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)

Epidermal in-vivo nuclear reactions of IgG occur primarily in patients with mixed connective tissue disease or systemic lupus erythematosus and have been associated with high titres of circulating antibodies to ribonucleoprotein (RNP). This study was carried out to examine whether these epidermal nuclear reactions are true or simply an excision artefact. We observed the epidermal nuclear reactions for IgG only and not for other immunoglobulins in both in-vivo and in-vitro organ-culture studies, despite the presence of antinuclear antibodies (ANA) of all immunoglobulin classes. The association of the in-vitro epidermal nuclear reactions with serum RNP antibodies, although not absolute was statistically significant. The absorption of the serum with extractable nuclear antigen (ENA) preparation diminished the nuclear reactivity on tissue explants. In addition, the penetration of ANA into the nuclei of skin explants was both time and temperature dependent and was inhibited by sodium azide and by oligomycin. We conclude that the epidermal nuclear staining reactions observed by direct immunofluorescence on skin biopsies is selective and that the penetration of IgG into the epidermal cell nuclei is an active process and not an artefact.
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PMID:In-vivo epidermal nuclear reactions: a selective process. 187 2

Many laboratories have established ELISAs for the the routine detection of anti-cardiolipin antibodies (ACA). Earlier studies had indicated that assay incubation at 37 degrees C may interfere with the antigen binding capacity of these antibodies. We have reexamined this phenomenon by comparing ACA titers obtained when incubations are performed at either 37 degrees C or at room temperature (RT). In addition, the effect of coating antigen in aqueous or organic solution was compared. The sera tested included a set of recognized ACA standards and samples from 19 patients with SLE, two with primary anti-phospholipid syndrome, 71 patients with a variety of autoimmune and non-autoimmune disorders and 210 blood bank controls. The results show that while some sera do perform better under either incubation temperature there was no correlation between ACA titers and incubation temperature on a population basis either for IgG or IgM isotypes. This was seen both for positive standards and patient sera. For IgG ACA a similar phenomenon was seen if the microplates were coated with cardiolipin either in sodium carbonate or ethanol. For IgM ACA there was a significant increase in ACA titers at RT when cardiolipin was coated in ethanol. The data suggest that for most sera neither the antigen coating medium nor the assay incubation temperature are important variables in the determination of IgG ACA. Factors contributing to the influence of either variable in individual sera could not be identified.
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PMID:The effects of incubation temperature and coating procedure on the measurement of antibodies to cardiolipin. 191 34

The addition of urea to sodium dodecyl sulfate (SDS)-polyacrylamide gels has allowed the identification and characterization of the small nuclear ribonucleoprotein particle (snRNP) D' protein and has also improved resolution of the E, F, and G snRNP core proteins. In standard SDS-polyacrylamide gels, the D' and D snRNP core proteins comigrate at approximately 16 kilodaltons. The addition of urea to the separating gel caused the D' protein to shift to a slower electrophoretic mobility that is distinct from that of the D protein. The shift to a slower electrophoretic mobility in the presence of urea suggests that the D' protein has extensive secondary structure that is not totally disrupted by SDS alone. Both N-terminal sequencing and partial peptide maps indicate that the D and D' proteins are distinct gene products, and the sequence data have identified the faster moving of the two proteins as the previously cloned D protein (L. A. Rokeach, J. A. Haselby, and S. O. Hoch, Proc. Natl. Acad. Sci. USA 85:4832-4836, 1988). In the cytoplasm, the D protein is found primarily in the small-nuclear-RNA-free 6S protein complexes, while the D' protein is found primarily in the 20S protein complexes. Like the D protein, the D' protein is an autoantigen in patients with systemic lupus erythematosus and is recognized by some of the Sm class of autoimmune antisera.
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PMID:Identification and characterization of the small nuclear ribonucleoprotein particle D' core protein. 214 5

Quinidine, procainamide and disopyramide are antiarrhythmic drugs in the class 1A category. These drugs have a low toxic to therapeutic ratio, and their use is associated with a number of serious adverse effects during long term therapy and life-threatening sequelae following acute overdose. Class 1A agents inhibit the fast inward sodium current and decrease the maximum rate of rise and amplitude of the cardiac action potential. Prolonged Q-T interval and, to a lesser extent, QRS duration may be observed at therapeutic concentrations of quinidine. With increasing plasma concentrations, progressive depression of automaticity and conduction velocity occur. 'Quinidine syncope' (a transient loss of consciousness due to paroxysmal ventricular tachycardia, frequently of the torsade de pointes type) occurs with therapeutic dosing, often in the first few days of therapy. Extracardiac adverse effects of quinidine include potentially intolerable gastrointestinal effects and hypersensitivity reactions such as fever, rash, blood dyscrasias and hepatitis. Procainamide produces electrophysiological changes that are similar to those of quinidine, although Q-T interval prolongation with the former is less pronounced at therapeutic concentrations. Hypersensitivity reactions including fever, rash and (more seriously) agranulocytosis are associated with procainamide, and a frequent adverse effect requiring cessation of therapy is the development of systemic lupus erythematosus. Of the 3 drugs, disopyramide has the most pronounced negative inotropic effects, which are especially significant in patients with pre-existing left ventricular dysfunction. As with quinidine, unexpected 'disopyramide syncope' at therapeutic concentrations has been described. Anticholinergic side effects are common with this drug and may require cessation of therapy. Disopyramide therapy may unpredictably induce severe hypoglycaemia. Severe intoxication with the class 1A agents may result from acute accidental or intentional overdose, or from accumulation of the drugs during long term therapy. Acute overdose can result in severe disturbances of cardiac conduction and hypotension, frequently accompanied by central nervous system toxicity. Decreased renal function can cause significant accumulation of procainamide and its active metabolite acecainide (N-acetyl-procainamide), resulting in severe intoxication. Mild to moderate renal dysfunction is less likely to lead to quinidine or disopyramide intoxication, unless renal failure is severe or concurrent hepatic dysfunction is present. Management of acute intoxication with class 1A drugs includes gut decontamination with provision of respiratory support and treatment of seizures as needed. Hypertonic sodium bicarbonate, by antagonising the inhibitory effect of quinidine on sodium conductance, may reverse many or all manifestations of cardiovascular toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Poisoning due to class IA antiarrhythmic drugs. Quinidine, procainamide and disopyramide. 228 95

The putative cross-reaction of anti-DNA antibodies with "lupus-associated membrane proteins (LAMP)" on the surface of intact Raji cells was examined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analyses. Cell surface proteins of 14, 17, 18, 33 and 34 kDa were detected by monoclonal anti-double-stranded (ds) DNA antibodies and the sera of patients with systemic lupus erythematosus (SLE) in active states, but were not detected by the sera of SLE patients in inactive states, nor in healthy controls. However, pre-treatment of these anti-DNA antibodies with DNase I markedly reduced the reactivity to the cell surface proteins. Judging from the electrophoretic mobility, these proteins were identical with histones, and purified histones inhibited the reaction of anti-DNA antibodies with the cell surface proteins. Moreover, affinity-purified antihistone antibodies could demonstrate histones in the Raji cell surface proteins. Thus, we conclude that "cross-reaction" of anti-DNA antibodies with LAMP is due to DNA-anti-DNA immune complexes which could react with cell surface histones.
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PMID:Interpretation of the cross-reactivity of anti-DNA antibodies with cell surface proteins: the role of cell surface histones. 230 91

All nine SLE (systemic lupus erythematosus) sera with antiribosomal antibody activity targeted the same three ribosomal protein antigens, of molecular masses 38 and 17/19 kD when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. One serum reacted with an additional protein of approximately kD. Ribosomal subunit fractionation by composite gel electrophoresis and sucrose density ultracentrifugation showed that these proteins were part of the large subunit. Isoelectric focusing in agarose, and two-dimensional polyacrylamide gel electrophoresis revealed that the antigens had pI between 4.5 and 6.5, but that the 17/19 kD antigens were more acidic than the 38 kD antigen. Similarities in the molecular masses, charges, as well as the presence of highly conserved crossreactive epitopes, failure to bind to carboxymethylcellulose at pH 4.2, and extractability of the 17/19 kD proteins by 400 mM NH4Cl-ethanol at 0 degrees C indicated that these antigens were analogous to the proteins P0 (38 kD) and P1/P2 (17/19 kD) described previously (25, 36). Co-identity was confirmed using reference antibodies and antigen. Although antibodies to these proteins were only found in 5-10% of more than 50 sera screened by radioimmunoassay or Western blotting, the selective production of antibodies to epitopes on three (out of a total of more than 80) ribosomal proteins may provide further clues to autoantibody induction of SLE.
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PMID:Lupus autoantibodies target ribosomal P proteins. 241 May 26

A DP serological allospecificity was identified using 125I-labeled preparations of HLA class II molecules isolated from cells of HLA homozygous typing cell lines, SLE (DRw6, DQw1, DPw3) and WT46 (DRw6, DQw1, DPw2), and depleted of DR molecules by absorption with an anti-DR monoclonal antibody. The specificity, provisionally called WT, was carried by class II molecules possessing the characteristics of DP molecules on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and detected primarily in DPw1, DPw3 and DPw5 cells and exceptionally in some DPw2 cells including WT46 and DPw4 cells on a large panel of DP-pretyped B cell lines mostly derived from the 10th International Histocompatibility Workshop B cell reference panel. It was apparently allelic to another DP serological specificity BUT previously defined on DP molecules isolated from cells of DPw2+ HLA deletion mutant cell line LCL 721.82. On the same cell panel; the BUT specificity was negative in all DPw1, DPw3 and DPw5 cells, and positive in all DPw2 and DPw4 cells and also in DPw2B and DPw4B cells except the cells typed WT+. This DP association pattern was similar to that of the known allelic sequences, GGPM and DEAV, in DP beta F segment, one of the six variable segments in the second exon of DP beta gene. Thus, genomic DNA from 22 B cell lines pretyped for BUT and WT specificities were enzymatically amplified for the second exon of DP beta gene by the use of locus-specific oligonucleotide primers and hybridized with 32P-labeled oligonucleotide probes corresponding to the F segment sequence variations. This oligonucleotide typing showed perfect one-to-one correlation with the BUT and WT serological typing. The typing also revealed that WT46 cells, although typed DPw2, have the DEAV sequence common to DPw1, DPw3 and DPw5.
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PMID:Serological detection and molecular localization of allelic HLA-DP supertypic epitopes. 246 2

Binding of C3 to sheep erythrocytes in a serum-free milieu (EAC14oxy2, EAC142) has previously been shown to mimic the antigenic change that occurs upon denaturation of C3 in sodium dodecyl sulphate (SDS), whereby neoantigenic C3(D) epitopes are exposed. The present paper deals with C3 bound to various target surfaces which are known to modulate the functional properties of C3 in different ways. Bound C3 fragments on serum-treated human aggregated gammaglobulin, zymosan, rabbit and sheep erythrocytes, and on circulating immune complexes isolated from sera of patients with rheumatoid arthritis and systemic lupus erythematosus, were shown to be mainly in the iC3b form. By RIAs, employing polyclonal antibodies, the range of C3(D) antigenic epitopes of 125I-labelled SDS denatured C3 expressed by the particle-bound iC3b was monitored. The physiologically bound iC3b on all tested particles expressed wide range of C3(D) epitopes and each type of particle-bound C3 exposed its individual range. By competition ELISA specific C3(D) alpha epitopes were monitored, employing monoclonal antibodies. A distinct difference in the expression of these epitopes was observed in iC3b bound to various test particles in the presence of normal serum and in iC3b present on circulating immune complexes from pathological sera. Considering that the neoantigenic C3(D) epitopes have been shown to be associated with different functions of C3, the distinctive antigenic expression of each type of serum-treated particle might reflect different functional forms of the protein.
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PMID:Distinctive expression of neoantigenic C3(D) epitopes on bound C3 following activation and binding to different target surfaces in normal and pathological human sera. 246 49

Quantitative changes of concanavalin A (Con A)-reactive proteins in serum samples obtained from rats with induced inflammation and from patients with inflammatory and autoimmune diseases were examined by use of lectin blots. Treatment of rats with a single dose of fermented yeast to induce inflammation caused an extensive increase in Con A-reactivity. These changes were time dependent and were similar in both sexes of the animals. When we examined serum samples obtained from patients with various inflammatory disorders for their Con A-reactive proteins as compared with normal donors, we noted that the Con A-reactivity increased in patients with rheumatoid arthritis and systemic lupus erythematosus. Among all the glycoproteins examined by lectin blots with use of Con A, a set of five proteins was selected for detailed analysis by densitometric scanning. These included alpha 2-macroglobulin, P-150, P-95, P-40, and P-35, of Mr 180,000, 150,000, 95,000, 40,000, and 35,000, respectively, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Densitometric scanning analysis of the lectin blots revealed that the Con A-reactivity of these proteins increased during inflammation. Because alpha 2-macroglobulin is not an acute-phase protein in humans, an increase in Con A staining of this protein suggested that altered glycation is associated with autoimmune diseases. Thus, study of changes in Con A-reactive proteins in human sera may facilitate our understanding of the etiology and pathophysiology of autoimmune diseases.
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PMID:Changes in concanavalin A-reactive proteins in inflammatory disorders. 247 95

MRL/Mp-lpr/lpr (MRL/l) mice spontaneously develop autoimmune kidney disease which resembles human systemic lupus erythematosus (SLE). Employing this strain of mouse, we examined the effect of several immunosuppressants and a newly synthetized anti-nephritic agent, 4-chloro-3',6'-dimethyl-2,2'-iminodibenzoic acid (TO-115) on both the development of immunological abnormalities and the clinical symptoms of autoimmune kidney disease. This study aimed to determine how much the magnitude of autoantibody suppression related to the degree of prevention of autoimmune nephritis. Immunological abnormalities were assessed by measuring the serum levels of anti-deoxyribonucleic acid and anti-trinitrophenyl antibodies, rheumatoid factor (RF), and immune complex (IC). The status of autoimmune kidney disease was monitored by means of the appearance of proteinuria and survival time and the measurement of serum levels of blood urea nitrogen (BUN) and cholesterol. Immunosuppressants such as cyclophosphamide (CY), 6-mercaptopurine (6 MP) and sodium aurothiomalate (SAT) remarkably suppressed the development of immunological abnormalities in a dose dependent manner. Interestingly, however, only CY showed the suppressive effect on the development of autoimmune kidney disease with prolongation of survival time and the excretion of proteinuria. In contrast, 6-MP and SAT did not inhibit the development of autoimmune kidney disease. On the other hand, TO-115 did not suppress the development of immunological abnormalities, but it restrained the symptoms of autoimmune kidney disease. Taken together, the suppression of autoantibody production does not always lead to prevention of the development of autoimmune kidney disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of several kinds of drugs on the development of autoimmunity in MRL/Mp-lpr/lpr mice; lack of correlation between the suppression of autoantibody production and prevention of autoimmune disease. 252 11


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