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)

The degree of complement activation produced by hydrogen peroxide was estimated by the inhibition of serum homolytic activity (% IHA). Sera from patients with systemic lupus erythematosus and psoriasis vulgaris were resistant to hydrogen-peroxide-mediated complement activation. %IHA negatively correlated with ceruloplasmin level or catalase activity in systemic lupus erythematosus sera, but did not correlate with transferrin level. The addition of free metal ions, FeCl2 or CuCl2, promoted hydrogen-peroxide-mediated complement activation. These results suggest that hydroxyl radical is involved in complement activation and that the factors responsible for the insensitivity of pathological sera to H2O2 are catalase and ceruloplasmin in the sera. Human skin fibroblasts generate superoxide and tumor necrosis factor enhanced it, but interleukin-1 beta inhibited it. Normal serum cultured with fibroblasts for 24 h showed complement activation via catalase-inhibitable process, suggesting that hydrogen peroxide has an important role in fibroblast-mediated complement activation. It is speculated that fibroblasts and complement activation by oxygen radicals have an important role in inflammation and subsequent tissue damage at the site of skin lesion.
 ...
PMID:Possible role of H2O2-mediated complement activation and cytokines-mediated fibroblasts superoxide generation on skin inflammation. 255 Feb 83

The nature and distribution of mononuclear cells in non-ulcerated oral lesions of discoid (DLE) and systemic lupus erythematosus (SLE), were investigated and compared to other chronic inflammatory oral diseases (lichen planus (LP), contact lesion (CL), unspecified inflammation (UI), geographic tongue (GT), and leukoplakia (LK). For this purpose an immunoperoxidase technique based on staining with monoclonal antibodies was employed. In most LE specimens examined infiltrating cells consisted predominantly of a mixture of T cells (Leu 3a+ and Leu 2a+) that were distributed in the lamina propria, the submucosa, and occasionally also in the epithelium. In general, only few B cells were detected while macrophages were more frequent. In all LE specimens examined beta 2-microglobulin expression was observed on a large proportion of cells including infiltrating mononuclear cells as well as resident keratinocytes. In addition, most infiltrating cells displayed MHC Class II antigens according to a pattern HLA-DR greater than DQ greater than DP. Interestingly, expression of Class II antigens was also observed on epithelial keratinocytes but was restricted to HLA-DR and -DP gene products (DR much greater than DP). HLA-DQ expression was never observed on keratinocytes. In most LE specimens studied a small proportion (less than 5%) of inflammatory cells had detectable interleukin-2 receptors (IL-2R) and/or transferrin receptors (transf-R). However, expression of transf-R was also observed on basal epithelial cells, being more pronounced in DLE than in SLE lesions. The above staining patterns observed in LE lesions, when compared to other chronic inflammatory oral lesions, did not disclose any striking differences that could support the specific diagnosis of LE. However, the findings of Class I and II MHC gene products on oral keratinocytes suggest an important accessory role for these cells in directing the migration of activated lymphoid cells in the epithelium in chronic inflammatory lesions of the oral mucosa.
 ...
PMID:Oral lesions of lupus erythematosus patients in relation to other chronic inflammatory oral diseases: an immunologic study. 306 Sep 88

The presence of various antibodies in serum samples from patients with systemic lupus erythematosus (SLE) and from healthy subjects was investigated by ELISA, using a panel of natural antigens. Fifty-eight serum samples from 58 healthy women and 50 serum samples from 30 patients with active SLE were tested with 9 natural antigens (ds-DNA, actin, tubulin, thyroglobulin, myosin, myoglobin, human transferrin, human interferon a and BSA FV). It was found that the proportion of positive sera from healthy women at a dilution of 1/20 was almost the same as that of lupus sera at a dilution of 1/150 for nearly all antigens, while at a dilution of 1/150 the proportion of positive sera from patients with SLE was significantly higher for nearly all antigens. In lupus sera a high degree of correlation was observed between titers of anti-DNA and titers of the other antibodies. One hundred eighty-eight serum samples from 53 SLE patients, taken during exacerbation and remission of the disease were tested with ds-DNA, actin and tubulin. Antibodies (IgG) to ds-DNA actin and tubulin were found in the majority of serum samples taken during the active phase of the disease. On the other hand, very few serum samples taken during remission were found to be positive. A high degree of correlation was found between the OD of anti-actin/anti-ds-DNA (r = 0.769) and anti-tubulin/anti-ds-DNA (r = 0.829). In a competitive enzyme immunoassay for DNA, actin, tubulin, myosin and thyroglobulin, a high degree of inhibition was observed with the homologous antigens.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Autoantibodies in systemic lupus erythematosus and normal subjects. 378 Jan 41

A lupus-like disease characterized by a severe immune complex glomerulonephritis and IgG autoantibody production was induced in (C57BL/6 X DBA/2)F1 mice by injection of parental DBA/2 lymphoid cells. The ensuing graft-vs-host (GVH) reaction resulted in a 10- and a 100-fold increase in serum IgG antibody levels to denatured DNA and total histones, respectively, compared with that in F1----F1 control mice. The level of anti-DNA antibodies peaked 2 wk after injection of DBA/2 cells and preceded peak anti-histone levels by approximately 2 wk. Anti-histone antibodies were generated predominantly to histones H1, H2A, and H2B, a profile different from that observed in NZB/NZW and MRL-lpr/lpr mice. The marked increase in IgG antinuclear antibodies did not correlate with increases in total IgG serum levels and was not associated with comparable increases in antibodies to transferrin, hemoglobin, fibrinogen, or thyroglobulin. Selective autoantibody production was also observed in vitro, wherein GVH spleen cells produced high levels of IgG antibodies to total histones and denatured DNA but not to these non-nuclear protein antigens. In contrast, spleen cells stimulated in vitro with lipopolysaccharide produced equivalent amounts of antibodies to all antigens tested. Our results are in agreement with those of other investigators and collectively suggest that IgG autoantibodies in GVH disease, and possibly in spontaneous lupus-like disease, are not secondary to a generalized B cell activation, but may be selectively generated in response to self antigens with unique configurational properties.
 ...
PMID:Autoimmunization in murine graft-vs-host disease. I. Selective production of antibodies to histones and DNA. 387 58

The autoantibodies found in human and murine systemic lupus erythematosus (SLE) are generally directed against cells or components of cells such as nuclear antigens. This predilection may be due to the unusual immunogenicity of certain autoantigens, or to unusual patterns of antibody crossreactivity. Alternatively, the observed spectrum of reactivities may reflect the in vivo absorption of those autoantibodies directed against soluble antigens. To test whether hitherto undetected autoantibodies against serum proteins might exist in murine SLE, we developed assays that were independent of the possibility of absorption of autoantibodies by serum autoantigens; large numbers of plaque-forming cells (PFC) directed against mouse albumin and mouse transferrin were easily detected in the spleens of MRL/Mp-lpr/lpr, BXSB, and NZB mice. The secreted antibodies were relatively specific for the mouse proteins, since only limited cross-reactivity was seen with albumin and transferrins of other species in inhibition experiments. The production of these hidden antibodies could not be the result of diffuse polyclonal B cell activation, since the PFC to mouse transferrins and albumin were not always accompanied by comparable numbers of PFC against related albumins and transferrins. The results indicate that autoantibody production in murine lupus is a generalized phenomenon, not limited to the production of autoantibodies to nuclear or other cell-bound antibodies. However, the relative specificity of the autoantibodies for self-antigens indicates that diffuse polyclonal B cell activation cannot be the mechanism responsible, and argues that a selective mechanism, probably driven by antigen, accounts for production of autoantibodies in SLE.
 ...
PMID:Hidden autoantibodies against common serum proteins in murine systemic lupus erythematosus. Detection by in vitro plaque-forming cell assay. 404 Jan 53

In addition to previously described cold-reactive IgM anti-lymphocyte antibodies maximally cytotoxic for resting cells at 15 degrees C, sera from patients with systemic lupus erythematosus (SLE) were found to contain a new type of antibody preferentially reactive at physiologic temperatures with mitogen-activated lymphocytes. This antibody lacked specificity for unstimulated lymphocytes, and was shown to be of the IgG class both by indirect immunofluorescence and in immunochemical experiments. Certain SLE sera also contained IgG antibodies with the capacity to develop plaques with mitogen-activated T lymphocyte preparations used in a reverse hemolytic plaque assay, indicating reactivity with products released by activated cells. The elimination of the ability of SLE sera to develop plaques after absorption with viable mitogen-stimulated lymphocytes, but not with resting cells, suggested that these antibodies were directed toward activation "neoantigen(s)" shed from the cell surface membrane. Surface membrane phenotype analyses performed by using a variety of monoclonal antibody reagents indicated that the plaque-forming cells (PFC) detected with SLE sera were activated T lymphocytes not restricted to single OKT4+, OKT8+, or Ia antigen+ subpopulations. Essentially all PFC expressed transferrin receptors. The present data raise the possibility that certain of the interesting effects of anti-lymphocyte antibodies on immunologic function in SLE may be mediated by interactions of these new type(s) of antibodies with activated lymphocytes or their products, rather than through blocking or depletion effects on resting precursor cells.
 ...
PMID:Characterization of warm-reactive IgG anti-lymphocyte antibodies in systemic lupus erythematosus. Relative specificity for mitogen-activated T cells and their soluble products. 660 Jan 74

The intraglomerular presence of thrombomodulin (TM) was examined in 19 patients with lupus glomerulonephritis (GN). TM is a cell surface glycoprotein found on endothelial cells and plays a key role in the protein C anticoagulant pathway. Renal biopsy specimens of patients with lupus GN and several kinds of renal disease other than lupus GN, i.e., membranous GN, IgA GN, minimal change nephrotic syndrome (MCNS) and hemolytic uremic syndrome (HUS) were examined by indirect immunofluorescence, using three kinds of monoclonal antibodies against human TM: KA-2, KA-3 and KA-4. It has been reported that KA-3 and KA-4 bind to enzyme-digested TM as well as intact TM, while KA-2 recognizes intact TM only. In the glomeruli from both normal subjects and patients with MCNS, only very weak staining of TM was found. Patients with HUS showed negative TM staining in the glomeruli. In contrast, positive to strongly positive staining of KA-2 as well as of KA-3 and KA-4 was observed mainly along the capillary wall of glomeruli from patients with lupus GN. Some patients with non-lupus GN showed positive staining of these monoclonal antibodies, but the staining was far more intense in most patients with lupus GN than in the patients with non-lupus GN. Staining of albumin and transferrin by the indirect method was negative in all cases of lupus GN that showed positive staining of TM. There was no relationship between the intensity of TM staining and the degree of proteinuria, creatinine clearance or histologic types of lupus GN.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Enhanced presence of thrombomodulin in the glomeruli of lupus glomerulonephritis. 802 12

A 79-year-old native American female with a history of diabetes mellitus, but no history of hepatic or renal disease, presented with anasarca and hypoalbuminemia. Laboratory tests for fecal alpha 1-antitrypsin and an indium III-labeled plasma transferrin nuclear scan revealed a protein-losing enteropathy. A serological test was positive for antinuclear antibody in a titer of 1:1250 with a homogeneous pattern. This finding combined with low normal serum complement levels suggested the diagnosis of systemic lupus erythematosus (SLE). This case is unusual in that protein-losing enteropathy was the only presenting symptoms. The late onset of this disease is also unusual.
 ...
PMID:Primary lupus-associated protein-losing enteropathy. 804 95

Somatic gene therapy is an interesting approach for the delivery of cytokines for prolonged periods. The present experiments show that direct injections into mouse skeletal muscle of cDNA expression vectors encoding interleukin 2 (IL-2), IL-4, or type beta 1 transforming growth factor (TGF-beta 1) induce biological effects characteristic of these cytokines in vivo. Mice injected intramuscularly with a vector encoding IL-2 had enhanced humoral and cellular immune responses to an exogenous antigen, transferrin, that was delivered at a separate site. These IL-2 effects were abolished by coadministration of a vector directing synthesis of TGF-beta 1. The TGF-beta 1 vector by itself depressed the anti-transferrin antibody response and caused an 8-fold increase in plasma TGF-beta 1 activity. The TGF-beta 1 plasmid injection did not cause muscle infiltration with monocytes or neutrophils and there was no evidence for fibrotic changes. Muscle injection with a cDNA encoding IL-4 selectively increased IgG1 levels but did not alter the cellular immune response to transferrin. In lupus-prone mice (MRL/lpr/lpr), injection with IL-2 expression vectors increased and TGF-beta 1 vectors decreased auto-antibodies to chromatin. These results demonstrate that intramuscular injection of cytokine genes, in the absence of infectious viral vectors, can regulate humoral and cellular immune responses in vivo.
 ...
PMID:Systemic immunological effects of cytokine genes injected into skeletal muscle. 850 93

Soluble transferrin receptors (sTfR) were detected in culture supernatants of activated human peripheral blood mononuclear cells (PBMC) using a sandwich ELISA technique with two non-cross-reacting TfR MoAbs. Mitogenic stimulation of lymphoid cells induced both up-regulation of TfR surface density and release of sTfR to the medium. Peak levels of sTfR in culture supernatants occurred at day 4 after activation, 1 day later than maximum expression of TfR in the plasma membrane. Production of sTfR was independent of proliferation, as demonstrated by measuring sTfR release by PBMC, which had been irradiated with a dose of 20 Gy before activation. In addition to these in vitro experiments, we tested the sera of 85 patients with systemic lupus erythematosus (SLE), an autoimmune disease accompanied by in vivo activation of lymphocytes, for their sTfR levels. No correlation of these data was detectable to serum concentrations of the soluble alpha-chain of the IL-2 receptor, an unequivocal marker of lymphocyte activation. However, they correlated negatively to the haemoglobin content of the patients' erythrocytes, indicating that erythroid progenitors are the predominant source of sTfR in SLE patients' sera.
 ...
PMID:A soluble form of the human transferrin receptor is released by activated lymphocytes in vitro. 851 87


<< Previous 1 2 3 4 Next >>