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)

Chagas' disease, caused by the intracellular protozoan parasite Trypanosoma cruzi, is a major cause of heart failure in endemic areas. Antigenic mimicry by T. cruzi antigens sharing epitopes with host macromolecules has been implicated in the pathogenesis which is thought to have a significant autoimmune component. We report herein on the cloning and characterization of a full-length cDNA from a T. cruzi expression library encoding a protein, TcP0, that is homologous to the human 38-kD ribosomal phosphoprotein HuP0. The T. cruzi P0 protein shows a clustering of residues that are evolutionarily conserved in higher eukaryotes. This includes an alanine- and glycine-rich region adjacent to a highly charged COOH terminus. This "hallmark" domain is the basis of the crossreactivity of the highly immunogenic eukaryotic P protein family. We found that T. cruzi-infected individuals have antibodies reacting with host (self) P proteins, as well as with recombinant TcP0. Deletion of the six carboxy-terminal amino acids abolished the reactivity of the T. cruzi infection sera with TcP0. This is similar to the specificity of anti-P autoantibodies described for a subset of patients with systemic lupus erythematosus (SLE) (Elkon, K., E. Bonfa, R. Llovet, W. Danho, H. Weissbach, and N. Brot. 1988. Proc. Natl. Acad. Sci. USA. 85:5186). These results suggest that T. cruzi P proteins may contribute to the development of autoreactive antibodies in Chagas' disease, and that the underlying mechanisms of anti-P autoantibody may be similar in Chagas' and SLE patients. This study represents the first definitive report of the cloning of a full-length T. cruzi antigen that mimics a characterized host homologue in structure, function, and shared antigenicity.
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PMID:Cloning and expression of Trypanosoma cruzi ribosomal protein P0 and epitope analysis of anti-P0 autoantibodies in Chagas' disease patients. 137 23

A Trypanosoma cruzi cDNA lambda gt11 recombinant, C-P0, encoding the carboxyterminus of a highly antigenic ribosomal P protein, was isolated. Sequence comparisons and immunological evidence allowed its identification as the C-terminal region of the T. cruzi 38-kDa ribosomal P0 protein. This recombinant failed to react with systemic lupus erythematosus (SLE) anti-P antibodies. The T. cruzi ribosomal P0 protein is the first reported eukaryotic ribosomal P protein presenting this immunological property, probably due to its peculiar C-terminal-amino-acid sequence, FGMGALF, which differs from the conserved eukaryotic ribosomal P protein C-terminal consensus, MGFGLFD.
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PMID:Characterization of the C-terminal region of a Trypanosoma cruzi 38-kDa ribosomal P0 protein that does not react with lupus anti-P autoantibodies. 138 17

Ninety one Japanese patients with systemic lupus erythematosus (SLE) were studied to determine the clinical significance of antibodies to ribosomal P protein (anti-P). Anti-P was detected by western blotting in 38 of 91 patients (42%). Clinical symptoms of SLE were compared between patients with and without anti-P. The occurrence of lupus psychosis was significantly higher in patients with anti-P than in those without anti-P (9/38 v 1/53). No significant association was found between anti-P and other symptoms of SLE. These data strongly support the suggestion proposed by previous workers that anti-P is a marker autoantibody for the development of lupus psychosis.
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PMID:Correlation of antibodies to ribosomal P protein with psychosis in patients with systemic lupus erythematosus. 141 36

A Trypanosoma cruzi lambda gt11 cDNA clone, JL5, expressed a recombinant protein which was found to react predominantly with chronic Chagas' heart disease sera. The cloned 35-residue-long peptide was identified as the carboxyl-terminal portion of a T. cruzi ribosomal P protein. The JL5 13 carboxyl-terminal residues shared a high degree of homology with the systemic lupus erythematosus (SLE) ribosomal P protein epitope. Synthetic peptides comprising the 13 (R-13), 10 (R-10), and 7 (R-7) carboxyl-terminal residues of the JL5 protein were used to study, by enzyme-linked immunosorbent assay, the specificity of the Chagas' disease anti-JL5 and SLE anti-P antibodies. The R-13 peptide defined a linear antigenic determinant of the JL5 recombinant protein. As was proved for JL5, R-13 defined antibody specificities which were significantly increased in chronic Chagas' heart disease patients. Only SLE anti-P positive sera were found to react with JL5 and R-13. Fine epitope mapping showed that Chagas' disease anti-JL5 and SLE anti-P antibodies define similar epitopes within the R-13 peptide. The binding of the SLE sera to JL5 was completely blocked by the R-13 peptide, indicating that the shared specificity between anti-JL5 and anti-P autoantibodies was exclusively limited to the conserved linear epitope(s) within the R-13 peptide. The prevalence of high anti-R-13 antibody titers in Chagas' heart disease patients supports the hypothesis that postulates the existence of autoimmune disorders in Chagas' heart disease.
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PMID:Major Trypanosoma cruzi antigenic determinant in Chagas' heart disease shares homology with the systemic lupus erythematosus ribosomal P protein epitope. 169 82

The C terminal region of a Trypanosoma cruzi ribosomal P protein, encoded by the lambda gt11 JL5 recombinant, defined a major antigenic determinant in chronic Chagas heart disease. Immunopurified anti-JL5 antibodies were tested for anti-human ribosome reactivity by immunoblotting. They recognized the parasite ribosomal P proteins and clearly reacted with the corresponding human P proteins. The peptide R-13, that comprises the 13 C terminal residues of the JL5 recombinant and defines the specificity shared between chronic Chagas heart disease anti-JL5 antibodies and the systemic lupus erythematosus (SLE) anti-P antibodies, was used to study the specificity and the IgG subclass distribution of the anti-R-13 response by ELISA. The R-13 autoepitope is recognized mainly by sera from chagasic patients, but not by sera from malaria patients. Moreover, there was a significant correlation between anti-R-13 antibody levels and anti-T. cruzi antibody titres. The anti-R-13 response was mainly restricted to the IgG1 heavy chain isotype and correlated with the anti-T. cruzi isotype distribution.
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PMID:Humoral autoimmune response to ribosomal P proteins in chronic Chagas heart disease. 189 22

Three patients with systemic lupus erythematosus had positive antiribosomal P protein antibodies. The patients are women who had mild diseases that did not involve prominent internal organs. By using an immunofluorescence method for the detection fo antinuclear antibodies that employs HEp-2 cells, these serum samples produced intense stainings on cytoplasm and nucleoli that were digested with RNase. With the use of an immunoblotting technique, these serum samples recognized three ribosomal P proteins, called PO (38 kd), P1 (19 kd), and P2 (17 kd). We suggest that antiribosomal P protein antibodies can be detected in patients with systemic lupus erythematosus and associated mild clinical features.
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PMID:Systemic lupus erythematosus associated with antiribosomal P protein antibody. 220 7

Two models of murine graft-versus-host disease (GVHD) were studied with respect to autoantibody production and development of systemic lupus erythematosus (SLE) like disease. One model was induced by injection of (B10.A(4R) x B10.A(2R]F1 mice with parental (B10.A(4R] spleen and lymph node cells (groups I GVHD), the other by injection of (DBA/2 x C57/B16)F1 mice with DBA/2 cells (group II GVHD). Group I GVHD mice remained in a seemingly healthy condition and did not show any proteinuria, in spite of high titres of anti-nuclear antibodies including antibodies to dsDNA, anti-Sm and anti-ribosomal P protein antibodies. Measured levels of these autoantibodies as well as their isotypes were comparable with those found in MRL/lpr and NZB/W mice. Group II GVHD mice developed SLE-like disease signs, including severe proteinuria. At 4 months after induction of the GVHD, almost 50% of these mice had died. At the time nephritis was present, group II mice also produced anti-dsDNA and anti-nuclear antibodies of other (unknown) specificities, but no anti-Sm or anti-P. Furthermore, the incidence of these antibodies was lower than observed in group I GVHD, MRL/lpr or NZB/W mice. It is concluded that (high avidity) anti-dsDNA as well as anti-Sm and anti-P may be present in the circulation without giving rise to the development of nephritis.
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PMID:Fine specificities of anti-nuclear antibodies in murine models of graft-versus-host disease. 237 20

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

To identify Trypanosoma cruzi target antigens in overt Chagas' heart disease, a parasite lambda gt11 cDNA library was screened with the serum of a patient with a severe chagasic heart involvement (JL). Using a phage dot array immunoassay, 5 highly antigenic clones, JL1, JL5, JL7, JL8, and JL9, were probed with sera from clinically characterized T. cruzi infected subjects. The correlation of cloned T. cruzi antigen recognition with the clinical status of the subjects led to the identification of a recombinant antigen, JL5, that reacted predominantly with sera from patients with Chagas' heart disease. The antigenic determinant of the JL5 recombinant was a small 35 amino acid peptide. The nucleotide and the deduced amino acid sequence, together with other experimental data, allowed identification as the C-terminal portion of a T. cruzi P ribosomal protein. The C-terminal undecapeptide in JL5, EDDDMGFGLFD, was highly homologous to the same region of the human P protein SD(D/E)DMGFGLFD. The latter sequence has been identified as the P protein epitope in systemic lupus erythematosus (SLE). Positive SLE sera reacted with the JL5 recombinant phage, suggesting that the T. cruzi P protein might induce antibodies with a similar specificity to that of P antibodies in SLE.
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PMID:Identification of major Trypanosoma cruzi antigenic determinants in chronic Chagas' heart disease. 247 75

Anti-Sm and anti-ribosomal P protein antibodies show a high degree of specificity for the disease SLE. To determine whether a relationship between these two autoantibodies existed, the frequency of anti-P was determined in sera with and without anti-Sm activity. Of sera from lupus patients with anti-Sm 18/65 (28%), and 6/55 (11%) of sera without anti-Sm had anti-P as determined by an ELISA using a recombinant P2-beta-galactosidase fusion protein as Ag (p less than 0.05). The levels of anti-P were significantly higher in sera containing anti-Sm (0.37 +/- 0.45) than in sera without anti-Sm antibodies (0.18 +/- 0.20) (p less than 0.01). Similarly, a significantly higher proportion of anti-P positivity was found in autoimmune MRL/Mp-lpr/lpr mice positive for anti-Sm (11/53 = 21%) compared to age- and sex-matched mice without anti-Sm (3/53 = 6%) (p less than 0.05). The IgG subclass distributions for anti-Sm and anti-P antibodies were similar in the MRL mice (IgG2a greater than IgG2b greater than IgG3 greater than IgG1). The association did not reflect polyclonal B cell activation in a proportion of MRL mice because no significant differences were observed in anti-DNA, antichromatin or total serum IgG levels in mice with and without anti-Sm or, in mice positive for both anti-P and anti-Sm compared to mice positive for anti-Sm alone. Cross-inhibition experiments excluded the possibility that the Sm and P protein Ag shared a common epitope. Longitudinal measurement of anti-P and anti-Sm antibody levels by ELISA in three mice indicated that both antibodies first appeared at about 3 to 4 mo of age and fluctuated two- to threefold over 3 to 8 mo with independent peaks of activity. Recent observations regarding a relationship between anti-Sm and autoantibodies to other ribosomal proteins suggest that the association may be explained by an immune response to epitopes coassociated on the ribosome.
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PMID:Association between anti-Sm and anti-ribosomal P protein autoantibodies in human systemic lupus erythematosus and MRL/lpr mice. 276 Apr 62


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