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)

In previous work, a murine monoclonal anti-DNA antibody (PME77) with specificity for double-stranded DNA has been found to bind five polypeptides (34, 33, 17, 16, and 14 kDa) that are expressed at the surface of several human cell types involved in lupus pathogenesis. To determine more precisely the nature of the antigens recognized by the PME77 monoclonal antibody, and to release cell-surface-accessible fragments, we used a mild, controlled elastase treatment. We isolated several of these polypeptides by immunoaffinity chromatography. A polyclonal antibody was prepared by immunizing a rabbit with a mixture of these polypeptides (17, 16, and 14 kDa) adsorbed on nitrocellulose. This antibody was shown to react with 17-, 16-, and 14-kDa polypeptides. This antibody does not bind to double-stranded DNA, suggesting that most of the immunogenic determinants of these polypeptides are not shared by double-stranded DNA. Of six human systemic lupus erythematosus sera tested, all contained antibodies that recognized this cell-surface protein(s) and crossreacted with double-stranded DNA. We suggest that this protein(s) be called LAMP [lupus-associated membrane protein(s)].
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PMID:Human systemic lupus erythematosus sera contain antibodies against cell-surface protein(s) that share(s) epitope(s) with DNA. 242 44

We recently demonstrated that a monoclonal anti-DNA antibody, spontaneously produced in lupus B/W mice, recognizes the same protein(s) at the surface of several human cell types involved in lupus pathogenesis including normal human erythrocytes, normal platelets and rat neuronal tissue. This cell-surface protein(s) cross-react(s) with double-stranded DNA. We suggest to call this protein(s) LAMP [lupus associated membrane protein(s)]. Here we show that: immunoglobulins eluted from kidneys of autoimmune MRL/lpr/lpr mice strongly react with LAMP. Anti-LAMP antibodies are present in large amount in MRL/lpr and B/W mice sera. Anti-LAMP are present in 25 out of 25 human SLE sera ranged as SLE on the basis of revised American Rheumatism Associated classification. Interestingly, two of these sera did not display anti DNA anti-body activity. Taken together, these results strongly suggest a role of LAMP in the pathogeny of SLE.
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PMID:[Pathogenic antibodies in systemic lupus erythematosus: anti-LAMP antibodies]. 309 42

A murine monoclonal anti-DNA antibody, PME77, with specificity for double-stranded DNA, has previously been shown to react with a protein(s) present at the surface of such cells involved in lupus pathogenesis as human glomeruli, T and B lymphocytes, erythrocytes, and platelets. Mild elastase treatment of lymphoid cells from non-autoimmune (CBA/ca or BALB/c) mice releases a series of crossreactive polypeptides (34, 33, 17, 16, and 14 kDa) recognized by PME77. These polypeptides are not formed after treatment of the same cells with papain or trypsin. When lymphoid cells from autoimmune [MRL-lpr/lpr or (NZB X NZW)F1 B/W] mice are treated with elastase, trypsin, or papain, PME77 detects, in all supernatants, a single polypeptide of about 55 kDa. Antibodies present in the sera of autoimmune MRL-lpr/lpr and B/W mice and IgG eluted from kidneys of MRL-lpr/lpr mice react with the same polypeptides. Neither sera nor eluted IgG of normal BALB/c mice react with these polypeptides. These results suggest that an altered cell-surface protein(s), which we call LAMP [for lupus-associated membrane protein(s)], may be involved in lupus pathogenesis.
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PMID:Altered cell-surface protein(s), crossreactive with DNA, on spleen cells of autoimmune lupic mice. 346 72

Anti-double-stranded (ds) DNA autoantibodies are considered as pathogenic in systemic lupus erythematosus (SLE). Anti-DNA antibodies have been shown to be released by B cells from lupus mice or patients in vitro. A monoclonal anti-DNA antibody (PME 77) specific for dsDNA has previously been shown to react with a cell-surface protein called LAMP (lupus-associated membrane protein), which is present on the cell surface of various cell types involved in SLE pathogenesis. Using an immunoreplica analysis technique, we show here that spleen cells from MRL/Mp-lpr/lpr lupus mice, cultured in vitro, spontaneously produce anti-LAMP IgG antibodies. Conversely, anti-LAMP antibodies were not detected in spleen-cell culture supernatants from nonautoimmune CBA/Ca mice. Taken together with our previous reports, this result adds a new argument for a pathogenic role of anti-LAMP autoantibodies in SLE.
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PMID:Splenocytes from MRL/Mp-lpr/lpr mice spontaneously produce antibodies against a cell-surface protein cross-reacting with DNA. 367 91

Rt6 is a T cell-restricted GPI-anchored membrane protein and a member of the family of mono(ADP-ribosyl)transferases. One of the two murine Rt6 genes is deleted in NZW mice. This finding is reminiscent of the deletion of one of the TCR beta genes in the same mouse strain and it is an intriguing possibility that these gene deletions arose by a common genetic mechanism. The Rt6 locus retained by the NZW mouse (designated Rt6-1) is polymorphic among inbred strains of laboratory mice. The NZW mouse shows several strain-specific restriction fragment length variants in this Rt6 locus and five amino acid substitutions occur in the predicted native Rt6 polypeptide of the NZW mouse relative to the corresponding polypeptides of NZB and BALB/c mice. Whereas transcript levels of the two Rt6 genes appear to be normal in spleen and intestine of NZB mice, the corresponding tissues of NZW mice show reduced levels of transcripts from the Rt6 locus retained in this mouse strain. Moreover, reduced levels of Rt6 mRNA also occur in spleen and intestine of (NZB x NZW)F1 hybrid animals, indicating that F1 animals have inherited a dominant factor from the genetic background of the NZW mouse, resulting in low levels of Rt6 expression. It is conceivable that the alterations in the Rt6 genes of the NZW mouse and/or the factor(s) affecting defective Rt6 expression constitute part of the genetic contribution of the NZW mouse to the autoimmune lupus-like disease in (NZB x NZW)F1 animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Defects in the structure and expression of the genes for the T cell marker Rt6 in NZW and (NZB x NZW)F1 mice. 754 15

Endothelial cells form a multifunctional cell lining that covers all of the inner surface of blood vessels and regulates several important physiological and pathological reactions. These include inflammation/immune reaction, blood vessel tonus, hemostasis/thrombosis, angiogenesis and so on. Thus, abnormalities of endothelial function may play crucial roles in the development of angitis syndrome, thrombosis/embolism, bleeding disseminated intravascular coagulation (DIC), and neovascularization in some pathological states including tumor growth and diabetic retinopathy. Research on endothelial cells now forms a new frontier termed 'Endotheliology'. Recent advances of the functional and structural aspects of endothelial cells are reviewed here mainly from the viewpoint of endothelial regulation of coagulation and the fibrinolytic system. First we show that the natural endothelial membrane protein thrombomodulin is localized not only on apical endothelial surface but also in caveolae. Since it has been reported that such factors involved in coagulation/fibrinolysis as tissue factor, tissue factor pathway inhibitor (TFPI), thrombin receptor and urokinase receptor are also localized in the caveolae, this membrane structure may act as a special component to regulate coagulation/fibrinolysis on the endothelial membrane surface. Next we demonstrate the signaling pathway of the thrombin receptor. Thrombin cleaves the N-terminus of the receptor as a substrate, exposing a new N-terminus. This newly exposed N-terminus acts as a ligand and activates platelets, endothelial cells and vascular smooth-muscle cells. We have identified that the signal from the thrombin receptor activates NF-kappaB through the activation of protein C kinase, tyrosine kinase and MAP kinase, and results in proliferation of the cells. We have also shown that the receptor is over-expressed on platelets from diabetes patients.
Lupus 1998
PMID:Biology of endothelium. 981 71

Autoantibodies to EEA1 have been described in patients with neurological diseases, subacute cutaneous lupus and a variety of other conditions, including a patient with Wegener's granulomatosis (WG). EEA1 is a hydrophilic peripheral membrane protein transiently associated with the cytoplasmic face of early endosomes. Antibodies to EEA1 produce a staining pattern that resembles the C-ANCA pattern produced by anti-proteinase 3 (PR3) antibodies in WG sera. Co-localization studies show incomplete overlap of the staining produced by anti-EEA1 with anti-PR3. We showed that 0/40 unselected sera, from a cohort of WG patients and antibodies to PR3, reacted with EEA1. In addition, 1/15 sera that have a C-ANCA staining pattern but do not react with PR3 in an ELISA, immunoprecipitated the recombinant EEA1 protein. We conclude that although antibodies to EEA1 produce a staining pattern that resembles anti-PR3 and C-ANCA, antibodies to EEA1 in WG are rare. However, some C-ANCA+ sera that do not react with PR3 may contain EEA1 autoantibodies.
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PMID:Autoantibodies to early endosome antigen (EEA1) produce a staining pattern resembling cytoplasmic anti-neutrophil cytoplasmic antibodies (C-ANCA). 1112 60

Fibroadenomas are the most common benign tumors of the female breast and are associated with a slight increase in the risk of subsequent breast cancer. Multiple fibroadenomas have been described in patients after renal transplantation and are thought to be secondary to drug-related growth stimulation. Epstein-Barr virus (EBV) has been detected in many neoplasms, including breast cancer. We set out to investigate whether EBV plays a role in the development of rapidly growing fibroadenomas in immunocompromised patients. We studied 19 fibroadenomas and one invasive ductal carcinoma that developed after organ transplantation or treatment for lupus erythematosus. As a control group we included 11 fibroadenomas from non-immunocompromised patients. DNA was amplified using polymerase chain reaction (PCR) of the EBV-encoded small RNA (EBER-2) DNA sequence. EBV latent membrane protein 1 (LMP-1) transcripts were amplified using reverse transcription (RT) PCR. Immunohistochemical (IHC) staining for LMP-1 protein was performed. A total of 9 out of 20 tumors (45%) were concordantly positive by PCR and IHC. IHC stained exclusively the epithelial cells. All the fibroadenomas in non-immunocompromised patients were negative for LMP-1 (Fisher's exact test P =.0006). These data suggest that EBV is associated with fibroadenomas in this immunosuppressed population and that the infection is specifically localized to epithelial cells. This is the first study suggesting a role for EBV in the pathogenesis of fibroadenomas.
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PMID:Detection of Epstein-Barr virus in rapidly growing fibroadenomas of the breast in immunosuppressed hosts. 1211 14

Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that mainly acts as an inhibitor of immune functions. A lack of functional TGF-beta leads to autoimmune disease in animal models and dysregulated TGF-beta signaling is implicated in human autoimmune diseases. To define target genes that play a part in the inhibitory role of TGF-beta in the immune system, we have identified genes stimulated by TGF-beta in macrophages by gene-chip analysis. One of the TGF-beta regulated genes is carboxypeptidase D (CpD), a 180-kDa type I membrane protein. We have demonstrated that CpD is regulated by TGF-beta in various cell types of both, murine and human origin and, interestingly, is significantly downregulated in CD14 positive cells isolated from patients with lupus erythematosus (LE). Moreover, we show that downregulation of CpD leads to downmodulation of TGF-beta itself, suggesting a role for CpD in a positive feedback loop, providing further evidence for a role of this enzyme in LE. To our knowledge, this is the first report that demonstrates carboxypeptidase D as a TGF-beta target gene that is implicated in the pathogenesis of LE.
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PMID:Carboxypeptidase D: a novel TGF-beta target gene dysregulated in patients with lupus erythematosus. 1764 57

Epstein-Barr virus (EBV) is a human herpesvirus hiding in a latent form in memory B cells in the majority of the world population. Although, primary EBV infection is asymptomatic or causes a self-limiting disease, infectious mononucleosis, the virus is associated with a wide variety of neoplasms developing in immunosuppressed or immunodeficient individuals, but also in patients with an apparently intact immune system. In memory B cells, tumor cells, and lymphoblastoid cell lines (LCLs, transformed by EBV in vitro) the expression of the viral genes is highly restricted. There is no virus production (lytic viral replication associated with the expression of all viral genes) in tight latency. The expression of latent viral oncogenes and RNAs is under a strict epigenetic control via DNA methylation and histone modifications that results either in a complete silencing of the EBV genome in memory B cells, or in a cell-type dependent usage of latent promoters in tumor cells, germinal center B cells, and LCLs. Both the latent and lytic EBV proteins are potent immunogens and elicit vigorous B- and T-cell responses. In immunosuppressed and immunodeficient patients, or in individuals with a functional defect of EBV-specific T cells, lytic EBV replication is regularly activated and an increased viral load can be detected in the blood. Enhanced lytic replication results in new infection events and EBV-associated transformation events, and seems to be a risk factor both for malignant transformation and the development of autoimmune diseases. One may speculate that an increased load or altered presentation of a limited set of lytic or latent EBV proteins that cross-react with cellular antigens triggers and perpetuates the pathogenic processes that result in multiple sclerosis, systemic lupus erythematosus (SLE), and rheumatoid arthritis. In addition, in SLE patients EBV may cause defects of B-cell tolerance checkpoints because latent membrane protein 1, an EBV-encoded viral oncoprotein can induce BAFF, a B-cell activating factor that rescues self-reactive B cells and induces a lupus-like autoimmune disease in transgenic mice.
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PMID:Regulation and dysregulation of Epstein-Barr virus latency: implications for the development of autoimmune diseases. 1843 10


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