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 immunological basis for the production of autoantibodies characteristic of systemic lupus erythematosus (SLE) against a wide range of antigens remains obscure. The specificity of (NZB x NZW)F1 (BWF1) or MRL/Mp-lpr/lpr (MRL/lpr) mouse monoclonal antibodies (mAb) was examined by immunofluorescence, immunoblotting and immunoprecipitation techniques. Using non-synchronized HEp-2 cells as substrate, the murine mAb were classified by indirect immunofluorescence into five groups on the basis of their staining patterns of subcellular components in interphase and mitotic stages of the cell cycle. The nature of the antigens recognized by the murine lupus was assessed by immunoblotting experiments in total, cytoplasmic and nuclear cell extracts from HEp-2 cells. The six antibodies used recognized in total cell extracts a range of polypeptides with apparent molecular weights from 25,000 to 210,000. Three polypeptides of 130,000, 110,000 and 45,000 MW were recognized by all six antibodies in both nuclear and cytoplasmic extracts. Immunoprecipitation of total cellular extracts labelled with [35S]methionine showed almost the same pattern as obtained in the immunoblotting assay. The labelling in vivo of HEp-2 cells with [32P], followed by the immunoprecipitation of the [32P]cell lysate showed that these mAb recognized phosphorylated proteins. The progressive decrease in reactivity of these mAb following treatment with higher concentrations of alkaline phosphatase in both [32P]cell lysate or nitrocellulose membranes indicates that these mAb recognize phosphorylated epitopes.
 ...
PMID:Systemic lupus erythematosus murine monoclonal DNA-binding antibodies recognize cytoplasmic and nuclear phosphorylated antigens that display cell cycle redistribution in HEp-2 cells. 128

Antibodies to Su antigen have been reported previously as a distinct antigen-antibody system associated with connective tissue diseases; most specifically systemic lupus erythematosus and undifferentiated connective tissue disease. The Su antigen was first identified by double immunodiffusion using calf thymus nuclear extract (CTNE) as a source for Su antigen. In this report, enhanced extraction of Su antigen was achieved using deoxyribonuclease I (DNase) for preparation of CTNE. Only the Sm antigen was found in comparable quantities in the DNase CTNE. Western immunoblotting and immunoprecipitation employing DNase CTNE and extracts of [35S]methionine-labeled HeLa cells respectively were used for further characterization and differentiation of the Su antigen. Sera from patients positive for Su antibodies by double immunodiffusion were found to react most specifically with antigen components in a molecular weight range of approximately 50-55 kDa. These methods should assist in further understanding the biochemical properties of the Su antigen.
 ...
PMID:Extraction and differentiation of the Su autoantigen from calf thymus nuclei. 191 22

SS-B/La is a conserved cellular phosphoprotein of 46 to 48 KD that is the target antigen of autoantibodies in sera of patients with Sjogren's syndrome and systemic lupus erythematosus. SS-B/La is also known to be associated with certain small cellular and viral RNA, including adenovirus VAI and VAII RNA. Two relatively protease-resistant domains (X and Y) were defined in SS-B from HeLa cells by using human autoantibodies as reagents. Domain X, a methionine-containing nonphosphorylated 28 KD polypeptide, was found to be resistant to partial digestion with six different proteases. Similar domains were also found in calf and rabbit SS-B. Domain Y, a 23 KD polypeptide, was detected after limited digestion with S. aureus V8 and trypsin. This domain contained little if any methionine, but all the detectable phosphorylated amino acids. Among 16 anti-SS-B sera tested by immunoblotting, 11 (69%) were reactive with both domains, three (19%) only with domain X, and two (13%) only with domain Y. These results showed that there are at least two distinct antigenic epitopes on the 46 to 48 KD SS-B/La protein, each located on a separate structural domain. The asymmetric distribution of methionine and phosphorylated amino acid residues in SS-B/La show striking similarity to the two reported domains of the adenovirus 72 KD DNA-binding protein, and raises questions concerning functional similarities that await investigation.
 ...
PMID:Epitopes, structural domains, and asymmetry of amino acid residues in SS-B/La nuclear protein. 242 60

We studied the possible role of polymorphonuclear neutrophil (PMN) aggregation in Systemic Lupus Erythematosus (SLE) by the capacity of sera from 32 lupus patients to induce in vitro normal PMN aggregation. Neutrophil aggregating activity (NAA) in this group was significantly greater than that found in 8 inactive SLE patients and in 8 controls. In patients with SLE, there was a positive correlation between disease severity and the quantitative measure of NAA. High levels of NAA were particularly characteristic of central nervous system SLE. These data suggest that the formation of intravascular leukoaggregates may contribute to morbidity in SLE. Normal PMN increase their spontaneous superoxide anion production (0.21 nmol/min 10(7) PMN) when stimulated with sera from SLE patients. Lupus PMN also show an enhancement of 100% in superoxide production in vitro when stimulated with lupus sera. When N formyl methionine leucyl phenylalanine (FMLP) was used, lupus PMN showed an O2-production of 2.1 nmol/min 10(7) which is 5-fold the response of normal PMN stimulated by FMLP. Our results show the existence of seric factors in SLE patients that can stimulate O2-production by PMN. Lupus neutrophils show an increased response to membrane stimuli such as FMLP, capable of triggering the respiratory burst. Lupus neutrophils appear more responsive membrane stimuli such as FMLP, capable of triggering the respiratory burst. Lupus neutrophils appear more responsive to membrane stimuli. The seric and the cellular factors seem to indicate an increased rate of superoxide production by PMN in SLE patients, which can be relevant to vasculitis and tissue damage.
 ...
PMID:[Neutrophil-dependent inflammatory reactions in systemic lupus erythematosus]. 264 Apr 79

Autoantibodies found in approximately 15% of patients with systemic lupus erythematosus recognize three 60 S ribosomal phosphoproteins P0, P1, and P2. Fab fragments obtained from sera of these patients inhibited globin mRNA translation in an in vitro protein synthesizing system which was reversed by the addition of excess ribosomes. Further studies suggested that these antibodies bind to ribosomes in the intact cell. Thus, when IgG fractions from these sera were microinjected into cultured human fibroblasts [35S]methionine incorporation into cellular proteins was inhibited.
 ...
PMID:The inhibition of protein synthesis by IgG containing anti-ribosome P autoantibodies from systemic lupus erythematosus patients. 319 35

We have screened sera from patients with systemic lupus erythematosus for reactivity with RNA transcribed in vitro using HeLa whole cell extracts. Sera from 14 out of 114 patients precipitated an RNA transcribed by RNA polymerase III from a plasmid containing an Alu family sequence (i.e. the repetitive DNA sequence that is cut by the Alu restriction enzyme) located upstream from the human gamma G-globin gene. These Alu transcripts were not precipitated by anti-La, anti-Sm, anti-RNP or anti-Ro antibodies, suggesting that Alu RNA was precipitated by a previously undescribed lupus specificity. Analysis of [35S]methionine-labeled immunoprecipitates indicated that Alu RNA binds a protein of about 68 kDa. This protein may be Alu specific since three different Alu transcripts were precipitated by the anti-Alu sera whereas another RNA polymerase III transcript, adenovirus VA I RNA, was not precipitated by the same sera.
 ...
PMID:Alu RNA-protein complexes formed in vitro react with a novel lupus autoantibody. 404 79

The platelet binding properties of human monoclonal lupus autoantibodies have been studied. These IgM autoantibodies, produced by human X human hybridomas derived from lymphocytes of patients with systemic lupus erythematosus, are known to bind to single-stranded DNA. Four anti-DNA antibodies that express the dominant 16/6 idiotype--HF2-1/17, HF2-18/2, HF2-1/13b, and HF3-16/6--bound to glutaraldehyde-fixed platelets. In contrast, HF6-21/28, HF9-11/3, and polyclonal IgM bound poorly to platelets. [35S]Methionine was incorporated into HF2-1/17, and the interaction of the intrinsically radiolabeled HF2-1/17 with fixed platelets was evaluated in a solution phase radioimmunoassay. [35S]Methionine HF2-1/17 bound to fixed platelets and could be displaced by equivalent amounts of HF2-1/17, HF2-18/2, HF2-1/13b, and HF3-16/6. HF2-1/17 bound with greater affinity to fresh platelets and to thrombin-activated platelets than to glutaraldehyde-fixed platelets. Single-stranded DNA competed with platelets for the HF2-1/17 combining site. Treatment of fresh platelets with nuclease I, trypsin, chymotrypsin, and neuraminidase did not alter the binding of antibody to the platelet surface. No binding of antibody to phospholipid micelles was observed. Purified IgM autoantibodies did not inhibit platelet aggregation induced with ADP, thrombin, or ristocetin in platelet-rich plasma. These results indicate that the human IgM monoclonal anti-DNA autoantibodies that express the dominant 16/6 idiotype are polyspecific, bind to platelets, and interact with a platelet epitope that does not appear to involve DNA, protein, or sialic acid. These antibodies interact with platelets through the same sites responsible for antibody-DNA binding.
 ...
PMID:Platelet binding properties of monoclonal lupus autoantibodies produced by human hybridomas. 406 19

The activity of phospholipase inhibitory protein, lipomodulin, partially purified from rabbit neutrophils, was markedly decreased after treatment with sera from patients with rheumatic diseases such as systemic lupus erythematosus, rheumatoid arthritis, and dermatomyositis. The decrease of the protein's inhibitory activity on phospholipase A2 paralleled the amount of [35S]methionine-labeled lipomodulin precipitated by the sera. Absorption of patients' sera with anti-human IgM (mu chain) or protein A-agarose, but not with anti-human IgG (gamma chain), decreased their ability to decrease the activity of lipomodulin on phospholipase A2 or to precipitate the radioactive lipomodulin. The IgM fraction of patients' sera could precipitate [35S]methionine-labeled lipomodulin (40,000 daltons) which comigrated with highly purified lipomodulin on gel electrophoresis with sodium dodecyl sulfate. All of these observations suggest that the sera of many patients with rheumatic diseases contain autoantibody against lipomodulin. A monoclonal antibody against lipomodulin was also obtained. Stimulating human fibroblasts with bradykinin in the presence of monoclonal antilipomodulin antibody markedly enhanced arachidonic acid release due to the activation of phospholipase(s) in the intact cells, and this stimulatory effect was blocked by adding purified lipomodulin. These findings suggest that lipomodulin regulates the activity of phospholipase(s) on the cell surface and that autoantibodies against lipomodulin may play a role in certain symptoms of rheumatic diseases, especially by the formation of prostaglandins and other metabolites of arachidonic acid.
 ...
PMID:Presence of autoantibody for phospholipase inhibitory protein, lipomodulin, in patients with rheumatic diseases. 611 91

Immunoprecipitation of human small nuclear ribonucleoproteins (snRNPs) containing the small nuclear RNAs U1, U2, U4, U5, and U6 with two antibodies produced in certain patients suffering from systemic lupus erythematosus was used to identify the polypeptides present on human U1 and U2 snRNPs. U1 and U2 snRNPs contain both common and unique polypeptides; visualization of the differences was possible through the use of non-methionine protein labeling and partial fractionation of snRNP populations. To facilitate comparisons with results from other laboratories, we have designated the snRNP polypeptides by their molecular weights. Four small polypeptides, P8, P9, P10, and P12, of 8,000 to 12,000 daltons, are each present in equal amounts on both U1 and U2 snRNPs. U1 snRNPs also contain a unique 30,000-dalton polypeptide, P30, whereas U2 snRNPs contain a unique 27,000-dalton, methionine-deficient polypeptide, P27. A closely migrating pair of polypeptides, P23 and P22, of 23,000 and 21,500 daltons, respectively, is present on both snRNPs; U2 snRNPs are enriched in the former, and U1 snRNPs are enriched in the latter.
 ...
PMID:Human U1 and U2 small nuclear ribonucleoproteins contain common and unique polypeptides. 618 8

Antibodies directed against small nuclear ribonucleoprotein ( snRNP ) particles are found in the Sm and RNP autoimmune sera from numerous patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). These two reactivities differ in disease distribution as well as antigen specificity. Although sera from both of these autoimmune syndromes contain snRNP reactive antibodies, distinction in antigen binding specificity have been difficult to define because of the particulate nature of the snRNP antigen. To overcome this problem, while retaining the antigen in a native state, cells were pulse-labeled with [35S]methionine for 8 min to generate radioactive snRNP proteins in forms reflecting incomplete de novo particle assembly. Immunoprecipitation of snRNP antigen prepared in this manner revealed clearly distinct patterns of Sm and RNP immunorecognition . While Sm sera precipitated all eight labeled snRNP proteins, RNP antibodies precipitated only two of the eight. However, a brief pulse followed by periods of cold chase demonstrated that RNP sera can eventually coprecipitate all components of the complete particle. In addition to antibodies to the other six snRNP peptides, all Sm sera tested have been found to contain the RNP-like reactivity with snRNP proteins A and C. RNP reactivity with these two components is of particular interest because these proteins are unique in the metabolism of snRNPs. Defining and distinguishing the precise peptides recognized by Sm and RNP antibodies has helped to clarify the biochemical basis of the standard laboratory tests for these antigen reactivities.
 ...
PMID:Pulse labeling of small nuclear ribonucleoproteins in vivo reveals distinct patterns of antigen recognition by human autoimmune antibodies. 620 15


1 2 3 4 Next >>