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 structural analysis of cells that contained the interferon-alpha-induced lupus inclusions (LI) was performed using a high-voltage electron microscope to determine the exact cellular location of LI and their association with normal cell organelles. LI were induced in the human B lymphoblastoid cell line, Daudi, by culturing with the pure recombinant human leukocyte interferon, IFLrA. Just prior to harvesting, a portion of the cells was treated with monensin to selectively swell the Golgi apparatus, and thereby simplify their identification using the electron microscope. Organellar associations between LI and the outer nuclear envelope and Golgi apparatus were identified in stereopairs of 1-micron sections prepared from both cells that were not treated with monensin and those that were treated with monensin. Serial 0.25-micron sections of the monensin-treated cells were prepared, and seven arbitrarily chosen cells were examined. Each of these cells contained a single LI, and it formed throughout an endoplasmic-reticulum region that made contact with both the outer nuclear envelope and the Golgi vesicles. Reconstruction of a cell by computer from the digitized negatives of serial sections clearly illustrated these relationships. This study reports the first determination of the association between LI and the Golgi apparatus. It also identifies the presence of only one LI in every cell, and the routine association of the LI with both the outer nuclear envelope and the Golgi apparatus. The unique cell location of LI formation suggests their functioning in membrane biogenesis, the trafficking of proteins to the plasma membrane or to cytoplasmic vesicles, or the processing of proteins for secretion.
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PMID:Localization of interferon-induced lupus inclusions demonstrated by computer image reconstruction of monensin-treated Daudi cells. 137 90

Whether inflammatory bowel diseases (IBD) can be classified as autoimmune disorders is not established. Since circulating acid-labile interferon-alpha (IFN-alpha) is believed to reflect autoimmune reactions, we tested sera from two groups of IBD patients for the presence of circulating IFN. No detectable IFN was found in 51 serum samples of IBD patients. Furthermore, in no serum sample of IBD patients were neutralizing anti-IFN antibodies found. In contrast, acid-labile IFN-alpha was present in sera from 21/52 HIV-infected and from 6/14 systemic lupus erythematosus patients. These observations provide evidence that IBD differs from systemic autoimmune disorders, at least for the presence of circulating IFN.
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PMID:Absence of circulating interferon in patients with inflammatory bowel disease. Suggestion against an autoimmune etiology. 138 5

On the basis of the research on the relationship between human cytomegalovirus (HCMV) infection and systemic lupus erythematosus (SLE) a study of the effects of HCMV infection on the immunological pathogenesis of SLE was undertaken. Presented in this paper is a brief account of the study. It was found that SLE patients with active HCMV infection had significant higher level of serum interferon-alpha (IFN-alpha) than those without active HCMV infection, but the IFN-alpha induction capacity of peripheral blood mononuclear cells (PBMC) from SLE patients with active HCMV infection was evidently poorer than that from patients without it. There was not any statistically significant difference between the two SLE groups in the IFN-gamma induction capacity of PBMC.
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PMID:Immunomodulation of human cytomegalovirus infection on interferon system in patients with systemic lupus erythematosus. 166 8

Several previous reports suggest an association between treatment of patients with interferon-alpha (IFN-alpha) and development of autoantibodies and autoimmune disease. We here summarize the experience from a group of 135 patients with midgut carcinoid tumors treated with natural leukocyte IFN-alpha or recombinant IFN-alpha (rIFN-alpha). An unusual high incidence of antimicrosomal antibodies (MsAb) or anti-thyroglobulin antibodies (TgAb) and thyroid disease manifested as hyperthyroidism, hypothyroidism or a biphasic Hashimoto-like disease was seen, with female predominance. The incidence of antinuclear antibodies (ANA) was also increased, but equally in both sexes. Antibodies to parietal cells were found in 5 cases and 4 patients with pernicious anemia were detected. Two patients developed vasculitis of leukocytoclastic type and one a syndrome resembling systemic lupus erythematosus. Some patients treated with rIFN-alpha develop anti-IFN antibodies. Such antibodies may also be autoantibodies reacting with autologous IFN-alpha. They can neutralize the biologic activity of administrated IFN preparation and cause therapeutic failure. The implications of the various autoimmune manifestations during IFN-alpha treatment are discussed.
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PMID:Autoimmune phenomena in patients with malignant carcinoid tumors during interferon-alpha treatment. 185 11

A 19-year-old man with Philadelphia-positive chronic myelogenous leukemia treated with interferon-alpha (IFN-alpha) therapy for 45 months had systemic lupus erythematosus disease features: malar rash, migratory arthralgias, elevated antinuclear antibodies, elevated antinative DNA, hypocomplementemia, lymphopenia, and proteinuria. After discontinuation of the IFN and initiation of corticosteroids, there was gradual recovery of symptoms, a decline in antinative DNA and antinuclear antibodies to normal levels, and a decrease in proteinuria. The potential association between IFN therapy and the development of systemic lupus erythematosus, and the role of IFN in other autoimmune diseases, is discussed.
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PMID:Development of systemic lupus erythematosus after interferon therapy for chronic myelogenous leukemia. 189 53

Systemic lupus erythematosus (SLE) is characterized by a variety of profound T-cell abnormalities among which are decreased cytotoxic capacity measured by allogeneic cell-mediated lympholysis (CML), natural killer cell (NK) activity, and decreased lymphokine production. In a group of 13 patients with active SLE, allogeneic CML, tested by a 4-hr 51Cr-release assay, was 18.2 +/- 2.7% while in the group of normal individuals CML was 41.2 +/- 2.7%. If optimal doses of affinity-purified interleukin-2 (IL-2) were present during the mixed lymphocyte culture, the CML of SLE patients was increased to normal levels (40.4 +/- 4.0%). In contrast, interferon-alpha (IFN-alpha) increased (but not significantly) the levels of CML. Mixed lymphocyte reaction, tested by tritiated thymidine incorporation, was also decreased in the group of patients (14,820 +/- 815 cpm vs 28,972 +/- 5880 cpm in normals) and it was increased to normal levels if IL-2, but not IFN-alpha was added to the cultures. NK activity was decreased in the group of patients tested by 51Cr-release assay, harvested at 6 and 18 hr. IL-2 increased the NK activity up to normal levels, while IFN-alpha was only partially efficacious. These results demonstrate that IL-2, but not IFN-alpha, can potentiate or even fully restore the deficient cytotoxic effector function of peripheral mononuclear cells in patients with SLE.
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PMID:Interleukin-2 restores the depressed allogeneic cell-mediated lympholysis and natural killer cell activity in patients with systemic lupus erythematosus. 315 17

Earlier studies from several laboratories showed that interferon-alpha (IFN-alpha) is present in the sera of a large percentage of patients with systemic lupus erythematosus (SLE). We now report the detection of IFN-alpha by indirect immunofluorescence in renal sections of three patients with SLE but not in six control kidneys. The immunofluorescence reaction was mediated by three hyperimmune antisera to IFN-alpha raised in three different species, but not by any preimmune serum. The reaction was specifically blocked by absorption of the anti-IFN-alpha sera with purified IFN-alpha made by recombinant DNA techniques or with IFN-alpha isolated from the serum of an SLE patient, but not by bovine serum albumin or human immunoglobulin G. In contrast, antisera to IFN-beta or IFN-gamma did not mediate immunofluorescence. The pattern of IFN-alpha deposition resembled that seen with anti-human immunoglobulin G, suggesting association with immune complexes. Immune complexes were then preparatively eluted from the homogenate of an SLE kidney by treatment with buffer at pH 2.8. Biologically active IFN was found in this eluate and was demonstrated to be IFN-alpha by specific neutralization with IFN antisera. These results extend the specific association of IFN-alpha with SLE.
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PMID:Renal deposition of alpha interferon in systemic lupus erythematosus. 641 15

The underlying immunopathogenic mechanism of CVID has been suspected to involve a chronic viral infection or an autoimmune condition. However, formal proof of viral infection is lacking. Measurement of MxA-protein in leucocyte lysates is a sensitive test for evaluating the activation of the host's interferon system. Both viral infections and autoimmune diseases such as systemic lupus erythematosus (SLE) strongly induce MxA-protein in peripheral leucocytes. We therefore examined 15 patients with longlasting hypogammaglobulinaemia for MxA-protein induction in vivo: 13 patients suffered from CVID, one from hyper-IgM syndrome, and one patient had chronic B lymphocytic leukaemia associated with immunoglobulin deficiency and chronic papilloma virus infection (condylomata accuminata). Only the latter patient exhibited a strong MxA-protein expression; two CVID patients were borderline positive, and the remaining 12 patients including the hyper-IgM syndrome were MxA-protein-negative. There was no relationship between MxA expression and low CD4/CD8 ratios or increased CD8/CD57+ T cell counts, although both conditions are often observed in CVID as well as in chronic viral infections. When exposed in vitro to interferon-alpha (IFN-alpha), peripheral blood leucocytes of four MxA-negative patients were capable of producing normal amounts of MxA-protein. Taken together, these results argue against a viral or autoimmune pathogenesis of CVID.
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PMID:Common variable immunodeficiency (CVID) and MxA-protein expression in blood leucocytes. 754 78

A number of drugs have recently been implicated in a syndrome that resembles systemic lupus erythematosus. One of the difficulties in many of these patients is that the signs, symptoms and serological abnormalities reported in these patients may be a natural consequence of the primary diseases rather than the incriminated drug. A second problem with the studies is a lack of uniform reporting of the techniques used to detect autoantibodies. For example, a patient that has a highly positive ANA with a homogeneous pattern of staining or a positive LE cell test usually has antibodies directed against chromatin components (DNA, histones, high mobility group (HMG) proteins). The discrepancies in clinical criteria and the serological techniques in many of these reports, emphasize the importance of using guidelines for the diagnosis of drug-induced or drug-related lupus. In the future, it appears that the increased use of biological response modifiers such as interferon-alpha and other cytokines may prompt more reports of lupus syndromes associated with their use.
Lupus 1994 Dec
PMID:Drugs recently associated with lupus syndromes. 770 1

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


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