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)

1. We describe new autoantibodies which recognize two cytoplasmic proteins of 30 and 26 kDa. They were detected by Western blot analysis in the sera of 6 of 79 randomly selected systemic lupus erythematosus (SLE) patients and are denoted anti-JA antibodies. This antibody specificity is different from the previously described lupus autoantibodies, anti-P and anti-S10. 2. The targeted autoantigens are trypsin sensitive, and resistant to RNase and DNase treatment. The binding to the antigens was not modified when reticulocyte ribosomes were prepared with protease inhibitors indicating that these are primary antigens and not degradation products. Several lines of evidence suggest that these proteins are almost certainly part of the ribosome. 3. Anti-JA reactivity was not observed in the sera from 60 patients with other autoimmune diseases or from normal individuals. In contrast, 55% of lupus sera selected for a high titer of anti-dsDNA (double stranded DNA) and LE cells were also anti-JA positive. 4. Anti-JA antibodies may be useful as a specific serological marker for disease activity in SLE. The strong association with anti-dsDNA antibodies and LE cell in the sera of SLE patients requires further study.
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PMID:Antibodies to new cytoplasmic autoantigens: anti-JA, a potential marker for disease activity in systemic lupus erythematosus. 134 36

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 because 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 serologic 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 these findings, 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 to break tolerance or that other abnormalities of the immune system are necessary for autoantibody production.
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PMID:Antiribosomal antibodies in systemic lupus erythematosus. 137 26

Antibodies to ribosomal protein components were examined in sera from 89 patients with active systemic lupus erythematosus (SLE). The anti-P, anti-S10 and anti-L12 antibodies were detected in 37, 28 and 2 patients, respectively. They were not detected in patients with various autoimmune diseases other than SLE or in healthy donors, which indicates that antiribosomal protein antibodies in sera are specific for patients with SLE. These antibodies are prevalent in patients with SLE and should provide good markers for the diagnosis of this disease.
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PMID:Autoantibodies against ribosomal proteins found with high frequency in patients with systemic lupus erythematosus with active disease. 178 88

Autoantibodies directed against a ribosomal small subunit protein of 20,000 molecular weight were found in sera from 5 of 44 patients with systemic lupus erythematosus (11%) and 5 of 48 MRL/lpr mice (10%). This ribosomal protein was identified as S10 on the basis of two-dimensional gel electrophoresis and immunoblotting, as well as immunoblots of the purified S10 protein. The S10 protein antigen was readily extracted from ribosomes at low salt (300 mM KCl) and low magnesium (0.5 mM) concentrations, consistent with the highly exposed location proposed for this protein on the 40S subunit. Anti-S10 antibodies were observed significantly more frequently in lupus sera containing both anti-Sm and antiribosomal P protein antibodies and in MRL/lpr sera with anti-Sm activity, suggesting a linked pattern of autoantibody response. Together with anti-Sm and antiribosomal P protein antibodies, anti-S10 represents a third autoantibody highly specific for lupus in humans and MLR/lpr mice.
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PMID:Antiribosomal S10 antibodies in humans and MRL/lpr mice with systemic lupus erythematosus. 247 35

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

A 24-year-old woman consulted a physician because of fever, dry cough, and arthralgia of one month duration. She was transferred to our hospital for more detailed examination of pancytopenia and diffuse infiltrative shadows on a chest X-ray film. On admission she was depressed, and had oral ulcers. Pleural and pericardial effusions were observed. Laboratory studies were positive for anti-nuclear antibody, anti-DNA antibody, and lupus erethymatosus. Casts were found in the urine, and systemic lypus erythematosus was diagnosed. Chest radiography and CT scan showed nodular shadows in the right S8 (2nodules with 1 cm diameter)(1 cm x 2), right S10 (0.5 cm diameter), and left S8 (0.5 cm diameter) regions, as well as diffuse infiltrative shadows in both lower lung fields. A specimen obtained by transbronchial lung biopsy revealed acute interstitial pneumonia with arteritis. After treatment with prednisolone (60 mg/day), the nodular and infiltrative shadows rapidly disappeared. Cases of lupus pneumonitis presenting as nodular shadows are very rare and are valuable in diagnostic imaging.
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PMID:[Acute lupus pneumonitis presenting as multiple nodular shadows]. 871 6

This study was carried out to clarify the frequency of detection of antibody activity to ribosomal protein S10 (anti-S10) in patients with systemic lupus erythematosus (SLE) with anti-Sm antibodies (anti-Sm), and clinical differences between anti-Sm-positive SLE patients with and without anti-S10. Twenty-seven of 31 serum samples containing anti-Sm reacted with ribosomal protein S10 along with Sm core proteins B/B' and D (87.1%). Four serum samples containing anti-Sm against only B/B' but not D did not react with S10 (12.9%). Patients who had both anti-Sm and anti-S10 showed lower serum complements levels, high frequency of skin lesion and anti-double-stranded DNA antibody. Many anti-Sm antibodies may recognize B/B', D, and S10 simultaneously, and such antibodies may appear in active disease.
Lupus 1999
PMID:High frequency of antibody activity against ribosomal protein S10 in anti-Sm sera from patients with systemic lupus erythematosus. 1048 11

Autoantibodies to the 20-kDa ribosomal proteins (L12/S10) are not well studied, especially in juveniles with systemic lupus erythematosus (SLE). Randomly selected sera from American juveniles and adults with SLE were screened for antibodies to either 20-kDa protein and P proteins and then assayed for anti-L12 and anti-S10 by immunoblot assays. In a pilot study of patients with anti-P (Cohort 1), IgG antibodies to either 20-kDa protein and, specifically, to L12 were observed in 72 and 42% of juveniles and adults, respectively. IgG antibodies to S10 were detected less frequently. In Cohort 2 patients who were chosen irrespective of autoantibody status, twice as many juveniles as adults had IgG antibodies to either 20-kDa protein. Prevalences of IgG anti-L12 and IgG anti-S10 antibodies in the juveniles were 28 and 16% and in the adults were 13 and 12%, respectively. Anti-L12 were strongly but not invariably associated with anti-P, and usually arose temporally to these antibodies. Anti-S10 activity was due to anti-Sm antibodies. We conclude that IgG anti-L12 are more prevalent in SLE than previously reported, and are responsible for the majority of activity toward the 20-kDa ribosomal proteins, especially in juveniles.
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PMID:Autoantibodies to the 20-kDa ribosomal proteins: identification, characterization, and new aspects on prevalence in systemic Lupus erythematosus. 1116 82

In view of the documented association of solute carrier family 19 member 1 (SLC19A1) G80A (R27H) polymorphism with the risk for different types of cancers and systemic lupus erythematosus (SLE), we have reanalysed the case-control study on breast cancer to ascertain the conditions in which this polymorphic variant exerts the risk of breast cancer. Association statistics have revealed that this polymorphism exerts the risk for breast cancer under the conditions of low folate intake, and in the absence of well-documented protective polymorphism in cytosolic serine hydroxymethyltransferase. To substantiate this observation, we have developed a homology model of SLC19A1 using glycerol-3-phosphate transporter (d1pw4a) as a template where 73% of the residues were modelled at 90% confidence while 162 residues were modelled ab initio. The wild and mutant proteins shared same topology in S3, S5, S6, S7, S11 and S12 transmembrane domains. The topology varied at S1 (28-43 residue vs 28-44 residue), S2 (66-87 residue vs 69-87 residue), S4 (117-140 residue vs 117-139 residue), S8 (305-325 residue vs 305-324 residue), S9 (336-356 residue vs 336-355residue), and S10 (361-386 residue vs 361-385 residue) transmembrane domains between wild versus mutant proteins. S2 domain is shortened by three amino acid residues in the mutant while in other domains the difference corresponds to one amino acid residue. The 3DLigandSite analysis revealed that the metallic-ligand-binding sites at 273Trp, 277Asn, 379Leu, 439Phe and 442Leu are although unaffected, there is a loss of active sites corresponding to nonmetallic ligand binding. Tetrahydrofolate and methotrexate have lesser affinity towards the mutant protein than the wild protein. To conclude, the R27H polymorphism affects the secondary and tertiary structures of SLC19A1 with the significant loss in ligand-binding sites.
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PMID:In silico analysis of the structural and functional implications of SLC19A1 R27H polymorphism. 3154 89