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)

Some disease manifestations are associated with serum antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE) in what has been termed antiphospholipid syndrome (aPLS). There are patients with aPLS who do not have SLE or any other illness who have been grouped under the term primary antiphospholipid syndrome (PAPS). However, patients with diverse infections, notably syphilis, may have aPL but do not develop the associated clinical manifestations. This has been attributed, at least in part, to the immunochemical features of their aPL, including the requirement for beta 2-glycoprotein-I (beta 2GP-I) for binding of aPL to phospholipids, but these have not been studied in sera from patients with PAPS. By ELISA we studied 95 sera from 17 patients with PAPS and 100 sera from clinically normal individuals for IgG and IgM antibodies to the main anionic and zwitterionic phospholipids and their related compounds, phosphatidic acid (PA) and synthetic phosphorylcholine (PRC). beta 2GP-I was present, either in newborn calf serum (NBCS) or purified, to block wells and to dilute samples, or was substituted by 0.3% gelatin. Inhibition studies with phospholipid micelles were used to confirm reactivities with the corresponding phospholipids. All 17 patients had IgG and 11 had IgM antibodies to cardiolipin. Antibodies to anionic phospholipids were primarily IgG whereas those to zwitterionic phospholipids were mainly, and often exclusively, IgM. We found a statistically significant difference in the mean levels of antibodies to all anionic phospholipids except aPTS, and to the haptene PA (P < 0.001) between patients and controls. The difference between levels of IgM antibodies to zwitterionic phospholipids was statistically significant with sphingomyelin (P < 0.001) and the haptene (P < 0.001). Levels of most IgG and most IgM aPL correlated significantly among them. The pattern and titers of reactivity are variable between patients, but stable within each patient. Requirement of beta 2GP-I for this reactivity was not an all-or-nothing phenomenon in individual sera. In general, as in lupus sera, antibodies to anionic phospholipids require that this cofactor be present coating the ELISA plates, whereas those to zwitterionic phospholipids do not. It would appear that patients with PAPS have polyclonal mixtures of antibodies that react with various phospholipids and have different requirements for beta 2GP-I for such reactivity.
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PMID:Phospholipid specificity and requirement of beta 2-glycoprotein-I for reactivity of antibodies from patients with primary antiphospholipid syndrome. 148 89

An ELISA technique for the detection of anti-beta 2 glycoprotein I (beta 2gp I) antibodies was developed. Among 47 systemic lupus erythematosus patients, 17 had anti-beta 2gp I antibodies. These antibodies were statistically associated with anticardiolipin antibodies, lupus anticoagulant and thrombosis. Out of 18 patients with anticardiolipin antibodies without anti-beta 2gp I antibodies or lupus anticoagulant, only one had thrombosis (due to nephrotic syndrome). Therefore the presence of anti-beta 2gp I antibodies is a new immunologic marker of lupus patients with thrombosis. In addition, we propose that anti-beta 2gp I antibodies may be directly responsible for lupus anticoagulant activity.
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PMID:[Anti-beta 2 glycoprotein I antibodies in systemic lupus erythematosus: a marker of thrombosis associated with a circulating anticoagulant]. 178 67

Glucocorticoids induce dramatic biochemical and morphological changes in lymphocytes through an unknown process that requires RNA and protein synthesis. In order to identify genes involved in this response, we previously isolated 11 cDNA clones from the murine WEHI-7TG thymoma cell line that correspond to mRNAs induced by glucocorticoids. We now report the isolation of two new cDNA clones whose gene expression is regulated by glucocorticoids in WEHI-7TG cells. We further characterize the two new cDNA clones, as well as those described previously, by examining the response of each of the corresponding mRNAs to glucocorticoids in murine thymocytes. With the exception of two, all cDNAs correspond to genes that are induced by glucocorticoids in murine thymocytes within 4 h of treatment. We previously identified two of the cDNAs as the mouse VL30 retrovirus-like element and the mouse homolog of chondroitin sulfate proteoglycan core protein. We have now identified four additional cDNA clones that correspond to the genes for calmodulin, mitochondrial phosphate carrier protein, immunoglobulin (Ig)-related glycoprotein (GP-70), and the 70 kilodalton autoantigen for Lupus and Graves diseases. Two other cDNA clones represent previously undescribed genes: one shares a high similarity to known sequences for the family of G-protein-coupled receptors and the other to a human placental-specific protein, PP11. Another cDNA appears to contain sequences for an unknown gene and the remnants of a mouse transposon. ETn. The remaining clones represent new, unidentified genes induced by glucocorticoids in murine thymocytes and in the WEHI-7TG cell line.
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PMID:Genes newly identified as regulated by glucocorticoids in murine thymocytes. 207 23

In vivo therapy with monoclonal antibody (mAb) GK1.5, which recognizes a glycoprotein antigen designated L3T4 on murine helper T lymphocytes, either prevented or suppressed the development of murine lupus, autoimmune encephalomyelitis, and collagen arthritis. The L3T4 antigen in the mouse is analogous to the human Leu-3/T4 antigen expressed on helper T lymphocytes, because they both participate in the T cell response to class II major histocompatibility complex (MHC) antigens. Class II MHC genes and I-A antigens mediate murine experimental autoimmune myasthenia gravis (EAMG) induced by acetylcholine receptor (AChR) autoimmunity. We studied the efficacy of mAb GK1.5 as an immunotherapeutic agent for murine EAMG. Therapy with mAb GK1.5 not only suppressed established autoimmunity to AChR but also prevented loss of muscle AChR in mice with EAMG. Moreover, permanent remission of clinical muscle weakness was induced if mAb GK1.5 therapy was initiated after the onset of clinical disease. Because the function of the Leu-3/T4 determinant on human helper T lymphocytes is analogous to the murine L3T4 determinant, use of antibody to the Leu-3/T4 determinant as an immunotherapeutic agent may provide a way to control the progression of human MG.
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PMID:Immunotherapy for myasthenia gravis: a murine model. 241 35

MRL/1 mice, reported by Murphy and Roths, are lupus mice in which monogenic mutation has occurred. They are characterized by the expression of massive lymphoadenopathy, splenomegaly, arthritis and glomerulonephritis. These specific characters are attributable to the proliferation of abnormal T cells governed by an autosomal recessive gene, which is called a lymphoproliferative (lpr) gene. In this study, the author has studied the pathology of various organs in MRL/1 mice in relation to their ages. Investigated the pathogenesis of spontaneous submaxillaritis in MRL/1 mice and mechanism of its occurrence. Based on the immunological abnormalities in MRL/1 mice studied thus far, the mechanism of onset of submaxillaritis is believed to be as follows; (1) expression of the lpr gene leads to proliferation of T cells accompanied by focal lymphocyte infiltration in the submandibular gland; (2) the helper T function of these proliferating T cells induces polyclonal B cell activation (PBA); (2) PBA leads to the formation of numerous autoantibodies and anti-gp70 antibody whose antigen is the glycoprotein of endogenous retrovirus, resulting in the massive formation of immune complexes; (4) the immune complexes are deposited on the vascular wall, resulting in activation of the complement system; (5) infiltration of neutrophils and macrophages is induced; and (6) the lysosomal enzymes, released from these cells, effects as a cytotoxic mediator and damages the vascular wall. In brief, submaxillaritis accompanied by granulomatous vasculitis can be regarded as a Type III allergic response caused by immunological abnormalities which are genetically determined by the lpr gene; it is thought to be a subtype of immune complex disease.
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PMID:[Immunohistochemical study of the submaxillaritis in MRL/1 mouse (lymphoproliferation and autoimmunity)]. 253 61

Antiplatelet autoantibodies are important in the etiology of idiopathic (or immune) thrombocytopenic purpura (ITP). Studies using immunoblotting techniques have been helpful in identifying the antigenic target proteins for the antibodies. Antibodies against the glycoprotein (GP) IIIa portion of the GPIIb/IIIa complex were the first to be demonstrated by this approach. Similar GPIIIa autoantigens have also been found to be the most frequent targets of ITP antibodies. Not all anti-GPIIIa antibodies are directed against the same epitope on GPIIIa. A subset of anti-GPIIIa antibodies found in patients with an acquired qualitative platelet dysfunction actually interfere with fibrinogen binding to normal platelets. Antibodies directed against targets on GPV have been found in patients with acute ITP of childhood. In patients with ITP associated with lupus erythematosus, antibodies which bind to intracellular proteins of apparent molecular weights of 66 and 108 kDa have been detected. Thus, ITP antibodies can have a variety of target antigens. Study of larger series of patients will determine whether identification of platelet autoantigens correlates with clinical course of ITP.
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PMID:Platelet autoantigens: identification and characterization using immunoblotting. 275 75

Naturally occurring thymocytotoxic autoantibodies (NTA) have been described in both humans and mice with SLE. To define further the role of anti-thymic autoantibodies in murine lupus, we studied the cellular and molecular specificity of a spontaneous monoclonal NTA, designated TC-17, derived from a 4-mo-old New Zealand Black mouse. TC-17, an IgM autoantibody, has been shown previously to be unreactive with Lyt-1, Lyt-2, and L3T4 (T helper) antigens. We have shown further that it is also unreactive with Thy-1. TC-17 recognizes a new thymic antigen that appears to mark a distinct subpopulation of cortisol-sensitive cortical thymocytes. The antigen consists of a single glycoprotein chain with an apparent m.w. of 88,000. TC-17 shows reduced binding to thymocytes treated with tunicamycin, indicating either that glycosylation of TC-17 antigen is necessary for TC-17 to bind to it or that glycosylation is required for expression of the antigen on the cell surface. TC-17 uniquely reacts with two of 17 murine lymphoid tumor cell lines of intermediate cellular maturity. The thymocytotoxic activity of TC-17 is absorbed by single cell suspensions of murine stomach, small intestine, large intestine, kidney, and thymus. Moreover, the specific binding of TC-17 to gut tissue of normal and germfree mice can be demonstrated by indirect immunofluorescence, suggesting antigenic cross-reactions between thymic and gut tissue. TC-17 reacts with rat thymocytes as well as it does with murine cells, indicating moderate evolutionary conservation of the TC-17 antigen. The expression of this glycoprotein by a discrete thymocyte subset may prove to be a valuable probe for the study of murine T cell differentiation.
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PMID:Tissue localization and biochemical characteristics of a new thymic antigen recognized by a monoclonal thymocytotoxic autoantibody from New Zealand black mice. 392 16

This study demonstrated that 88% of untreated systemic lupus erythematosus patients with clinical renal disease displayed the deposition of immunoglobulin and complement at the dermal epidermal junction of the noninvolved light exposed extensor surface of the upper 1/3 of the forearm (P less than 0.005) (positive lupus band test). Eighty-five percent of these untreated systemic lupus erythematosus patients with anti-deoxyribonucleic acid antibodies (native and/or single stranded) (P less than 0.001) and 96% of systemic lupus erythematosus patients with hypocomplementemia had a positive lupus band test (P less than 0.001). Those systemic lupus erythematosus patients with a negative lupus band test or a positive lupus band test composed of pure IgM had a decreased incidence of renal disease, serum hypocomplementemia and anti-DNA antibodies. Their sera, however, frequently contained antibodies directed against nuclear ribonuclear protein or against the cytoplasmic non-nucleic acid glycoprotein termed Ro. On the contrary, 85% of systemic lupus erythematosus patients with a positive lupus band test composed solely or in part of IgG, had anti-DNA antibodies (P less than 0.001). Their sera also frequently contained anti-Sm antibodies. The lupus band test was found to be dynamic. In general, the appearance as well as the disappearance or the marked decrease in intensity and complexity of a positive lupus band test was found to correlate with disease exacerbation, remission and the appearance and disappearance of DNA antibodies and serum hypocomplementemia.
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PMID:Lupus band test in untreated SLE patients: correlation of immunoglobulin deposition in the skin of the extensor forearm with clinical renal disease and serological abnormalities. 696 66

Simultaneous studies of serum and urinary proteins in 294 adult proteinuric patients are presented. Our data showed that these studies can provide valuable guides for clinical diagnosis. In the group of idiopathic nephrotic syndrome, hypoalbuminemia, hypogammaglobulinemia and hyper-alpha 2 globulinemia were most marked. Urinary protein electrophoresis (PEP) showed a well-selective pattern with albumin and beta globulin as the main constituents. In the other groups of proteinuric patients the hypoalbuminemia and hyper-alpha 2 globulinemia were milder and urinary PEP generally showed non-selective pattern. In the groups of acute glomerulonephritis and lupus nephropathy, C3 was generally decreased; polyclonal gammopathy was frequently encountered and alpha 1 acid glycoprotein was markedly increased. In the cases of chronic glomerulonephritis and diabetic nephropathy and the levels of gamma globulin, C3 and alpha 2 acid glycoprotein were usually within normal limits. Urinary protein selectivity index in this series of adult patients was not a useful diagnostic parameter.
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PMID:Simultaneous studies of serum and urinary proteins for evaluation and diagnosis of glomerular damages in proteinuric patients. 722 87

The effect of dietary restriction on the expression of retroviral envelope glycoprotein, gp70, and the formation of gp70-anti gp70 immune complexes was investigated in lupus-prone NZB x NZW F1 hybrid mice. Restricting total calorie intake from the usual 20 to only 10 calories per day after weaning markedly reduced serum levels of both free and antibody-complexed gp70, prevented renal disease, and increased the life spans of these mice. The reduction in serum gp70 was evident after only 2 wk of feeding these animals the low-calorie diet, and the concentration remained virtually unchanged throughout the course of 10 mon experimentation. However, serum concentrations of the major structural protein, p30, of endogenous retroviruses were not altered by restricting calories. Amounts of the serum glycoprotein, haptoglobin, decreased parallel to those of gp70 but amounts of albumin did not. These results suggest that the expression of gp70 in serum is controlled independently of the production of complete viral particles, and regulated by a mechanism similar to that for other serum glycoproteins, such as haptoglobin.
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PMID:Low-calorie diet selectively reduces expression of retroviral envelope glycoprotein gp70 in sera of NZB x NZW F1 hybrid mice. 728 64


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