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)

The nonobese diabetic (NOD) mouse, in which major histocompatibility complex genes may be involved in the susceptibility to diabetes, has been developed as a model of autoimmune diabetes. The NOD mouse expresses I-A-encoded class II major histocompatibility complex antigens, which differ from those of other mouse haplotypes by the presence of a serine at position 57 of the A beta chain. Identifying islet autoantigens may help elucidate the role of class II antigens in the activation of autoreactive T cells and, thus, in the development of diabetes. We have detected autoantibodies directed against a 58-kDa islet cell antigen in NOD mice but not in other strains, including lupus-prone mice. Apart from insulin-secreting cells, the 58-kDa antigen was only found to be expressed by neuroblastoma cells and was identified as peripherin, an intermediate filament protein previously characterized in well-defined neuronal populations. This autoantigen cross-reacted with I-Anod class II antigens, suggesting that it may contribute to defective self-tolerance of islet beta cells in the NOD mouse.
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PMID:Peripherin: an islet antigen that is cross-reactive with nonobese diabetic mouse class II gene products. 172 86

The antibody to cardiolipin(ACA) was tested in patients with systemic rheumatic disease. The frequency of IgG ACA was 46/100(46.0%) in systemic lupus erythematosus(SLE). In other rheumatic disease, this was less than 20%. Significant correlation between the presence of IgG ACA and thrombosis and/or thrombocytopenia was found in patients with SLE. Eight sera containing high titered IgG ACA from lupus patients were selected for further inhibition study. Inhibitors were consisted of cardiolipin(CL), phosphatidyl(p-)serine, p-inositol, p-glycerol, p-ethanolamine, p-choline, ds-DNA, ss-DNA, fresh platelets(PLT)and fresh red blood cells(RBC). All sera were markedly inhibited by negatively charged phospholipids. In 4 sera(group B), there was moderate inhibition by ss-DNA, ds-DNA, PLT and RBC. In another 4 sera(group A), mild but significant inhibition was obtained by PLT alone. The number of platelet in group A was less than that in group B. There were some differences in inhibitory activity, suggesting heterogeneity of antibody to CL. It may be possible to speculate that heterogeneity of IgG ACA cause various combination of clinical features such as thrombocytopenia and thrombosis.
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PMID:[Heterogeneity of anticardiolipin antibody]. 192 93

Ninety-seven psychiatric patients who have been treated with the antipsychotic drug chlorpromazine or another phenothiazine have been investigated for the presence of antiphospholipid antibodies. A variety of coagulation studies and specific antiphospholipid immunoassays were performed to define the spectrum of antigen specificity of these antibodies. Coagulation studies showed an increasing sensitivity for the lupus anticoagulant with reagents of differing phospholipid content. Prolonged activated partial thromboplastin times (APTTs) were found in five patients with the use of an insensitive APTT reagent and in 14 patients with a lower phospholipid content reagent. In every case, attempted correction of the clotting time with normal plasma was unsuccessful. Twenty-one patients had abnormal kaolin clotting time profiles. In seven of these patients, test results with both APTT reagents had been normal. Antibody reactivity was tested against three negatively charged phospholipids, phosphatidyl-serine, cardiolipin, and phosphatidylinositol. Only five patients demonstrated reactivity against phosphatidylinositol, whereas high antibody titers were observed in 28 patients against one or both of phosphatidylserine and cardiolipin. Twenty-three of these patients were found to have elevated anticardiolipin-specific IgM antibodies. Overall, 41 of the patients had at least one laboratory abnormality suggestive of antiphospholipid antibody activity. Seven of the 26 patients, taking phenothiazines other than chlorpromazine, had positive test results for antiphospholipid antibodies. No clinical thromboembolic events were recorded in any patient. These findings demonstrate the heterogeneity of antiphospholipid antibody specificity induced in patients treated with various phenothiazine drugs and indicate that none of these patterns of reactivity marks a predisposition for thromboembolism in this population.
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PMID:Heterogeneity of laboratory test results for antiphospholipid antibodies in patients treated with chlorpromazine and other phenothiazines. 197 39

Controversies exist as to the differences in the specificities of phospholipid antibodies in SLE and syphilis. We report an ELISA assay that could distinguish phospholipid antibodies associated with SLE and syphilis based on their differential reactions with phosphatidyl choline and VDRL antigens. Antibodies to phospholipid from patients with SLE reacted equally well when tested with these two antigens in the ELISA assay whereas phospholipid antibodies present in syphilis patients exhibited little or no binding to phosphatidyl choline. There were no differences in the binding of phospholipid antibodies to other phospholipids such as cardiolipin and phosphatidyl serine. In addition, there was no association of anti-phospholipid antibodies with the presence of either DNA or RPR antibodies suggesting their distinctness from each other.
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PMID:Anti-phospholipid antibody profiles of different specificities in syphilis and systemic lupus erythematosus. 207 16

Circulating lupus-type anticoagulant is associated with an increased risk of arterial or venous thrombosis. The laboratory identification of lupus coagulant requires at least 2 different in vitro phospholipid-dependent coagulation techniques: immunological assessment based upon Elisa-type tests using pure phospholipids complements the coagulation procedure, but does not replace it. Circulating lupus anticoagulant is correlated with anti-phospholipid antibodies specific to phosphatidyl serine. Relationships between circulating lupus anticoagulant and anti-cardiolipin seem complex and are discussed. In fact, an entire family of anti-phospholipid antibodies exists, whose relationship with clinical manifestations remains to be determined. The effects of anti-phospholipid antibodies on human endothelial cells are described.
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PMID:[Antiphospholipid antibodies: specificity and mechanism of action]. 211 12

The correlation between lupus anticoagulant (LA) potency and anticardiolipin antibody (ACA) ELISA was found to be poor (r = 0.40) in a group of 56 patients accumulated by a haematology department mainly for studies of LA. This correlation was similar whether LAs were assessed by kaolin clotting time or activated partial thromboplastin time increments. When the more procoagulant phospholipid phosphatidyl serine, used in a calcium-containing buffer, was substituted for cardiolipin in the ELISA, the correlation with LA was only slightly improved (r = 0.58). In fact, binding of antibody from patient plasmas to blank wells, although quantitatively reduced, was found to correlate equally well with LA activity. LAs are not necessarily phospholipid-binding antibodies but may interfere more generally with other surface-dependent processes in the clotting mechanism.
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PMID:Studies on the relationship between 'antiphospholipid' antibodies and the lupus anticoagulant. 212 89

To distinguish the properties of anti-DNA antibodies in patients with lupus from those in normal individuals, we compared the ligand binding, idiotypic and charge properties of serum anti-DNA antibodies derived from: patients with active lupus; normal individuals; and among Ig eluted from the kidneys of two patients with active lupus nephritis (one with mesangial proliferation and the other with membranous nephropathy). The kidney eluate anti-DNA antibodies were the most cross-reactive; they cross-reacted with ssDNA, poly(GdC), poly(dT), poly(dG), poly(dC), ZDNA, SmRNP and the phospholipids cardiolipin and phosphatidyl serine. Lupus serum anti-DNA antibody cross-reacted with polynucleotides but not with phospholipids, whereas anti-DNA antibodies derived from normal serum reacted only with poly(dT). An anti-idiotype (anti-IdD; produced against serum anti-DNA antibodies from one patient) reacted with: anti-DNA antibodies in 8/9 lupus sera; antibodies in both kidney eluates; and anti-DNA antibodies from 5/7 normal sera. Anti-IdD did not react with Ig that did not bind to DNA. Isoelectric focusing of Ig showed that the charge of anti-DNA antibodies from lupus serum and normal serum were similar and unrestricted (pI 5.4-9.0); Ig in kidney eluates varied: membranous lupus pI 4.5-8.6; mesangial lupus pI 8.1-9.1. We conclude that idiotypically related anti-DNA antibodies in tissue lesions, lupus serum and normal serum from different individuals can be distinguished on the basis of their cross-reactive antigen-binding properties. Furthermore the cross-reactive properties of lupus auto-antibodies may influence their capacity to form glomerular immune deposits.
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PMID:Cross-reactivity distinguishes serum and nephritogenic anti-DNA antibodies in human lupus from their natural counterparts in normal serum. 234 59

The Ku (p70/p80) autoantigen consists of two phosphoproteins of molecular mass approximately 70,000 and 80,000 forming a macromolecular complex that binds DNA. Autoantibodies from a patient with systemic lupus erythematosus were used to isolate cDNA clones encoding the human approximately 70-kDa Ku antigen (p70) from a lambda gt11 expression library. The deduced amino acid sequence of p70 consisted of 609 amino acid residues and was confirmed by partial amino acid sequencing. The protein contains two acidic domains of 61 residues (31% Glu + Asp) and 19 residues (53% Glu + Asp) that are similar in size and charge to those found in a number of proteins involved in transcriptional activation. The 61-residue acidic region is rich in serine, raising the possibility that its charge might be modulated by phosphorylation. The predicted amino acid sequence also contains two regions with periodic repeats of either leucine alone, or leucine alternating with serine every seventh position. The latter repeat displays sequence and secondary structural similarities with the "leucine zipper" regions of the c-myc and v-myc oncogene products. The p70 antigen does not appear to have extensive sequence homology with the 80-kDa Ku autoantigen based on analysis of RNA blots and immunological criteria. A major antigenic determinant or determinants recognized by human autoantibodies is located near a leucine repeat on the carboxyl-terminal 190 amino acid residues of p70.
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PMID:Molecular cloning of cDNA encoding the p70 (Ku) lupus autoantigen. 246 42

Autoantibodies to phospholipid antigens can be characterized using solid phase immunoassays to detect anticardiolipin antibodies (ACA) or in phospholipid-dependent clotting tests where lupus anticoagulant (LA) activity can be demonstrated. It has not been established whether each activity is due to the same or separate antibody subgroups. Plasma from two patients with high levels of both activities were used for purification of ACA and LA using sequential ion-exchange, gel-filtration, and anti-Ig affinity chromatography. Plasma could be separated into fractions containing each activity in the absence of the other. In these fractions, antibodies responsible for LA activity do not bind to isolated phospholipids in solid phase immunoassays, and conversely antibodies binding in these assays (ACA) do not possess LA activity, suggesting LA are directed against a more complex lipid epitope. In addition, in one patient ACA was of IgG isotype only, whilst LA was due to IgG and IgM isotypes. In this patient, the IgG-ACA was heterogeneous with three peaks clearly separated on ion-exchange chromatography. Affinity purified antiphospholipid antibodies have been previously prepared from a number of patients using a phosphatidyl-serine column and antibodies purified in this manner possess ACA but not LA activity. Taken together, these data indicate that tests for ACA and LA define separable subgroups of phospholipid binding antibodies, thus explaining the discordance often seen between the two activities.
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PMID:Anticardiolipin antibodies and lupus anticoagulants comprise separate antibody subgroups with different phospholipid binding characteristics. 251 85

In a study of connective tissue and infectious disease sera, we have demonstrated IgM and IgG anti-cardiolipin activity, in a solid phase radioimmunoassay, in systemic lupus erythematosus (SLE), rheumatoid arthritis, syphilis and in acute malaria caused by four different species of Plasmodium. The highest values were noted in SLE (IgM anti-cardiolipin P less than 0.005, IgG anti-cardiolipin P less than 0.01), but there was no correlation with anti-dsDNA, rheumatoid factor or VDRL titres in any disease group. Anti-cardiolipin binding was significantly associated with the lupus anticoagulant, thrombocytopenia, spontaneous abortions and thromboses in the SLE patients. Ten SLE sera from this thrombotic subset and 10 syphilitic sera with similar anti-cardiolipin activity, were tested against four phospholipid antigens and showed significantly different anti-phosphatidyl ethanolamine/anti-phosphatidyl serine binding ratios (P less than 0.001). These differences in phospholipid epitope specificity could explain the specificity of the VDRL antigen in syphilis serology, and we discuss a putative role for anti-phosphatidyl serine in the thrombotic diathesis of SLE.
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PMID:Anti-phospholipid antibodies in syphilis and a thrombotic subset of SLE: distinct profiles of epitope specificity. 257 56


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