Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Viral and bacterial infections may serve as an environmental trigger for the development or exacerbation of systemic lupus erythematosus (SLE) in the genetically predetermined individual. In addition, SLE patients are more prone to develop common (pneumonia, urinary tract infection, cellulitis, sepsis), chronic (tuberculosis), and opportunistic infections possibly due to inherit genetic and immunologic defects (complement deficiencies, mannose-binding lectin [MBL] polymorphisms, elevated Fcgamma III and GM-CSF levels, osteopontion polymorphism), but also due to the broad spectrum immunosuppressive agents that are part of therapy for severe manifestations of the disease. Hence, SLE patients are considered a high-risk population, where identification and treatment of chronic infections such as tuberculosis, hepatitis B or human immunodeficiency virus, are important prior to the institution of immunosuppression so as to prevent reactivation or exacerbation of the infection. Infections in SLE patients remain a source of morbidity and mortality. A caveat often encountered is to distinguish between a lupus flare and an acute infection; in such cases parameters including elevated CRP (and adhesion molecules) may aid in the diagnosis of infection. Recent research has provided convincing evidence that EBV infection may play a major role not only in molecular mimicry but also in aberrations of B cells and apoptosis leading to a state of perpetual heightened immune response in SLE.
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PMID:Infections and SLE. 1637 52

Skin disfigurations and pruritus can pose severe threats to quality of life, and treatment options for patients with recalcitrant diseases are limited. Tumor necrosis factor alpha, a proinflammatory cytokine, appears to play a central role in mediating the symptoms of many skin disorders. We report cases in which etanercept (Enbrel; Immunex Corp, Thousand Oaks, Calif), a tumor necrosis factor alpha antagonist that is approved for the treatment of moderate to severe psoriasis, was administered to ameliorate the symptoms of acute and chronic dermatologic conditions, including Hailey-Hailey disease, severe psoriasis, dermatomyositis, and subacute cutaneous lupus erythematosus. Treatment with etanercept substantially improved the clinical symptoms and quality of life in these patients, and may offer a therapeutic option for some patients with severe skin disorders.
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PMID:Case reports of etanercept in inflammatory dermatoses. 1648 29

Autoantibody-mediated compromise of central neurotransmission is a pathogenic mechanism proposed in etiology of neuropsychiatric lupus (NP-SLE). Recent experimental data support the hypothesis that intrathecally-synthesized antibodies play a key role in brain damage and behavioral dysfunction. However, autoantibody-producing plasma cells have not yet been detected in brain tissue. We presently use contemporary immunohistochemical markers and flow cytometry to assess distribution and prevalence of plasma cells and other phenotypes, which infiltrate brains of lupus-prone MRL-lpr mice. The functional status of infiltrates was confirmed by in situ hybridization for TNF-alpha mRNA. Consistent with the notion of breached blood-CSF and blood-brain barriers, CD3+ T-cells (approximately 20% of the mononuclear cell infiltrate) were plentiful in choroid plexuses and commonly seen around blood vessels. The CD138+ plasma cells were restricted to the choroid plexus and stria medullaris of diseased MRL-lpr mice. Although accounting for less than 1% of the total cell infiltrate, CD19+IgM+ B-cells increased with age in brains of MRL-lpr mice. Severe mononuclear cell infiltration was accompanied by splenomegaly and retarded brain growth. The results obtained support the hypothesis of progressive neurodegeneration as a consequence of leukocyte infiltration and intrathecal autoantibody synthesis. Further characterization of neuroactive antibodies and their targets may contribute to a better understanding of brain atrophy and behavioral dysfunction in the MRL model, and potentially in NP-SLE.
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PMID:Distribution and prevalence of leukocyte phenotypes in brains of lupus-prone mice. 1690 95

B lymphocyte chemoattractant (BLC/CXCL13) is ectopically and highly expressed in the target organs such as the thymus and kidney in aged (NZB x NZW)F1 (BWF1) mice, a murine model for SLE. Ectopic expression of BLC/CXCL13 was attributed to mature myeloid DCs infiltrating in the target organs. DCs were also increased in the peripheral blood in aged BWF1 mice and differentiated into BLC/CXCL13-producing DCs in the presence of TNF-alpha or IL-1beta, but not IFN-alpha or IFN-gamma. BLC/CXCL13 expression in mature myeloid DCs was confirmed in bone marrow derived-DCs generated in vitro in the presence of GM-CSF and TNF-alpha. B1 cells expressed higher level of CXCR5 and migrated towards BLC/CXCL13 much better than B2 cells. B1 cells failed to home to the peritoneal cavity and preferentially recruited to the target organs in aged BWF1 mice developing lupus nephritis. B1, but not B2 cells possessed a potent antigen presenting activity in allo-MLR and activated autologous thymic CD4 T cells in the presence of IL-2. CXCR5+ CD4 T cells were also increased in aged BWF1 mice and they enhanced IgG production by B1 cells in vitro. These results suggest a possible involvement of aberrant B1 cell trafficking in activation of autoreactive CD4 T cells and autoantibody production in the target organs during the development of lupus, providing a new insight for the pathogenesis of B1 cells in lupus.
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PMID:Aberrant B1 cell trafficking in a murine model for lupus. 1712 21

Patients with systemic lupus erythematosus (SLE) experience a wide array of neurologic (N) and psychiatric (P) events, some of which are directly attributable to lupus. Regardless of attribution, NP events have a significant impact on individual patient's health-related quality of life. Primary immunopathogenic mechanisms of NP-SLE include vasculopathy, autoantibody production, and intrathecal inflammatory mediators. The recently described anti-NR2 glutamate receptor antibodies have been implicated in animal models of neuronal injury, but their role in the pathogenesis of human NP-SLE is unclear. The diagnosis of NP-SLE remains largely one of exclusion, although the detection of select autoantibodies, CSF analysis, and appropriate use of neuroimaging and neuropsychometric testing may provide support in the evaluation of individual patients. Therapeutic options include symptomatic therapies, immunosuppression, and anticoagulation.
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PMID:New insights into central nervous system lupus: a clinical perspective. 1750 41

Catastrophic longitudinal myelitis is an extremely rare neurologic manifestation of collagen vascular disease, described heretofore in 11 cases of SLE and 1 of Sjogren's Syndrome. This report documents markedly abnormal and worsening CSF findings on sequential CSF examinations over a period of three days (WBC >1500 cells/microL, >80% neutrophils, markedly elevated protein, and extremely low glucose levels) in the absence of infection. These abnormalities cleared rapidly with institution of immunosuppressive therapy so that a third CSF exam done within three days revealed almost complete normalization of CSF values. These findings suggest that in some cases of CLM a strong inflammatory component may be present, while in others, other pathogenic factors may predominate.
Lupus 2007
PMID:Marked inflammation in catastrophic longitudinal myelitis associated with systemic lupus erythematosus. 1789 6

Previous studies have shown that treatment of ovariectomized females with 17-beta estradiol (E2) accelerates the development of autoimmunity in the (NZBxNZW)F(1) murine lupus model. Treatment with estrogenic organochlorine pesticides (OCPs) such as chlordecone produces a similar effect. Although it is reasonable to postulate that the effects of chlordecone and related OCPs on autoimmunity are due to their estrogenic effects, this has not been clearly demonstrated. The objective of this study was to compare effects of chlordecone and E2 on splenic T lymphocyte parameters plausibly related to autoimmunity; specifically, on T-cell phenotype and functions. Ovariectomized (NZBxNZW)F(1) mice were treated for 6 weeks with implanted sustained-release pellets containing chlordecone or E2 at dosing rates shown previously to significantly shorten time to onset of disease. E2, but not chlordecone, increased the percentage of activated and memory CD4 T-cells, and reduced naive CD4 T-cells. E2 also elevated CD25 and glucocorticoid-induced TNF receptor (GITR) levels in CD4 T-cells, an effect not shared by chlordecone. On the other hand, both chlordecone and E2 increased Bcl-2 expression in CD4 T-cells and reduced CD4 T-cell apoptosis without affecting their proliferation. Although both treatments increased TNF-alpha and IL-2 secretion by CD4 T-cells, only chlordecone increased secretion of IFN-gamma and GM-CSF. E2, but not chlordecone, increased IL-10 secretion. These observations indicate that although it is considered an estrogenic OCP, chlordecone exerts effects on splenic T-cells that are different in a number of ways from E2.
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PMID:Comparison of chlordecone and estradiol effects on splenic T-cells in (NZBxNZW)F(1) mice. 1895 62

Idiosyncratic drug reactions represent a serious health problem, and they remain unpredictable largely due to our limited understanding of the mechanisms involved. Penicillamine-induced autoimmunity in Brown Norway (BN) rats represents one model of an idiosyncratic reaction, and this drug can also cause autoimmune reactions in humans. We previously demonstrated that penicillamine binds to aldehydes on the surface of macrophages. There is evidence that an imine bond formed by aldehyde groups on macrophages and amine groups on T cells is one type of interaction between these two cells that is involved in the induction of an immune response. We proposed that the binding of penicillamine with aldehyde groups on macrophages could lead to their activation and in some patients could lead to autoimmunity. In this study, the transcriptome profile of spleen macrophages 6 h after penicillamine treatment was used to detect effects of penicillamine on macrophages with a focus on 20 genes known to be macrophage activation biomarkers. One biological consequence of macrophage activation was investigated by determining mRNA levels for IL-15 and IL-1 beta which are crucial for NK cell activation, as well as levels of mRNA for selected cytokines in spleen NK cells. Up-regulation of the macrophage activating cytokines, IFN-gamma and GM-CSF, and down-regulation of IL-13 indicated activation of NK cells, which suggests a positive feedback loop between macrophages and NK cells. Furthermore, treatment of a murine macrophage cell line, RAW264.7, with penicillamine increased the production of TNF-alpha, IL-6, and IL-23, providing additional evidence that penicillamine activates macrophages. Hydralazine and isoniazid cause a lupus-like syndrome in humans and also bind to aldehyde groups. These drugs were also found to activate RAW264.7 macrophages. Together, these data support the hypothesis that drugs that bind irreversibly with aldehydes lead to macrophage activation, which in some patients can lead to an autoimmune syndrome.
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PMID:D-penicillamine-induced autoimmunity: relationship to macrophage activation. 1957 32

Neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE) is a life-threatening disorder and early diagnosis and proper treatment are critical in the management of this neuropsychiatric manifestations in lupus. Brain magnetic resonance imaging (MRI), electroencephalogram (EEG), neuropsychological tests, and lumbar puncture are clinical used for the diagnosis of NPSLE. In addition to these tests, cytokine and chemokine levels in CSF have been reported as useful diagnostic marker of NPSLE. Based on the number of recently published studies, this review overviewed the roles of cytokines and chemokines in NPSLE.
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PMID:Cytokines and chemokines in neuropsychiatric syndromes of systemic lupus erythematosus. 2061 45

Current views suggest that prothrombotic properties of antiphospholipid antibodies (aPL) have a role in the development of acute transverse myelitis (ATM) in patients with systemic lupus erythematosus (SLE). Consequently, empiric anticoagulation may be included in these patients' treatment. We performed a systemic review of the literature to explore the clinical value of the presence of aPL in patients with lupus myelitis and the possible effectiveness of anticoagulation. We analyzed clinical and laboratory data extracted from published cases of SLE-associated ATM, fulfilling the Transverse Myelitis Consortium Working Group diagnostic criteria, that provided information on aPL. We report on a total of 70 patients. aPL, detected upon ATM onset in 54% of patients, neither predicted the involvement of the thoracic part of the spine, which has been postulated to reflect a predominantly thrombosis-induced injury, nor correlated with relapsing ATM, additional lupus CNS manifestations, or worse clinical outcome. An unfavorable outcome could be predicted by paralysis (P=0.02) and abnormal CSF findings at presentation (P=0.02). Whilst all patients received major immunosuppressive regimens, severe neurologic impairment (estimated Expanded Disability Status Scale score>7) was found primarily in aPL-negative patients (P=0.03). Anticoagulation was more frequently applied in aPL-positive patients (P=0.04), but any additional therapeutic effect was not evident. Detection of circulating aPL at ATM onset appears unreliable to suggest a thrombotic cause and perhaps not enough to dictate therapeutic anticoagulation. Registry creation of ATM in patients with SLE is needed to obtain more definite answers on the role of aPL in this condition.
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PMID:Acute transverse myelitis and antiphospholipid antibodies in lupus. No evidence for anticoagulation. 2084 Mar 79


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