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)

SS-B antigen was purified from fresh rabbit thymus by ammonium sulfate precipitation and column chromatography with Sephadex G100 and phosphocellulose. The M. W. of SS-B is ranged at 41,000 to 48,000. It does not contain the other extractable antigens, like Sm, RNP, PM-ScL, Scl-70, Jo-1, and PCNA. The purified SS-B antigen only reacts with the CDC standard serum of anti-SS-B antigen only reacts with the CDC standard serum of anti-SS-B antibody by ELISA. The positive rate of the antibodies being 55.1%, 48.3%, 32.8%, 30.8% and 26.3% in SS, SLE, RA, PSS and MCTD respectively. The titers of anti-SS-B antibodies were higher in SS and SLE patients than other connective tissue disease patients. It was found that all of the anti-SS-B antibodies detected were mainly of IgG isotype. Preliminary analysis of clinical date shows that there is no relationship between anti-SS-B antibody and systemic involvement in SS.
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PMID:[The purification of SS-B antigen and detection of anti-SS-B antibodies]. 840 25

Autoantibodies to ribosomal P proteins (anti-P) are detected almost exclusively in the serum samples from patients with systemic lupus erythematosus when conventional enzyme-linked immunosorbent assay and immunoblotting techniques are used. Anti-P are not detected in serum samples from healthy adults by these techniques. By treating serum from healthy adults with ribosome-coated beads, we unexpectedly unmasked anti-P in virtually all individuals. This unmasking of anti-P occurs by the displacement of an antibody inhibitor from anti-P. We wanted to determine whether anti-P from healthy adults could also be unmasked by treatment of their serum or plasma with isolated ribosomal P proteins. Recombinant human ribosomal P2 protein was produced in bacteria as a TrpE fusion protein, resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, blotted onto nitrocellulose membranes, and isolated as strips of membranes corresponding to the size of the P2 fusion protein. Serum or plasma from six healthy adults and three patients with systemic lupus erythematosus were incubated with these strips overnight rather than for 2 hours, as is done in conventional immunoblots. Acid eluates were obtained from the strips and analyzed for antibody activity by immunoblot. Eluates from healthy adults and patients contained antibodies reactive with recombinant ribosomal P2 protein. They also reacted with the three ribosomal P proteins in purified rabbit ribosomes. Their anti-P activity was completely inhibited by a peptide corresponding to the immunodominant linear epitope of the ribosomal P proteins. The antibodies in the eluate were immunoglobulin G. We conclude that anti-P autoantibodies from healthy adults can be unmasked by affinity purification on denatured, recombinant ribosomal P proteins and that antigen excess is sufficient for inhibitor displacement.
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PMID:Recombinant ribosomal P2 protein can unmask anti-ribosomal P autoantibodies from healthy adults. 865 35

Antiphospholipid antibodies, including anticardiolipin antibodies (ACA), are strongly associated with recurrent thrombosis in patients with the antiphospholipid syndrome (APS). To date, reports about the binding specificities of ACA and their role(s) in causing and/or sustaining thrombosis in APS are conflicting and controversial. The plasmas of patients with APS, usually containing a mixture of autoantibodies, vary in binding specificity for different phospholipids/cofactors and vary in in vitro lupus anticoagulant activity. Although in vivo assays that allow assessment of the pathogenic procoagulant activity of patient autoantibodies have recently been developed, the complex nature of the mixed species prevented determination of the particular species responsible for in vivo thrombosis. We have generated two human IgG monoclonal ACA from an APS patient with recurrent thrombosis. Both bound to cardiolipin in the presence of 10% bovine serum, but not in its absence, and both were reactive against phosphatidic acid, but were nonreactive against purified human beta-2 glycoprotein 1, DNA, heparan sulfate, or four other test antigens. Both monoclonal autoantibodies lacked lupus anticoagulant activity and did not inhibit prothrombinase activity. Remarkably, one of the monoclonal antibodies has thrombogenic properties when tested in an in vivo mouse model. This finding provides the first direct evidence that a particular antiphospholipid antibody specificity may contribute to in vivo thrombosis.
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PMID:A monoclonal IgG anticardiolipin antibody from a patient with the antiphospholipid syndrome is thrombogenic in mice. 871 Sep 18

The purpose of this study is to determine whether immunoadsorption treatment using a dextran sulfate (DS) column can remove high-avidity anti-double-stranded DNA (anti-dsDNA) antibody from the blood of patients with systemic lupus erythematosus (SLE). Before and after each immunoadsorption therapy routine, titers of the high-avidity anti-dsDNA antibody of 11 SLE patients were measured by using a newly developed assay kit to exclusively detect high avidity anti-DNA antibody. Patients with active SLE showed significantly higher titers of high-avidity antibody than did those with inactive SLE, and their titers were significantly reduced by immunoadsorption procedures. Removal of high-avidity antibodies in vitro was also confirmed by mixing patients' sera and DS gel. Immunoadsorption therapy using DS columns is effective in the removal of high-avidity anti-dsDNA antibodies that are closely associated with pathogenicity in SLE.
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PMID:High-avidity anti-DNA antibody removal from the serum of systemic lupus erythematosus patients by adsorption using dextran sulfate cellulose columns. 872 20

It has been suggested that binding of anti-double-standed DNA antibodies to cell surfaces, followed by internalization and nuclear binding (so called in vivo ANA) is of pathophysiological significance for tissue damage in systemic lupus erythematosus. We have shown before that pathogenic antinuclear antibodies complexed to nucleosomal antigens can bind to heparan sulfate in the glomerular basement membrane in vivo. Because nucleosomes are also reported to bind to the cell surface, we hypothesized that in vivo ANA is a property of antinuclear antibodies bound to nucleosomal antigens. Therefore, we studied three antinucleosome monoclonal antibodies (mAb) that exhibit in vivo ANA as seen by immunofluorescence in mice inoculated intraperitoneally with the hybridoma producing the mAb. The same mAb complexed to nucleosomal antigens after intravenous injection into mice induced in vivo ANA, in contrast to purified noncomplexed mAb. To study this in more detail, we incubated complexed mAb with various cell lines and found binding to the cell surface and subsequent internalization into cytoplasmic vesicles. However, no binding to the nucleus was observed by immunoelectron microscopy (IEM) and confocal laser microscopy. Noncomplexed mAb did not bind to the cell surface. Next, from mice bearing the hybridomas producing the mAb intraperitoneally, a small part of the kidney was snap frozen in liquid N2, fixed with acetone, and studied in immunofluorescence, whereas the remaining part of the kidney was fixed in vivo by renal perfusion with a mixture of 0.01 M sodium periodate, 0.075 M lysine HCl, 0.0375 M Na2HPO4, and 2% paraformaldehyde (PLP) and studied in both immunofluorescence and IEM. In the acetone-fixed kidney sections obtained without in vivo fixation we again observed in vivo ANA. However, after in vivo PLP perfusion fixation, no nuclear binding was found. In IEM, localization in cytoplasmic vesicles was seen. In conclusion, antinucleosome antibodies complexed to nucleosomal antigens can bind to the cell surface and are transported into the cytoplasm, but do not bind to the nucleus. The reported nuclear localization of antinuclear antibodies is caused by a fixation artifact.
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PMID:In vivo ANA is a fixation artifact: nucleosome-complexed antinucleosome autoantibodies bind to the cell surface and are internalized. 879 5

Heparin and heparan sulfate are related glycosaminoglycans which demonstrate high-affinity interactions with a number of proteins, including antithrombin III. The immunogenicity of heparin has been reported previously employing heparin-protein conjugates as immunogens and as antigens in solid-phase assays. Previous studies also demonstrate that anti-heparin antibodies play a role in autoimmune diseases including systemic lupus and anti-phospholipid syndrome and in patients who receive heparin for therapeutic purposes. In the current study, we investigated the expression of monoclonal anti-heparin antibodies in nonimmunized, autoimmune MRL/lpr/lpr++ mice employing a liquid-phase radioimmunoassay. The Kd of monoclonal IgG2b autoantibodies for heparin was approximately 10(-8)M. Anti-heparin antibodies were precipitating, and were not polyreactive. The IgG monoclonal antibodies described in this study represent an immunological instance of a specific, high-affinity heparin-protein interaction.
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PMID:Autoimmune MRL mice express high-affinity IgG2b monoclonal autoantibodies to heparin. 880 43

Reactivity of serum antibodies with heparan sulfate (HS) has been associated with human and murine lupus nephritis, although the aetiological significance of this association is not clear. Recent work from our laboratories showed that binding of these antibodies to HS could be mediated by histone containing immune complexes. In human lupus nephritis we found a strong decrease in HS staining in the glomerular basement membrane (GBM). The aim of this study was to elucidate the correlation in experimental systemic lupus erythematosus (SLE) between albuminuria, staining of HS in the GBM and anti-DNA and anti-HS reactivity in plasma. We therefore studied NZB/W F1 mice during different stages of glomerular disease and compared them with age matched control NZB/W F1 mice without albuminuria. Anti-DNA and anti-HS reactivity were measured in longitudinally collected plasma samples and correlated with the onset of albuminuria, staining of HS in the glomerular basement membrane and deposition of immunoglobulins (Ig). HS staining was significantly decreased in the glomerular capillary loops of mice with prolonged proteinuria in comparison with age matched control mice (P = 0.0013). This decreased HS staining was correlated with increased Ig deposition in the capillary loops (tau = -0.42, P < 0.001), albuminuria (tau = -0.508, P < 0.001) and a decreased in anti-DNA levels measured in plasma (tau = 0.758, P < 0.005). Altered anti-HS reactivity in plasma did correlate with increased Ig deposition in the kidney (tau = 0.33, P < 0.05) but was not correlated with decreased staining of HS in the kidney. In conclusion, our study demonstrates that disappearance of staining of HS in the glomerular capillary loops is associated with albuminuria, increased Ig deposition in the glomerulus and decreased anti-DNA reactivity in plasma. Our findings are compatible with a model in which interaction ('masking') of HS with immune complexes consisting of anti-DNA antibodies and nucleosomes takes place.
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PMID:Heparan sulfate staining of the glomerular basement membrane in relation to circulating anti-DNA and anti-heparan sulfate reactivity: a longitudinal study in NZB/W F1 mice. 884 53

Autoantigen-reactive T cells might play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Autoantigen-reactive T cell clones were generated from spleens of NZB x NZW F1 (BWF1) and normal control BALB/c mice with interleukin-2 (IL-2), a procedure that selects for in vivo activated antigen-reactive T cells. The antigen-specificity of the T cell clones was tested by using a panel of candidate autoantigens. The T cell clones from BWF1 mice but not those from BALB/c mice proliferated against heparan sulfate, the major glycosaminoglycan of glomerular basement membrane. None of the clones proliferated against dsDNA or cardiolipin. All the heparan sulfate-reactive T cell clones had the ability to selectively augment the production of IgG anti-dsDNA autoantibodies. When cultured with either heparan sulfate or Concanavalin A, the T cell clones produced high levels of IL-4 and IL-5 with no detectable IL-2 or IFN-gamma. In contrast, T cell clones derived from BALB/c mice augmented the production of total polyclonal IgG but not the production of anti-dsDNA antibodies. These studies indicate the existence of heparan sulfate-reactive T cells in BWF1 mice. Characterization of heparan sulfate-reactive T cells that could selectively augment anti-dsDNA production will permit the design of targeted and antigen-specific therapy.
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PMID:Isolation and functional characterization of IL-2 responsive T cell clones from NZB x NZW F1 mice. 893 77

Levels of anti-dsDNA measured just after an immunoadsorption procedure in systemic lupus erythematosus (SLE) patients are sometimes paradoxically larger than those measured just before the procedure. A 1:100 in vitro single-compartment immunoadsorption system model was devised to determine which of two models, one- or two-compartment, more closely approximates the kinetics of anti-dsDNA during apheresis procedures. Ten SLE patients were employed in this study. A total of 4,100 ml of plasma was passed through the dextran sulfate cellulose columns during one clinical apheresis session. In eight of ten patients, the log of RIA-measured anti-dsDNA titers decreased linearly as treated plasma volume increased, in both the clinical procedure and the experimental model. The mean adsorption efficacy in the clinical apheresis procedure and in the in vitro model was 0.37 and 0.27, respectively. However, in one patient the RIA-measured level of anti-dsDNA increased during the apheresis procedure; this phenomenon was mirrored in the model (definitely a single pool model). In contrast, the level of anti-dsDNA, as measured by ELISA, decreased in accordance with the increase of treated plasma volume in both the clinical and the in vitro apheresis procedures. Therefore, an increased titer of anti-dsDNA as measured by RIA immediately following clinical apheresis cannot be accounted for exclusively by an inflow of antibodies from a secondary (extravascular) pool into the circulating plasma. In short, a one-compartment model is applicable and an explanation must be sought elsewhere.
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PMID:Anti-dsDNA antibody kinetics during in vivo apheresis in systemic lupus erythematosus patients and in an in vitro apheresis model. 898 67

Programmed cell death, an essential function in all cells, plays a central role in maintaining immune system homeostasis and controlling autoimmune reactions. Cell death may be an essential element in disseminated lupus erythematosus: defective cell death could lead to the development of autoreactive lymphocyte clones and degradation products of cell death could be implicated in autoimmunity induction and onset of renal lesions. Anomalies in programmed cell death have been demonstrated in murine models of lupus: mutations of the fas and fas-ligand genes, which play a known role in programmed cell death, produce the lpr and gld phenotypes associating lymphoproliferation and lupus. Transgenic mice which express Bcl-2 (the product of Bcl-2 inhibits programmed cell death) on B lymphocytes develop a lupus-type autoimmune disease. The role of these types of anomalies in human disease is not yet elucidated. However, cell death, via the degradation fragments of chromatin, could play a role in inducing antibody production and development of renal lesions. The anti-DNA antibodies, with characteristic antigen-induced immune response (clone expansion, class computation and somatic mutations) could be induced by nucleosomes released during cell death. Several arguments favor this mechanism including cation residues of histone nucleosomes which would bind to anionic residues of sulfate heparan and lead to deposit of autoantibodies in the glomerulus. The dual role of cell death is not really contradictory in autoimmune disease controlled by several independent genes, but would be compatible with several different genetic backgrounds.
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PMID:[Cell death and lupus]. 909 57


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