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)

Autoantibody to Sm Ag is a highly specific marker for the diagnosis of SLE. The Sm Ag exists in the cell nucleus as part of a ribonucleoprotein complex containing five small nuclear RNA. The major immunoreactive Sm species have been reported to be three polypeptides of m.w. 28,000/29,000 (B/B') and 16,000 (D). We report here that a m.w. 21,000 peptide is another major target of anti-Sm antibody. This peptide was originally identified by Western blotting as an acidic ribosomal protein (RP21) reactive with IgG from some SLE patients. Anti-RP21 is distinct from anti-ribosomal P protein antibody (anti-P) which has been previously identified as a lupus-specific autoantibody. Cell fractionation experiments showed that RP21 existed only in the ribosomal fraction and was never detected in other cellular compartments including nuclei. However, when nuclear extracts were used as Ag sources in immunoblotting, affinity-purified anti-RP21 was found to react with m.w. 28,000 and 16,000 peptides, suggesting that anti-RP21 reactivity might be due to the cross-reaction of anti-Sm. This was further confirmed by the evidence that two kinds of murine anti-Sm mAb independently derived from MRL/lpr mouse recognized RP21. These results indicate that anti-Sm antibodies in SLE are reactive with both nuclear and ribosomal ribonucleoproteins. Previous reports have described certain similarities, i.e., antibody subclass restriction and incidence, of anti-Sm and anti-P in both humans and autoimmune mice. Our present study demonstrated a close physical association of target molecules reactive with anti-Sm and anti-P, and might, therefore, provide some clue to the origin of these two types of lupus-specific autoantibodies.
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PMID:Identification of an acidic ribosomal protein reactive with anti-Sm autoantibody. 277 17

Autoantibodies may play an important role in the pathogenesis of central nervous system (CNS) disease in systemic lupus erythematosus (SLE). We obtained cerebrospinal fluid (CSF) and, in some cases, sera from 19 SLE patients with CNS lupus and from 12 SLE patients without CNS lupus. Autoantibodies to saline soluble cellular antigens were detected in the CSF of lupus patients and reflected those present in the serum. These antibodies were distinct from the previously described antineuronal antibodies. Analysis of the fine specificities of the anti-saline soluble cellular antigen antibodies revealed that the antiribosomal P protein antibody was present in 4 of 4 patients with lupus psychosis and was enriched in the CSF of 1 patient. Sera containing antiribosomal P protein showed prominent cytoplasmic staining of human cortical neurons, as well as an epithelial cell substrate. These observations, together with the increase in intrathecal IgG synthesis detected in 71% of patients tested, suggest that several populations of antibodies may contribute to the enhanced immunologic activity in the CSF of CNS lupus patients.
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PMID:Autoantibodies in the cerebrospinal fluid of patients with systemic lupus erythematosus. 375 38

This study investigated the prevalence and clinical significance of anti-ribosomal P protein (anti-P) antibodies in patients with systemic sclerosis (SSc). Serum samples from 150 patients with SSc were examined by indirect immunofluorescence. ELISA and immunoblotting. Anti-P antibodies were detected in four (3%) patients with SSc. Three of the four patients showed SSc/SLE (systemic lupus erythematosus) overlap syndrome, but psychiatric disorders were not observed in these patients. By longitudinal immunoblotting analysis one patient, who was initially diagnosed with SSc, later developed anti-P antibodies along clinical manifestations of SLE. Our data suggest that anti-P antibodies are uncommon in SSc and that the presence of anti-P antibodies in patients with SSc indicates an overlap with SLE.
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PMID:Detection of antiribosomal P protein antibodies in patients with systemic sclerosis. 758 93

Affinity-purified human polyclonal anti-double-stranded DNA antibodies (anti-dsDNA) exerted a cytostatic effect towards human and rat glomerular mesangial cells (MC). In order to identify the cognate antigens for anti-dsDNA on the surface of MC, we used these autoantibodies to probe a human renal lambda gt11 cDNA expression library. Two cDNA clones encoding the cognate proteins for the autoantibodies were isolated. Sequencing analysis of the two cDNA showed that they had 98.6% homology with the gene of the P0 and 99.2% homology with the gene of the P1 human acidic ribosomal phosphoproteins (P protein). Two galactosidase fusion proteins (125,000 and 150,000 MW) derived from the two cDNA inserts expressed in lysogenic Escherichia coli Y1089 could react with the original screening antibodies in an immunoblotting analysis. After transformation and expression of the full-length P1 clone in prokaryotic cells, the purified P1 protein was able to react with anti-dsDNA. In a cross-inhibition experiment, the dsDNA binding activity of anti-dsDNA was inhibited by a synthetic polypeptide corresponding to the carboxyl-terminal 20 amino acids of P protein and purified P1 protein in a dose-dependent manner, but this was less potent than the inhibition caused by calf thymus dsDNA. By use of well-defined systemic lupus erythematosus (SLE) sera, we found only sera containing a high titre of anti-dsDNA activity (> 300 IU/ml) reacted with P1 of rat MC lysate. Furthermore, the 38,000 and 19,000 MW macromolecules were proved to be the cognate antigens for anti-dsDNA expression on the surface of the MC, by Western blot of the MC plasma membrane lysates. These results suggest that anti-dsDNA may cross-react with ribosomal P proteins expressed on the surface of the MC and exert cytostasis towards these cells.
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PMID:Anti-dsDNA antibodies cross-react with ribosomal P proteins expressed on the surface of glomerular mesangial cells to exert a cytostatic effect. 764 15

We have cloned and characterized cDNA molecules that encode members of the acidic ribosomal protein family (TcP proteins) from the protozoan parasite Trypanosoma cruzi. These proteins have been shown to be antigenic in individuals with T. cruzi infection. Unlike other known eukaryotic cells, T. cruzi possesses at least four types of P protein genes TcP0, TcP1, TcP2a, and TcP2b, each of which is present in multiple copies in the genome. These genes are present on at least three different chromosomes. Although the abundance of TcP0, TcP2a, and TcP2b transcripts do not appear to vary among the parasite life-cycle stages, TcP1 is predominantly expressed in the epimastigote (insect) stage. TcP0 has a C-terminal heptapeptide sequence that is similar to those of archaebacterial acidic (P-like) proteins, but the TcP1/P2 proteins terminate with a shared sequence characteristic of the P proteins of higher eukaryotes. The serine residues or other potential phosphorylation sites typically found within the highly charged C-terminal acidic domain are absent in T. cruzi P proteins. Using synthetic peptides, we demonstrated that approximately 80% of T. cruzi-infected individuals produce two distinct but cross-reactive anti-P antibody specificities directed against the C-termini of TcP0 and TcP1/P2. We also expressed the full length (non-fusion) recombinant human P0 and demonstrated that the T. cruzi anti-P antibodies cross-react with the C-terminal residues of human P-proteins. Conversely, human anti-P protein antibodies in sera from patients with SLE cross-react with the C-terminal epitope of T. cruzi TcP1/P2 proteins. The cross-reactivity of anti-TcP antibodies with human P proteins suggests that, through antigenic conservation, TcP proteins may contribute to the development of autoreactive antibodies in Chagas' disease patients.
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PMID:Trypanosoma cruzi acidic ribosomal P protein gene family. Novel P proteins encoding unusual cross-reactive epitopes. 769 13

Autoantibodies directed against the ribosomal proteins P0, P1 and P2 (P proteins) are specific for systemic lupus erythematosus (SLE) and there are some evidences that they could be related to the neuropsychiatric manifestations of the disease. In this study, a multiple antigen peptide (MAP) carrying four copies of the C-terminal peptide (13 residues) of the P2 protein, which is a common epitope of the three P proteins, was prepared for use in an ELISA assay. It was employed to detect antibodies directed against the ribosomal P proteins in 102 SLE patients and the results were compared with those obtained using immunoblotting (IB). With this new ELISA, antiribosomal P protein antibodies were found in 15/102 SLE sera. These results correlated well with the results of IB. Furthermore, we confirmed that naturally occurring antiribosomal P protein antibodies are directed mainly against the epitope containing the C-terminal sequence and shared by the three P proteins. MAP appears to be an excellent coating agent for ELISA assays designed to detect anti-P antibodies. Further experiments showed the superiority of MAP, compared to the free peptide, in the detection of weakly positive sera. This ELISA can also be used for the serological follow-up of SLE patients.
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PMID:Autoantibodies directed against ribosomal P proteins: use of a multiple antigen peptide as the coating agent in ELISA. 787 67

ARA occur in approximately 10% of randomly selected SLE patients but in up to 40% of patients with active disease. Anti-P antibodies appear to be a highly specific diagnostic marker for SLE since they are rarely detected in other multisystem autoimmune disorders. ARA are most frequently directed against the P proteins and the shared conserved C-terminus of the P proteins is immunodominant in almost all sera tested. Anti-P antibodies increase in titer in patients with active disease and have been reported to be detected more frequently in patients with severe behavioral disturbances. This may be particularly true of patients with affective disorders. The clinical utility of serological tests for anti-P in central nervous system lupus must await large, prospective studies. Other ARA antibodies have been detected in patients with SLE. These antibodies include anti-28S rRNA, anti-S10, and anti-L12. In all cases, the frequency with which these antibodies are detected is increased in sera containing anti-P. The P proteins and the 28S rRNA epitope play essential, but as yet undefined, roles in GTPase activity on the ribosome. The L12 protein is the mammalian homologue of the E. coli and yeast proteins known to bind to the 28S rRNA epitope. These findings indicate that some SLE patients produce autoantibodies against multiple components of a functionally related domain of the ribosome. This, in turn, supports the notion that the ribosome initiates and/or maintains autoantibody production. Despite the evidence supporting an antigen driven immune response, attempts to induce anti-P antibodies by immunization with autologous ribosomes in the autoimmune strain of mouse, MRL, have been unsuccessful. It therefore seems likely that the ribosomal components must be altered in some way to break tolerance or that other abnormalities of the immune system are necessary for autoantibody production. Immunization with foreign ribosomes induce anti-P autoantibodies in mice and in apparently normal humans infected with the hemoflaggelate, T. cruzi. The ability of the P proteins to break tolerance in these situations is, most likely, explained by the provision of a T cell epitope (the foreign P protein) together with the multivalency of the P proteins on the ribosome (which activate autoreactive B cells). We therefore propose (Fig. 5) a two-signal model for autoantibody production similar to that suggested for T-B collaboration in the normal immune response and also in the GVHD model of lupus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antiribosomal antibodies in SLE, infection, and following deliberate immunization. 797 36

Antibodies to the ribosomal P protein are specific for SLE but their prevalence varies in different ethnic groups. In a group of Chinese SLE patients from Malaysia who have a high prevalence of this antibody, we have found an increased frequency of an uncharacterized HLA-DRB gene allele, DR16X, in patients who are positive for anti-P antibodies compared to antibody negative patients (31.3% vs 3.2%, P < 0.01, Pcorr not significant, relative risk = 13.6). DR16X has only been found in south east Asian populations and may be a genetic factor which influences the high prevalence of anti-P antibodies in Chinese.
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PMID:HLA-DRB genes and antiribosomal P antibodies in systemic lupus erythematosus. 800 Jul 39

The immunodominant epitope recognized by lupus antiribosomal P protein antibodies (anti-P antibodies) is located within the 11 C-terminal residues common to the three P proteins. This epitope contains a potential phosphorylation site for casein kinase II and clusters of acidic and hydrophobic amino acids. To determine the role of each of these features in antigen recognition, lupus anti-P sera were tested for binding to phospho- and dephospho- forms of the P proteins and to synthetic peptide antigens in which site-specific modifications had been introduced. Immunoblot analysis revealed that anti-P antibodies specific for the phospho- form of the P proteins represented only a minor population of anti-P antibodies and, in many cases, were absent altogether. In contrast, when charged substitutions were introduced into either the acidic or hydrophobic clusters and tested by ELISA, striking reductions of 64-86% were observed. Conservative Gly-->Pro substitutions also produced a 73% average reduction in anti-P binding whereas substitution of either Ser-105 or the C-terminal Asp-115 resulted in a < 35% reduction in binding. These findings suggest that phosphorylation of the P proteins does not play a role in antibody recognition but that anti-P antibodies require both the acidic and hydrophobic clusters for optimal binding to synthetic peptide antigens. The remarkable degree of specificity demonstrated by these antibodies supports the view that anti-P autoantibodies result from a highly specific (at the B cell level) immune response to self antigen.
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PMID:The effect of phosphorylation and site-specific mutations in the immunodominant epitope of the human ribosomal P proteins. 805 Feb 1

1. We have compared the sensitivity and specificity of immunofluorescence, counterimmunoelectrophoresis, immunodiffusion, Western blotting and ELISA for the detection of antiribosomal P protein antibodies using 153 lupus sera. 2. Western blotting and ELISA were the 2 most sensitive and specific techniques for the detection of these antibodies. In contrast, cytoplasmic immunofluorescence was observed in only one third of the anti-P-positive patients. Immunodiffusion and counterimmunoelectrophoresis, although highly specific, detecting 14% and 29% of all anti-P-positive sera by Western blotting, were the least sensitive tests. 3. The frequency of anti-P in lupus patients, as detected by Western blotting analysis was 18%. The most frequently observed antibody in anti-P sera was anti-Ro/SSA (39%). Anti-P antibodies were also detected in the sera of 3 patients with negative nuclear immunofluorescence. 4. Anti-P is an additional serological marker for systemic lupus erythematosus and Western blotting is the method of choice for detecting this antibody due to the limited availability of the fusion protein in Brazil.
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PMID:Comparison of five methods for the detection of antiribosomal P protein antibody. 808 Dec 88


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