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)

La (SS-B) protein is known as one major antigenic target for autoantibodies from patients with certain autoimmune diseases such as Sjogren's syndrome or Lupus Erythematosus. La protein belongs to the so called "extractable nuclear antigens". Here we report that La antigen is not restricted to the nucleus as one might deduce from the exclusive nuclear staining pattern of patient anti-La antibodies but after stimulation of serum-starved cells with 10% fetal calf serum (FCS) appears and stays for at least 45 min at the outer surface of CV-1 cells being available for binding of anti-La antibodies. In addition we found that a minor part of La antigen associates with the extracellular fibronectin network. After addition of 10% FCS to serum starved cells this extracellular autoantigen disassembled from the extracellular matrix and was taken up again by the cells. Incubation of serum starved cells with mercuric chloride, a known potent inducer of autoantibodies, also resulted in a detachment of the extracellular matrix associated La protein. From our studies it becomes likely that La protein itself is the antigen during autoimmunization. Moreover, once developed, anti-La antibodies might be able to bind to cell surface expressed La protein resulting in a damage of these cells leading to the inflammational events known to occur during disease.
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PMID:Translocation of the nuclear autoantigen La to cell surface: assembly and disassembly with the extracellular matrix. 171 61

U6 snRNA is a component of the major class of small RNA-protein complexes, the Sm snRNPs, present in mammalian cell nuclei. Here we report that a substantial fraction (about 10%) of U6 RNA from human and mouse cells is associated with another lupus antigen, the 50 kd La protein. The La-bound U6 subpopulation is characterized by 3' end heterogeneity and partial undermethylation. These U6 molecules have U-rich 3' termini that could be responsible for their selective association with the La protein. The question of whether they are precursors to the major U6 RNAs found in Sm snRNPs is discussed.
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PMID:Association of the lupus antigen La with a subset of U6 snRNA molecules. 258 64

The neonatal lupus syndromes, which comprise transient hematologic and cutaneous disorders as well as the permanent manifestation of heart block, are considered to result from injury by passively acquired maternal autoantibodies. The active placental transport of maternal IgG antibodies becomes operative late in the second trimester coincident with the time at which bradycardia and myocarditis become evident. Surprisingly there are no clinically detectable abnormalities in the maternal hearts. The recognition that antibodies to the SSA/Ro-SSB/La ribonucleoprotein complex were found in 85% of sera from mothers of offspring with neonatal lupus was an important advance and directed attention to these antigens as potential candidates despite their intracellular location. In the present review we describe an experimental approach to the treatment of a fetus diagnosed by in utero echocardiogram to have congenital complete heart block and to the prevention of this condition in an at-risk pregnancy. In an attempt to more specifically define the relevant antigen-antibody systems involved in the pathogenesis of neonatal lupus we have utilized the technique of immunoblot to evaluate sera from mothers of offspring with permanent manifestations of neonatal lupus including heart block and hepatic fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neonatal lupus and congenital complete heart block: manifestations of passively acquired autoimmunity. 269 Nov 58

The ribonucleoprotein (RNP) particles containing the Epstein-Barr virus-associated small RNAs EBER1 and EBER2 were analyzed to determine their RNA secondary structures and sites of RNA-protein interaction. The secondary structures were probed with nucleases and by chemical modification with single-strand-specific reagents, and the sites of modification or cleavage were mapped by primer extension. These data were used to develop secondary structures for the two RNAs, and likely sites of close RNA-protein contact were identified by comparing modification patterns for naked RNA and RNA in RNP particles. In addition, sites of interaction between each Epstein-Barr virus-encoded RNA (EBER) and the La antigen were identified by analyzing RNA fragments resistant to digestion by RNase A or T1 after immunoprecipitation by an anti-La serum sample from a lupus patient. Our results confirm earlier findings that the La protein binds to the 3' terminus of each molecule. Possible functions for the EBER RNPs are discussed.
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PMID:Structural analyses of EBER1 and EBER2 ribonucleoprotein particles present in Epstein-Barr virus-infected cells. 282 85

Several cDNA clones of the La antigen recognized by certain lupus autoantibodies were isolated from lambda gt11 expression libraries made from human liver. Recombinant clones were used to hybrid-select HeLa cell mRNA that was subsequently translated in vitro into a single protein species that comigrated with HeLa cell La protein. The in vitro translated protein was reactive with anti-La patient sera and was identical to the authentic La protein by peptide mapping. By analyzing overlapping cDNA clones, we mapped an antigenic site of La protein at the terminal 12% of the carboxyl end of the molecule. Within this region we identified a unique decapeptide of high hydrophilicity that may constitute a La antigenic determinant. We further demonstrated that the La antigen expressed from the recombinant clones can be used in a definitive enzyme-linked assay (ELISA) for the classification of sera from patients with systemic lupus erythematosus.
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PMID:Isolation and analysis of cDNA clones expressing human lupus La antigen. 385 88

Small ribonucleic acid (RNA)-protein complexes precipitated by anti-Ro and anti-La antibodies from lupus patients have been examined with emphasis on their RNA components. In both ribonucleoprotein (RNP) classes, the numbers of different RNA molecules and their sequences vary between mouse and human cells. The complex mixtures of La RNAs include two previously sequenced 4.5S RNAs from mouse cells and 5S ribosomal RNA-like molecules from both mouse and human cells. All Ro and La RNAs possess 5-triphosphates. Some La RNAs have internal modifications typical of transfer RNAs. The Ro RNPs are quite stable and are localized by immunofluorescence in the cell cytoplasm, whereas the majority of the La RNPs turn over rapidly and reside in the nucleus. Despite these differences, reconstitution experiments show that the Ro particles carry the La as well as the Ro determinant. Studies using a nuclear transcription system demonstrate that most of the La RNAs are synthesized by RNA polymerase III. The possibility that the La protein(s) functions in the transcription or maturation of all RNA polymerase III transcripts is discussed.
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PMID:Ro small cytoplasmic ribonucleoproteins are a subclass of La ribonucleoproteins: further characterization of the Ro and La small ribonucleoproteins from uninfected mammalian cells. 618 Feb 98

The La antigen recognized by certain lupus erythematosus autoantibodies was found to be predominantly associated with 7 S RNA in baby hamster kidney cells and human Raji cells, but not in HeLa cells where mainly the 7-2 RNA was associated with the La protein. In mouse myeloma cells (MPC-11) and mouse lymphoma cells (WEHI) that secrete immunoglobulins, equal amounts of 7 S and 7-2 RNAs were present in anti-La immunoprecipitates. The highly conserved 7 S RNA is a component of the signal recognition particle involved in protein secretion (Walter, P., and Blobel, G. (1982) Nature (Lond.) 299, 691-698), and its association with the La antigen appeared to be cell-type specific. Thus, it is possible that the La-7 S RNA association correlates with the abundance of 7 S RNA or with the secretory activity of the cell type.
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PMID:Association between the 7 S RNA and the lupus La protein varies among cell types. 619 54

The leader RNA transcript of vesicular stomatitis virus (VSV) has been immunoprecipitated from infected BHK cell extracts by anti-La specific sera from patients with systemic lupus erythematosus (SLE). This association was specific as lupus anti-sera with other specificities failed to precipitate leader RNA. The amount of leader RNA associated with the La antigen peaked 4 hr post infection and then declined. Leader RNA complexed with viral nucleocapsid proteins increased at a slower rate but eventually predominated 6 hr post infection. By 16 hr all of the leader RNA was associated with nucleocapsid proteins. Although a significant portion of the leader RNA was present in isolated nuclei 4 hr post infection, all of the leader RNA outside the nucleus was bound to La protein. Leader RNA is the first non-RNA polymerase III product found to associate with the La protein. The proposed function of the leader-La complex in VSV transcription and replication and in viral cytopathology is discussed.
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PMID:The leader RNA of vesicular stomatitis virus is bound by a cellular protein reactive with anti-La lupus antibodies. 631 10

Rabies virus leader RNA was detected in infected BHK-21 cell extracts by hybridization to end-labeled genomic RNA. Similar to the leader RNA of vesicular stomatitis virus, the leader RNA of rabies virus was also found to be associated with the La protein by specific immunoprecipitation with antisera from lupus patients. The 3' end of the genomic RNA of rabies virus was sequenced, and the size and termination site of leader RNA were determined. In addition, extension of the sequence into the nucleocapsid gene of rabies virus showed an open reading frame for at least 37 amino acid residues. Sequence relationships between rabies virus and vesicular stomatitis virus leader genes and the possible involvement of the La protein in rhabdovirus biology are discussed.
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PMID:Nucleotide sequence and host La protein interactions of rabies virus leader RNA. 632 6

Ro and La are intracellular ribonucleoproteins that are frequent targets for autoantibodies in the sicca syndrome and in lupus erythematosus. We analyzed the m.w. of the protein (antigen) moieties of Ro and La in saline cell extracts of human spleen by SDS-PAGE and immunoblotting, gel filtration, and sucrose density ultracentrifugation with radioimmunoassay. pI values for Ro and La proteins were established by isoelectric focusing on thin layer agarose gels and immunoblotting on nitrocellulose transfers. The La protein had an m.w. of approximately 43 kd and was heterogeneous in charge, with pI values from 4.2 to 4.8. Composite two-dimensional maps developed by immunoblotting revealed a characteristic set of seven dots of m.w. 43 kd. Ro determinants were identified on polypeptides of 50 and/or 57 kd. Antigenic activity was also detected in the void volume of spleen extract fractionated by Sephadex G-200 and in 8 to 9S and greater than 19S regions of sucrose gradients, suggesting either aggregation of the Ro protein or participation in protein-protein complexes. pI values of 4.3 to 5.5 were obtained for the Ro antigen, and two-dimensional maps revealed that the 57 kd polypeptide had a similar charge heterogeneity to the La protein, whereas the 50 kd polypeptide had a different fingerprint. Immunoblotting of extracts from bovine, rabbit, and dog extracts showed that antibodies to Ro and La reacted with a limited number of polypeptides (m.w. 50 and/or 57 kd for anti-Ro and 43 or 50 kd for anti-La). These studies support the physical independence of the isolated Ro and La polypeptides, although a precursor product or functional relationship in vivo is possible. These studies also suggest that, in addition to Western blotting, techniques involving immunodeletion, isoelectric focusing with capillary immunoblotting, and 2D immunoblotting provide useful approaches to characterize saline-soluble cellular antigens.
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PMID:Partial immunochemical characterization of the Ro and La proteins using antibodies from patients with the sicca syndrome and lupus erythematosus. 671 82


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