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)

Phytohemagglutinin-induced cellular cytotoxicity by normal mononuclear cells (MNC) is inhibited by serum of patients with active untreated systemic lupus erythematosus (SLE) but not by that of patients with untreated inactive SLE or rheumatoid arthritis. Three-hour preincubation of normal MNC with SLE sera suffices to inhibit throughout the assay. Preincubation with phytohemagglutinin (PHA) before addition of sera does not prevent the inhibition. DEAE-cellulose chromatography, Sephadex G-200 fractionation and immunoelectrophoretic analysis have shown the nonimmunoglobulin nature of this factor. It is thermostable and not affected by deoxyribonuclease or ribonuclease treatment. The mitogen-induced cellular cytotoxicity-inhibiting factor seems to be independent of other serum factors capable of blocking PHA-induced blastogenic transformation.
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PMID:PHA-induced cellular cytotoxicity. Inhibition by a nonimmunoglobulin factor present in sera from patients with active systemic lupus erythematosus. 75 20

Sera from 29 patients with systemic lupus erythematosus (SLE), 60 cases of rheumatoid arthritis, 34 of myasthenia gravis (MG), 10 of scleroderma and 20 control sera were investigated for the occurrence of antibodies to native, double-stranded (ds) deoxyribonucleic acid (DNA). An immunofluorescence procedure recently elaborated by Aarden and coworkers, which utilizes the kinetoplast of the hemoflagellate Crithidia luciliae as substrate, was employed. In this kinetoplast, native, ds-DNA is concentrated as a single large network. Antibodies reacting with kinetoplasts were restricted to the SLE group, with the exception of one MG serum which also exhibited a distinct kinetoplast fluorescence. The antibody activity of the SLE sera could be completely inhibited by small amounts of DNA and abolished by deoxyribonuclease treatment of the substrate. These findings underline the specificity of the test system for anti-ds-DNA antibodies and the high disease-specificity of these antibodies for SLE. With respect to its ease and speed of performance this highly reliable and specific flagellate test surpasses other known tests for the detection of anti-ds-DNA antibodies.
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PMID:[Kinetoplast of the flagellate crithidia luciliae: a suitable substrate for the detection of antibodies to native, double-stranded DNA in the indirect immuno-fluorescence test (author's transl)]. 77 3

The clinical association of lupus anticoagulant antibodies with thrombocytopenia and thrombosis was the rationale for investigating the in vitro reactivity of these human hybridoma lupus anticoagulant antibodies with platelets. Fifty human hybridoma antibodies from 13 patients with systemic lupus erythematosus, 2 women with multiple spontaneous abortions, and 4 normal individuals were analyzed for lupus anticoagulant, antiplatelet, anti-DNA, and antiphospholipid reactivities. Of the hybridoma antibodies studied, 25 had lupus anticoagulant activity, 21 had antiplatelet reactivity, and 7 of these antibodies had both lupus anticoagulant and antiplatelet properties. No correlation was found between lupus anticoagulant antibody activity and antiplatelet, anti-denatured DNA, anticardiolipin, anti-egg phosphatidylethanolamine, antiphosphatidylserine, antiphosphatidylinositol, and antiphosphatidylcholine reactions. In contrast, antiplatelet activity was strongly correlated with antiphosphatidylethanolamine (rho = 0.761, p less than 0.001), anticardiolipin (rho = 0.748, p less than 0.001), and anti-dDNA (rho = 0.745, p less than 0.001) reactivities. Pretreatment of platelets with deoxyribonuclease, ribonuclease, trypsin, or phospholipases A2 and C resulted in different effects on the binding of individual hybridoma antibodies to platelets, suggesting that antiplatelet antibodies may recognize different epitopes on the platelet membrane. Our data demonstrate that most hybridoma lupus anticoagulant antibodies did not bind directly to platelets in vitro. This suggests that additional serum factors may be required in vivo to explain the association of these antibodies with thrombocytopenia and thrombosis.
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PMID:Lupus anticoagulant and antiplatelet properties of human hybridoma autoantibodies. 311 88

The gammaG-globulin eluted at acid pH from kidney cortex homogenates and isolated glomeruli of five of six patients with lupus nephritis was found to exhibit antinuclear activity, which was not dependent on presence of fresh human serum. Specificity, as demonstrated by absorption of antinuclear activity, was related to nucleoprotein in three glomerular acid eluates and to DNA in two acid eluates as well as in a deoxyribonuclease digest of disrupted glomeruli in one patient. Antinuclear activity was not found in acid eluates of kidneys from two patients with chronic liver disease and chronic discoid lupus, respectively, and one with lupus nephritis. These patients had a low titer of serum antinuclear factor and lesser amounts of kidney bound immunoglobulins. The presence of antinuclear activity in eluates of kidneys appeared to correlate with the amount of glomerular bound immunoglobulin and the level of antinuclear antibodies in serum. These findings suggest that in lupus nephritis, part of the glomerular bound immunoglobulin is derived from serum antinuclear factors possibly deposited as immune complexes.
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PMID:Immunopathologic studies of systemic lupus erythematosus. II. Antinuclear reaction of gamma-globulin eluted from homogenates and isolated glomeruli of kidneys from patients with lupus nephritis. 416 60

Antibodies were eluted from the isolated glomeruli prepared from the kidneys of 10 patients with the nephritis of systemic lupus erythematosus. Antibodies reacting primarily with buffer extracts of nuclei were eluted by acid treatment, and antibodies reacting mainly with DNA and nucleoprotein were eluted with deoxyribonuclease. Quantitative immunochemical studies revealed a high concentration of antinuclear antibody per milligram of gamma-globulin in glomerular eluates compared with that in the corresponding serums. The gamma-globulin of two eluates was found to consist predominantly of antinucleoprotein antibody. The selective elution of antinuclear antibodies was also indicated by the absence of other serum antibodies in the eluates. DNA antigen was demonstrated in the glomeruli of two kidneys with nephritis by means of isolated anti-DNA antibody labeled with fluorescein. In one of these cases, anti-DNA antibodies were also found concentrated in the glomeruli and, in the second, circulating anti-DNA antibodies were demonstrated in the patient's serum. The immunochemical evidence for the high specific activity of antinuclear antibodies and the association of DNA antigen with DNA antibody in glomeruli add further support for the antigen-antibody complex hypothesis for renal injury in systemic lupus erythematosus.
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PMID:Immunological studies concerning the nephritis of systemic lupus erythematosus. 416 98

Rabbits immunized with ultraviolet-irradiated DNA (UV-DNA) produced high titers of serum antibody. This experimental model was studied to determine if injection of antigen (UV-DNA) intravenously into immunized animals would induce glomerulonephritis and proteinuria. Proteinuria was observed several days after the start of daily intravenous injections into immunized animals and was sustained as long as injections were continued, but fell to normal values after stopping antigen administration. The kidneys showed glomerulitis sometimes associated with focal proliferative lesions, and immunofluorescence showed rabbit Ig and C3 in glomeruli. By electron microscopy, electron-dense subendothelial deposits were seen. Sucrose density gradient analyses of sera immediately after antigen injections suggested the presence of immune complexes of DNA and antibody since both heavy sedimenting and 7S Ig were detected. After digestion with deoxyribonuclease rabbit Ig could be found only in the 7S sedimenting fractions. Intravenous injection of UV-DNA into normal, nonimmune animals did not produce heavy sedimenting Ig or abnormal sedimentation patterns. These studies with an experimental model might provide insight into pathogenetic mechanisms operating in systemic lupus erythematosus where the importance of DNA-anti-DNA immune complexes have been documented. The studies suggested that gradual accumulation of DNA immune complexes in glomeruli might be one mechanism causing renal functional abnormalities.
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PMID:Experimental renal disease induced by DNA-anti-DNA immune complexes. 455 Apr 91

Several types of antipolynucleotide antibodies were eluted by acid buffer or deoxyribonuclease treatment of glomeruli obtained from nine kidneys from patients with systemic lupus erythematosus (SLE). Anti-SDNA antibodies were found concentrated over serum levels in eight eluates, anti-NDNA in six eluates and anti-RNA Pr in four eluates; anti-DSRNA antibodies were not demonstrable in any eluate tested. Deoxyribonuclease treatment eluted a high incidence and greater quantity of anti-NDNA and anti-SDNA antibody, whereas anti-RNA Pr antibody was mainly eluted by acid buffer. Simultaneous studies of antibody and antigen in serial serum specimens and in glomeruli suggested that complexes of SDNA antibody or antigen excess were frequently deposited in SLE kidneys, in addition to complexes containing anti-NDNA and anti-RNA Pr. It was observed that studies of antibody titers alone were inadequate for predicting the types of complexes deposited in the kidney. Either antigen excess could obscure detection of humoral antibody or extremely high titers of antibody as observed for RNA Pr are not conducive to the formation of kidney localizing immune complexes in the absence of antigen. Immunofluorescence studies demonstrated the presence of SDNA antigen in most cases from which anti-SDNA antibody was eluted providing direct evidence for the presence of SDNA-anti-SDNA complexes in renal glomeruli. A study of complement components indicated that Clq was absent from cases in which little or no SDNA was deposited in renal glomeruli; although all nephritic kidneys demonstrated C3 deposits. Several hypotheses accounting for this observation are discussed, including the probable utilization of the alternate pathway by certain types of complexes and a direct reaction between C1q and circulating or tissue-bound NDNA or SDNA.
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PMID:Polynucleotide immune complexes in serum and glomeruli of patients with systemic lupus erythematosus. 480 10

The indirect fluorescent-antibody (IFA) method for diagnosis of toxoplasmosis is widely used and is considered to be as specific as the Sabin-Feldman dye test. After observing a patient with systemic lupus erythematosus (SLE) who had a positive toxoplasma IFA test but a negative dye test, we studied sera with high titers of antinuclear antibodies from 16 SLE patients and from 2 with rheumatoid arthritis for Toxoplasma antibodies in the immunoglobulin G and M (IgG and IgM) IFA tests and the dye test. Results of these tests were compared with titers of antinuclear antibodies, precipitating antibodies to single-strand deoxyribonucleic acid (DNA), and binding antibodies by use of DNA labeled with (3)H-actinomycin D. Of 18 patients, 11 had IgG and 4 had IgM IFA Toxoplasma antibodies; only 2 had antibodies detectable in the dye test. The immunofluorescence patterns in the Toxoplasma IFA test were indistinguishable from those obtained in patients with toxoplasmosis without antinuclear antibodies. Absorption of SLE sera with DNA did not result in a decrease in Toxoplasma IFA titers. When SLE sera were absorbed with live T. gondii, a marked drop in IgG IFA titer was observed as well as a decrease in titers of antinuclear antibodies and (3)H-DNA binding. Treatment of Toxoplasma cells with deoxyribonuclease and ribonuclease did not decrease their fluorescence. These results suggest that T. gondii nuclear antigens can absorb antinuclear antibodies but do not have exposed substrates for deoxyribonuclease. Tests in which organisms containing "nuclear" antigens for IFA detection of antibodies to these organisms are used may result in "false-positives" with sera containing antinuclear antibodies.
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PMID:False-positive anti-Toxoplasma fluorescent-antibody tests in patients with antinuclear antibodies. 494 Aug 68

A nuclear antigen associated with cell proliferation (proliferating cell nuclear antigen [PCNA]) and blast transformation is recognized by autoantibodies in the sera of some patients with systemic lupus erythematosus. Using this autoantibody as a reagent, PCNA was purified 120-fold by ammonium sulfate fractionation, DEAE chromatography, and Sephadex G200 gel filtration. The antigenicity of PCNA was sensitive to trypsin but resistant to ribonuclease and deoxyribonuclease, suggesting that the antigenic determinant resided in protein and not nucleic acids. PCNA was inactivated at 56 degrees C for 30 min. Isoelectrophoretic focusing showed that the pI was 4.8. Analysis of immunoprecipitates on polyacrylamide gels showed the presence of IgG heavy and light chains and a single polypeptide band of 33,000 mol wt. This polypeptide band was the reactive antigen in immunoblotting (Western transfer) assays.
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PMID:Characterization of proliferating cell nuclear antigen recognized by autoantibodies in lupus sera. 614 19

Sera of patients with primary biliary cirrhosis (PBC) were examined for the presence of precipitating antibodies to sonicated rat liver mitochondrial (M) fraction. Three distinct precipitating systems observed in double immunodiffusion were identified and called M-A, M-B and M-C. Unsonicated mitochondria did not form precipitin lines. Precipitating system M-A was found in nineteen of twenty (95 percent) sera from PBC. The mitochondrial antigen of M-A system had the unusual property of being resistant to enzymatic digestion with deoxyribonuclease (DNase), ribonuclease (RNase) and trypsin under standard conditions. The titres of antibody to M-A antigen correlated (P less than 0.05) with titres of mitochondrial immunofluorescence staining on unfixed mouse kidney sections. Precipitating systems M-B and M-C were present in seven of twenty ribonuclease and trypsin but resistant to ribonuclease indicating that it could be DNA-protein complex. The M-C antigen was destroyed by trypsin suggesting its protein character, but it was difficult to determine if nucleic acids might also be associated with antigenicity. The antibodies to mitochondrial antigens were not present in normals (fifteen health adults), systemic lupus erythematosus (forty patients), rheumatoid arthritis (fifteen patients) and chronic liver diseases (fifteen patients). The antibodies did not show identity with antibodies to ribosomal ribonucleo-protein and other known nuclear antigens previously reported. The data confirm previous reports concerning the heterogeneity of mitochondrial antibodies present in sera of patients with PBC. The antibody to M-A antigen appeared to be a diagnostically useful immunological marker since it was present in the majority of patients with PBC.
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PMID:Preciitating antibodies to mitochondrial antigens in patients with primary biliary cirrhosis. 676 23


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