lupus, explaining overlapping clinical manifestations, immunopathology and ultrastructural abnormalities in systemic viral infection and lupus. Structurally, chromatin and ribonucleoprotein particles resemble viral particles and have a similar potency to trigger antigen-specific B- and T-cell responses. Therefore, self nucleic acid-driven 'pseudoviral' immunity is evolving as another concept in understanding the pathogenesis of lupus and may offer novel targets for therapy.
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PMID:Pseudoviral immunity - a novel concept for lupus. 1989 18

The prototypic autoimmune disease, SLE, is known to be associated with polyclonal B cell hyperreactivity. Developing an understanding of the complex nature of human B cell differentiation, largely through the application of multiparameter flow cytometry to an analysis of circulating B cells has permitted an assessment of whether specific stages of B cell maturation are affected by the tendency for polyclonal B cell activation. Moreover, the analysis of perturbations of the specific stages of B cell maturation has generated new information on whether abnormalities in B cell differentiation are primarily involved in autoimmune disease immunopathology or, rather, are secondary to the inflammatory environment characteristic of subjects with this autoimmune disease. Multivariant analysis has begun to document abnormalities in B cell maturation that are primarily associated with lupus, or, alternatively related to disease duration, disease activity and concomitant medication. Together, these analyses have provided new insights on the role of B cell over-reactivity in SLE.
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PMID:Abnormalities of B cell subsets in patients with systemic lupus erythematosus. 2059 9

Heterologous immunity is a common phenomenon present in all infections. Most of the time it is beneficial, mediating protective immunity, but in some individuals that have the wrong crossreactive response it leads to a cascade of events that result in severe immunopathology. Infections have been associated with autoimmune diseases such as diabetes, multiple sclerosis and lupus erythematosis, but also with unusual autoimmune like pathologies where the immune system appears dysregulated, such as, sarcoidosis, colitis, panniculitis, bronchiolitis obliterans, infectious mononucleosis and even chronic fatigue syndrome. Here we review the evidence that to better understand these autoreactive pathologies it requires an evaluation of how T cells are regulated and evolve during sequential infections with different pathogens under the influence of heterologous immunity.
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PMID:Heterologous immunity: immunopathology, autoimmunity and protection during viral infections. 2125 Aug 37


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