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)

A strong association has been found between complement and common connective tissue diseases, such as systemic lupus erythema and Henoch Schoenlein Purpura. This has led to the notion that the pathogenesis of such diseases may involve a defect in the safe disposal of immune complexes, which is mediated by complement. To bring further light on this subject, a sensitive assay was developed to measure the ability of serum to prevent immune precipitation. This assay was then employed to study various Icelandic patient groups, and a defect in this function of complement was found to be common in patients with systemic lupus erythematosus and systemic sclerosis. Partial deficiency in complement C4A (C4A Q0) can not account for this defect, as it was not observed in patients with diabetes, gluten-sensitive enteropathy or autoimmune thyroiditis, in which C4A Q0 is common. The defect is strongly correlated with anti-C1q antibodies. Further studies are needed to test the possible role of anti-C1q antibodies in the pathogenesis of immune complex disease.
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PMID:[The association of complement with common connective tissue diseases - a review]. 1846 Jul 33

C-reactive protein (CRP) is an acute-phase protein with therapeutic activity in mouse models of systemic lupus erythematosus and other inflammatory and autoimmune diseases. To determine the mechanism by which CRP suppresses immune complex disease, an adoptive transfer system was developed in a model of immune thrombocytopenic purpura (ITP). Injection of 200 microg of CRP 24 h before induction of ITP markedly decreased thrombocytopenia induced by anti-CD41. CRP-treated splenocytes also provided protection from ITP in adoptive transfer. Splenocytes from C57BL/6 mice were treated with 200 microg/ml CRP for 30 min, washed, and injected into mice 24 h before induction of ITP. Injection of 10(6) CRP-treated splenocytes protected mice from thrombocytopenia, as did i.v. Ig-treated but not BSA-treated splenocytes. The suppressive cell induced by CRP was found to be a macrophage by depletion, enrichment, and the use of purified bone marrow-derived macrophages. The induction of protection by CRP-treated cells was dependent on FcRgamma-chain and Syk activation, indicating an activating effect of CRP on the donor cell. Suppression of ITP by CRP-treated splenocytes required Fc gamma RI on the donor cell and Fc gamma RIIb in the recipient mice. These findings suggest that CRP generates suppressive macrophages through Fc gamma RI, which then act through an Fc gamma RIIb-dependent pathway in the recipient to decrease platelet clearance. These results provide insight into the mechanism of CRP regulatory activity in autoimmunity and suggest a potential new therapeutic approach to ITP.
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PMID:Macrophages activated by C-reactive protein through Fc gamma RI transfer suppression of immune thrombocytopenia. 1915 86

Primary immunodeficiency diseases (PID) are a genetically heterogenous group of >150 disorders that affect distinct components of the innate and adaptive immune system and are often associated with autoimmune diseases. We describe PID affecting T-regulatory cells, complement and B cells or their products and discuss the possibility of a cause-effect relationship. The high concordance of T-regulatory cell defects to organ-specific autoimmune disease implies an obligatory role of these cells in maintaining tolerance to epithelial and endocrine tissues; the absence of central nervous system involvement may reflect immunological privilege. Congenital defects in C1q, C1r/s and C4 are strongly associated with systemic lupus erythematosus (SLE), and this pattern along with laboratory evidence suggests a major importance of classical pathway activity in safe elimination of immune complexes and prevention of immune complex disease (ICD). It is debatable whether this ICD is to be regarded as an autoimmune disease (resulting from a breakdown of immunological ignorance to antigens that are normally hidden), as autoantibodies may be absent, and tissue damage because of deposition of immune complexes could account for all of the pathology observed. Evidence for a causative link between primary antibody deficiencies and autoimmune disease is much less compelling and may in fact involve a common genetic background. However, arguments have also been made in favour of the notion that an intense antigen load as a result of recurrent or persistent infections may affect either tolerance or ignorance, e.g. by molecular mimicry or the presence of superantigens. Similar immunological mechanisms might account for the vast majority of autoimmune diseases.
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PMID:Primary immunodeficiency and autoimmunity: lessons from human diseases. 2050 Jun 82

The IFN-regulatory factors IRF1, IRF3, IRF5, and IRF7 modulate processes involved in the pathogenesis of systemic lupus and lupus nephritis, but the contribution of IRF4, which has multiple roles in innate and adaptive immunity, is unknown. To determine a putative pathogenic role of IRF4 in lupus, we crossed Irf4-deficient mice with autoimmune C57BL/6-(Fas)lpr mice. IRF4 deficiency associated with increased activation of antigen-presenting cells in C57BL/6-(Fas)lpr mice, resulting in a massive increase in plasma levels of TNF and IL-12p40, suggesting that IRF4 suppresses cytokine release in these mice. Nevertheless, IRF4 deficiency completely protected these mice from glomerulonephritis and lung disease. The mice were hypogammaglobulinemic and lacked antinuclear and anti-dsDNA autoantibodies, revealing the requirement of IRF4 for the maturation of plasma cells. As a consequence, Irf4-deficient C57BL/6-(Fas)lpr mice neither developed immune complex disease nor glomerular activation of complement. In addition, lack of IRF4 impaired the maturation of Th17 effector T cells and reduced plasma levels of IL-17 and IL-21, which are cytokines known to contribute to autoimmune tissue injury. In summary, IRF4 deficiency enhances systemic inflammation and the activation of antigen-presenting cells but also prevents the maturation of plasma cells and effector T cells. Because these adaptive immune effectors are essential for the evolution of lupus nephritis, we conclude that IRF4 promotes the development of lupus nephritis despite suppressing antigen-presenting cells.
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PMID:IRF4 deficiency abrogates lupus nephritis despite enhancing systemic cytokine production. 2174 31

Systemic lupus erythematosus (SLE) is a polyclonal autoimmune syndrome directed against multiple nuclear autoantigens. Although RNA and DNA seem to have identical immunostimulatory effects on systemic and intrarenal inflammation, each seems to differ with regard to the propensity to induce mitogenic effects such as lymphoproliferation. To identify potential mechanisms by which DNA specifically contributes to the pathogenesis of lupus nephritis, we stimulated cells with immunostimulatory DNA or RNA in vitro and used microarray to compare the transcriptomes of RNA- and DNA-induced genes. Immunostimulatory DNA, but not RNA, induced Mdm2, which is a negative regulator of p53. In vivo, we observed greater expression and activation of Mdm2 in the spleen and kidneys in a mouse model of lupus (MRL-Fas(lpr) mice) than healthy controls. Treatment of MRL-Fas(lpr) mice with the Mdm2 inhibitor nutlin-3a prevented nephritis and lung disease and significantly prolonged survival. Inhibition of Mdm2 reduced systemic inflammation and abrogated immune complex disease by suppressing plasma cells and the production of lupus autoantibodies. In addition, nutlin-3a suppressed the abnormal expansion of all T cell subsets, including CD3(+)CD4(-)CD8(-) T cells, which associated with attenuated systemic inflammation. However, inhibiting Mdm2 did not cause myelosuppression or affect splenic regulatory T cells, neutrophils, dendritic cells, or monocytes. Taken together, these data suggest that the induction of Mdm2 promotes the expansion of plasma cells and CD3(+)CD4(-)CD8(-) T cells, which cause autoantibody production and immune complex disease in MRL-Fas(lpr) mice. Antagonizing Mdm2 may have therapeutic potential in lupus nephritis.
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PMID:Mdm2 promotes systemic lupus erythematosus and lupus nephritis. 2194 95

Immune complex-mediated glomerulonephritis can be caused by a multitude of disease processes and may manifest in a variety of histologic patterns. Lupus nephritis is an immune complex disease, the diagnosis of which requires that the affected patient have systemic lupus erythematosus (SLE). In the absence of SLE, the finding of glomerulonephritis with certain patterns of immune complex deposition characteristic of lupus nephritis has been referred to as lupus-like glomerulonephritis. Immunoglobulin G (IgG), IgA, IgM, complement C3, and C1q deposition in glomerular immune deposits is one such pattern. We report a case of immune complex disease in a primarily membranous distribution with mesangial, subendothelial, and tubular basement membrane deposits with IgG, IgA, IgM, C3, and C1q deposition in a patient with proteinuria, photosensitive dermatitis, and a positive lupus anticoagulant test. The patient had 3 of the clinical criteria for SLE, thus failing to meet the diagnosis based on the American College of Rheumatology definition. In this case, a diagnosis of lupus-like glomerulonephritis was made after other causes of membranous glomerulopathy were excluded. This teaching case highlights the broad differential diagnosis of this pattern of injury and reviews similar cases in the literature.
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PMID:Immune complex disease with a lupus-like pattern of deposition in an antinuclear antibody-negative patient. 2354 58

Human immunodeficiency virus (HIV)-associated lupus-like glomerulonephritis (GN) is a chronic immune complex disease occurring in HIV-infected patients. Although the light, immunofluorescence, and electron microscopy findings indicate features of lupus nephritis, no evidence of systemic lupus erythematosus (SLE) is observed in the affected patients. We present the case of a 45-year-old Caucasian woman with HIV infection who was admitted to the hospital with a nephrotic syndrome 10 years after the HIV diagnosis. A renal biopsy revealed HIV-associated lupus-like GN and necrotizing arteritis affecting two interlobular arteries. Necrotizing arteritis is a type of renal vasculopathy associated with SLE, but has not been reported previously in HIV-associated lupus-like GN. In this case, necrotizing arteritis was found to be a histological feature common to both HIV-associated lupus-like GN and SLE. This histological finding reinforces the resemblance between HIV-associated lupus-like GN and nephritis caused by lupus.
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PMID:Necrotizing arteritis in a human immunodeficiency virus-infected patient with lupus-like glomerulonephritis. 2442 74

Job's syndrome or autosomal dominant hyperimmunoglobulin E syndrome (Hyper-IgE) is a rare disorder that results from a STAT3 gene mutation, which results in the absence of T-helper 17 (Th17) cells and manifests as a severe immunodeficiency. Affected individuals suffer recurrent soft tissue and pulmonary infections among other manifestations, and the spectrum of the disease is still being characterized. We describe 2 sisters with Job's syndrome each with variable expressivity. However, both patients developed proteinuric kidney disease and had biopsies confirming the presence of immune complex glomerulonephritis with staining for immunoglobulins and complement components. Previous reports link Job's syndrome and the development of systemic lupus erythematosus (SLE), but proliferative immune complex glomerulonephritis has not been described. We speculate that continual internal and external antigen exposure may induce an autoimmune process similar to SLE, which in turn may account for the immune complex disease in the kidney.
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PMID:Fraternal twins with job's syndrome and immune complex nephritis. 2850 65

A series of 78 cases of glomerulonephritis (GN), in which renal biopsy revealed changes of GN associated with crescent formation, were reviewed. Renal pathology findings were correlated with clinical features including patient's age, renal function, and serologic findings. In most of the cases (71.8%), the crescents were due to immune complex-mediated GN. This was followed by pauci-immune GN (20.5%) and anti-glomerular basement membrane antibody (GBM) GN (7.7%). The percentage of glomeruli with crescents was the highest in cases of anti-GBM disease (mean of 93.3%), followed by pauci-immune GBM (mean of 48.2%) and immune complex GN (30.9%). In cases with the pauci- immune GN, there were additional features of glomerular injury including fibrinoid necrosis, disruption of the GBM, and rupture of Bowman's capsule. These changes were generally more pronounced in a subset of pauci-immune GN associated with serum elevation of antineutrophil cytoplasmic antibody (c-ANCA). In biopsies from patient with immune complex disease, systemic lupus erythematosus was the most common cause of crescentic GN.
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PMID:Patterns of glomerulonephritis with crescents: Experience at a tertiary medical center in Saudi Arabia. 2854 Aug 89

Lupus nephritis, a well-known complication in systemic lupus erythematosus, is characterised by a proliferative glomerulonephritis or membranous nephropathy along with a full-house immunofluorescence pattern on renal biopsy. There are very few exceptions in which similar histopathological findings are present, but case reports show that an increasing number of HIV-positive patients (mostly black Africans, but also white patients) have HIV-immune complex disease (HIVICK), which can mimic lupus nephritis. Lupus-like HIVICK is treated differently than 'true' lupus nephritis, so distinction is warranted.
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PMID:Nephrotic syndrome due to lupus-like glomerulonephritis in an HIV-positive patient. 2921 16


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