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)

Patients with systemic lupus erythematosus often possess antibodies against two nuclear antigens called Sm and RNP (ribonucleoprotein). We have established the molecular identity of these antigens by analyzing immune precipitates of nuclear extracts from mouse Ehrlich ascites cells labeled with (32)P and (35)S. Anti-Sm serum selectively precipitates six small nuclear RNA molecules (snRNAs); anti-RNP serum reacts with only two of these; and a third serum, characterized as mostly anti-RNP, precipitates a subset of three snRNA bands. Three of the six RNAs are identified by fingerprint analysis as the previously characterized and highly abundant nucleoplasmic snRNA species U1a (171 nucleotides), U1b, and U2 (196 nucleotides). The other three RNAs (U4, U5, and U6) likewise are uridine rich and contain modified nucleotides, but they are smaller, with lengths of about 145, 120, and 95 residues, respectively. Each of the six snRNAs is complexed with and apparently antigenic by virtue of association with specific proteins. All three sera precipitate an identical complement of seven different polypeptides ranging in molecular weight from 12,000 to 35,000; these proteins are abundant in nuclear extracts, but are neither histones nor the major polypeptides comprising the 30S heterogeneous nuclear RNP particles of mammalian nuclei. Our data argue that each of the six snRNAs exists in a separate small nuclear ribonucleoprotein (snRNP) complex with a total molecular weight of about 175,000. We find that human antisera also precipitate snRNAs from a wide range of vertebrate species and from arthropods. We discuss the antigenic snRNPs in relation to the published literature on snRNAs and nuclear RNPs and consider possible functions of snRNPs in nuclear processes.
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PMID:Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus. 31 37

The Sm-D(D1) small nuclear ribonucleoprotein (snRNP) polypeptide is a major target of autoantibodies diagnostic for systemic lupus erythematosus. The cDNA encoding the protein from Raji cells was expressed in Escherichia coli as a fusion protein with anthranilate synthase (TrpE-Sm-D). When tested by protein blot, the recombinant polypeptide was strongly immunoreactive under defined blotting conditions, which appear to facilitate the refolding of the polypeptide into a native conformation. Multiple translational fusions between the trpE gene and fragments encompassing the length of the Sm-D coding sequence were constructed for epitope mapping. The results describe two general patterns of anti-Sm reactivity: (i) antibodies that recognize only the full-length antigen and are presumably directed against discontinuous epitopes, and (ii) antibodies that recognize the carboxy terminus of the antigen which embodies an extended/charged structure.
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PMID:Mapping of the immunoreactive domains of a small nuclear ribonucleoprotein-associated Sm-D autoantigen. 128 May 41

Proteins from U1 and U2 small nuclear ribonucleoprotein (snRNP) particles, which are common targets of autoantibodies found in some rheumatic diseases, were analysed for the presence of glycans. A glycan detection assay revealed that the U1-specific proteins 68K and A and the U2-specific protein B" are glycosylated. However, none of the Sm proteins, which are common to all the major snRNP particles, showed a detectable level of glycosylation. With the use of specific lectins, an analysis of the particular carbohydrate(s) attached to the U1 snRNP 68K protein demonstrated the presence of at least one N-linked oligosaccharide chain. Lectin detection of galactose, glucose, mannose and N-acetylglucosamine on 68K was confirmed by chemical analysis of the carbohydrates. The glycopeptide nature of these antigens may be important for understanding the role of autoantigens in the pathogenesis of autoimmune disorder.
Lupus 1992 Feb
PMID:Small nuclear ribonucleoprotein particles contain glycoproteins recognized by rheumatic disease-associated autoantibodies. 130 63

The spatial organization of two rheumatic disease-associated epitopes and the RNA "cap" structure of the U1 small nuclear ribonucleoprotein (snRNP2) was analyzed both in situ and in vitro by two independent interference immuno-assays. Sm and RNP autoantibodies, associated with systemic lupus erythematosus and mixed connective tissue disease, respectively, were used to probe the epitope locations. The Sm epitope on the U1 snRNP structure was localized proximal to the RNP. Experiments with an anti-m7G (mRNA "cap") monoclonal antibody revealed that an in situ association of the Sm and RNP epitopes with the mRNA "cap" structure may exist. Our findings, together with previous observations by others, suggest a model for the spatial arrangement of these rheumatic disease-associated protein epitopes, and the U1 RNA within the U1 snRNP particle.
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PMID:Spatial localization of distinct rheumatic disease-associated epitopes and the RNA "cap" of the U1 snRNP particle. 137 34

Antibodies to the Sm nuclear antigen are diagnostic of systemic lupus erythematosus (SLE). MRL/Mp-lpr/lpr mice develop a similar illness, and a proportion also develop anti-Sm. To understand better anti-Sm reactivity in this murine model, we have cloned the murine Sm-D autoantigen. One cDNA clone was 517 bp long with an open reading frame of 357 nucleotides, encoding a 13.3 kDa protein of 119 amino acids. At the nucleotide level, the murine Sm-D cDNA was 89.8% homologous with human Sm-D (94% in the coding region), yet there was identity at the protein level, including a Gly-Arg nine-fold repeated C-terminus motif. Southern blot analysis of PstI-digested genomic DNA from seven mouse strains demonstrated a 7.8 kb band in every strain; in addition, a 2.8 kb band was seen in AKR/J, LG/J and MRL/Mp-lpr/lpr. PCR amplification of genomic DNA showed a single Sm-D gene product of 360 bp, which indicated a lack of intervening sequences. The Sm-D protein is thus highly conserved in evolution, probably owing to its essential role in the physiology of the cell.
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PMID:The murine Sm-D autoantigen: multiple genes, genetic polymorphism, evolutionary conservation and lack of intervening sequences in the coding region. 138 35

1. Immunoblot analysis of rat sperm head proteins revealed the presence of polypeptides recognized by anti-Sm serum obtained from patients with systemic lupus erythematosus. 2. Two of these polypeptides have molecular weights of 26,000 and 15,000 and they were identified as small nuclear ribonucleoprotein components present in other rat tissues. 3. When the autoimmune serum was used in the immuno-gold procedure for electron microscopy, gold particles were found only on the sperm nucleus. 4. The results indicate that some polypeptides of the small nuclear ribonucleoprotein complex are components of the rat sperm chromatin.
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PMID:Small nuclear ribonucleoprotein polypeptides in rat sperm. 145 30

Cross reactivity of patient lupus autoantibodies to the small nuclear ribonucleoprotein particles of many different types of animals is well documented. The aim of our research was to determine if any level of cross reactivity existed between proteins of common dietary plants and anti-Sm autoantibodies of lupus patient's sera, as has been found for scleroderma patient sera (Agris et al., Exptl. Cell Res. 189, 276-279, 1990). Protein extracts from soy bean, corn, spinach, and carrot were analyzed. At least one protein (molecular weight approximately 28,000 daltons) common to all the above protein extracts was recognized by most of the anti-Sm sera tested. Affinity purified antibody eluted from the 28 kilodalton plant protein specifically recognized the Sm proteins of a HeLa cell protein extract. Recognition of the 28 kilodalton dietary plant protein was found to be unique to anti-Sm lupus sera.
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PMID:Anti-Sm autoantibodies of systemic lupus erythematosus cross react with dietary plant proteins. 158 56

Antibodies to uridylic acid rich small nuclear ribonucleoprotein particles (UsnRNP) are mainly detected in patients with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MCTD). Particularly those directed against epitopes of the 70K protein of U1snRNP serve as important markers for the diagnosis of MCTD. To establish an ELISA for determination of anti-70K protein antibodies in patients' sera a 1239 bp long cDNA insert coding for the epitopes of the 70K protein was ligated into a fusion expression vector. The bacterially expressed fusion protein was purified by chromatography on DEAE cellulose. Microtiter plates were coated with the fusion protein as well as with partially purified calf thymus extract (CTE) containing all natural UsnRNP antigens and RNase digested calf thymus extract (CTERNase) in which the natural 70K antigen was destroyed by the nuclease treatment. 10,888 sera of patients with suspected or overt rheumatic disease were analyzed for antibodies against these antigens simultaneously. Antibodies against CTE or CTERNase were not detected in 9123 sera, none of these showed reactivity with the 70K protein indicating a high degree of specificity of the assay. Positive results in each the 70K protein, CTE as well as the CTERNase ELISAs were obtained with 474 sera. 319 sera were only positive with CTE and 70K protein. Of these 793 anti-70K protein ELISA positive sera, 79% could be confirmed by immunoblot. Of 967 sera reacting with CTE and CTERNase but not with the recombinant 70K protein, 31% contained antibodies against various other UsnRNP proteins as shown by immunoblotting. 2.4% of these sera revealed also antibodies against the 70K protein. The use of the recombinant 70K protein as antigen meets the criterion for a simple and specific assay to detect anti-U1snRNP antibodies. Nevertheless, the sole use of this recombinant protein for anti-U1snRNP antibody screening may not be appropriate, because antibodies against other frequently occurring U1snRNP proteins (A, C) cannot be detected with this test. Therefore it should be used together with a natural UsnRNP antigen until further studies in patients with well established diagnoses will show whether natural antigens may be omitted.
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PMID:A recombinant 70K protein ELISA. Screening for antibodies against U1snRNP proteins in human sera. 183 68

The nucleoplasmic U small nuclear ribonucleoprotein particles (snRNP) have a set of seven proteins in common which are designated B', B, D, D', E, F and G. Patients suffering from rheumatoid autoimmune diseases such as systemic lupus erythematosus often develop autoantibodies against the proteins B', B, and D. Here we describe a sensitive immunoassay which allows the specific detection of autoantibodies reacting with the E, F or G snRNP proteins. We were able to identify several patient sera containing autoantibodies against one or more of these proteins. This demonstrates that all snRNP proteins described so far are potentially antigenic in systemic rheumatoid diseases. The characterization of the antibodies showed an immunological cross-reactivity between the snRNP protein G and the 70-kDa protein of U1 snRNP. Several sera contained autoantibodies which were specific for the F snRNP protein.
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PMID:Autoantibody production against the U small nuclear ribonucleoprotein particle proteins E, F and G in patients with connective tissue diseases. 213 85

An autoantibody from a patient with lupus-overlap syndrome was found to bind a specific region of U1 RNA. By using RNA sequence analysis, immunoprecipitation, and competition experiments with in vitro synthesized fragments of U1 RNA, a region of 40 nucleotides representing a stem-loop secondary structure was found to be an immunoreactive domain. This antibody recognized a conformational epitope because neither the RNA stem nor the RNA loop alone was immunoprecipitable. Antisense U1 RNA, U1 DNA, and other small RNAs were not reactive with the antibody. While the origins of nucleic acid-binding antibodies are unknown, this RNA-specific autoantibody probably originated by direct presentation to the immune system or as an anti-idiotype against a more common U1 small nuclear ribonucleoprotein-specific autoantibody. Thus, these findings have implications for the mechanisms of autoimmune recognition and provide an immunological approach to probing RNA structure and protein-RNA interactions.
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PMID:A sequence-specific conformational epitope on U1 RNA is recognized by a unique autoantibody. 245 54


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