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)

Serum autoantibodies to poly(ADP-ribose), single-stranded (ss) DNA and double-stranded (ds) DNA in 145 patients with systemic lupus erythematosus (SLE) were measured by an enzyme-linked immunosorbent assay (ELISA). The specificities of the antibodies for poly(ADP-ribose) or for ssDNA in 14 serum samples from different patients, who had relatively high antibody titers to either or both these antigens, were tested by competitive ELISA with poly(ADP-ribose) and ssDNA as inhibitors. The IgG class anti-poly(ADP-ribose) antibodies of 4 serum samples (cases 9, 11, 13 and 14) preferred poly(ADP-ribose) and those of 2 samples (cases 2 and 4) cross-reacted preferentially with ssDNA, while the IgG class anti-ssDNA antibodies of 2 serum samples (cases 9 and 11) significantly cross-reacted with poly(ADP-ribose). Hence, the nature of the antibodies to poly(ADP-ribose) in SLE patients seemed to be different from that of the anti-poly(ADP-ribose) antibodies in autoimmune MRL/Mp-lpr/lpr (MRL/l) mice, which seem to be subpopulations of anti-ssDNA antibodies and react equally well with poly(ADP-ribose) and ssDNA.
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PMID:Specificity of naturally occurring antibodies to poly(ADP-ribose) in patients with systemic lupus erythematosus: determination by an enzyme linked immunosorbent assay. 373 57

Monoclonal antibodies were prepared from C57/black mice which had been immunized with poly(ADP-ribose). As expected, some of these antibodies were very specific for poly(ADP-ribose) but, surprisingly, several bound to DNA as well. Analysis of the sera of these mice also showed elevated levels of antibodies to DNA. Monoclonal antibodies against poly(ADP-ribose) were also recovered from unimmunized NZB/W mice which provided an animal model for systemic lupus erythematosus(SLE). These antibodies also cross-reacted with DNA. Comparison of the specificities of the monoclonal antibodies from the two groups of mice showed some striking similarities. In particular, three out of 11 antibodies from the C57/black mice preferred poly(dT) as judged by a solid phase radioimmunoassay. Similarly, 10 out of 17 antibodies from the NZB/W group showed the same type of specificity pattern. These results demonstrate that anti-DNA antibodies can be induced by poly(ADP-ribose) and that some of the autoimmune DNA-binding antibodies found in SLE may result from exposure to poly(ADP-ribose).
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PMID:The production of antibodies to DNA in normal mice following immunization with poly(ADP-ribose). 379 91

Poly (ADP-ribose) and dsDNA binding activity have been measured in sera from 61 patients with systemic lupus erythematosus (SLE) and 188 control sera from 20 normal individuals, 144 patients with clinically similar diseases and 24 patients with drug-induced anti-nuclear antibodies (ANA). Elevated poly (ADP-ribose) binding was not observed with normal sera. Five of 144 samples from diseases entering the differential diagnosis of SLE gave raised poly (ADP-ribose) binding compared with 12 in the 125I-dsDNA binding. Only two of these false positive samples gave elevated binding in the 14C-dsDNA assay. The apparent high specificity of the poly(ADP-ribose) assay was not observed with samples containing drug-induced ANA where 62% had elevated binding values. The frequency with which the poly(ADP-ribose) assay was positive with SLE sera (sensitivity) was lower than either of the dsDNA assays. This low sensitivity and the high rate of false positives in patients with drug-induced ANA limit the value of the poly(ADP-ribose) assay as a diagnostic test for SLE. However the restriction of poly(ADP-ribose) antibody to SLE and patients with drug-induced ANA together with the known role of poly(ADP-ribose) in DNA excision repair suggest that the antibody may be of fundamental significance.
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PMID:Measurement of antibody to poly (adenosine diphosphate-ribose): its diagnostic value in systemic lupus erythematosus. 661 May 11

A simple and sensitive method was developed for detection of antibodies to histones using a modification of the enzyme-linked immunosorbent assay (ELISA) for antibodies to nucleic acids. The antigens used for antibody assay were poly(ADP-ribose), left-handed Z-DNA, double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), and calf thymus histones. These five antigen-antibody systems were used to examine the antibodies in patients with systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS). A positive correlation was found between the antibody titers in patients with PSS. However, weak correlation was found between the titers of antibodies to these nuclear antigens in the SLE patients, except for correlations between the titers of antibodies to left-handed Z-DNA and histones, and those to ssDNA and dsDNA. From these data, it is suggested that presentation of modified chromatin to immune systems is involved in antinuclear antibody formation in PSS patients, whereas spontaneous expansion of clones for antinuclear antibodies may occur in SLE patients under certain conditions.
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PMID:Profiles of antibodies to poly(ADP-ribose), left-handed Z-DNA, and other nuclear constituents in systemic lupus erythematosus and progressive systemic sclerosis. 665 33

Sera from 41 patients with systemic lupus erythematosus (SLE), 87 controls with various diseases, and 30 normal subjects were examined for poly (adenosine diphosphate-ribose) and ds DNA binding. Elevated levels of poly (ADP-ribose) binding were found in 73% of the SLE patients compared with 58% who had raised ds DNA binding. In a further study of 160 sera from 27 patients with SLE, levels of antipoly (ADP-ribose) antibodies were shown to correlate with clinical activity better than either anti-ds DNA or ss DNA antibodies.
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PMID:Studies on autoantibodies to poly (adenosine diphosphate-ribose) in SLE and other autoimmune diseases. 698 86

A simple and rapid microenzyme-linked immunosorbent assay has been developed for determination of anti-poly(ADP-ribose) antibodies in humans using a combination of protein A-alkaline phosphatase conjugates and poly(ADP-ribose)-coated polyvinyl microplates. After a 1-h treatment of the plates with 100 microliters of poly L-lysine (PLL) solution (50 micrograms/ml), an aliquot of the solution containing 100 ng poly(ADP-ribose) (50 microliters) was added to the PLL-treated plates and evaporated at 37 degrees C overnight to facilitate the adherence of poly(ADP-ribose) to the plates. Nonspecific binding of diluted test sera from patients with systemic lupus erythematosus (SLE) or from normal individuals to the PLL-coated plates was minimized by exposure of the plates for 1 h to Tris-buffered saline (pH 7.4) containing 0.01% bovine serum albumin (BSA). This method was also applicable to the determination of anti-double-stranded DNA antibodies in humans. The present assay is advantageous over those reported so far as it saves time and antigen.
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PMID:A simple and rapid microenzyme-linked immunosorbent assay for antibodies to poly(ADP-ribose) in systemic lupus erythematosus. 714 14

Two human IgM lambda monoclonal antibodies (MAb) derived from the splenic lymphocytes of patients with idiopathic thrombocytopenia (Ben) and systemic lupus erythematosus (Wri) were studied. BEN-27 and WRI-170 hybridoma supernatants were screened for binding to ssDNA, dsDNA, poly (ADP-ribose), cardiolipin, histone subclasses and Klebsiella K30 cell wall antigen. Of this panel of antigens, BEN-27 and WRI-170 antibodies reacted only with histone H1. Their fine specificity was defined by direct and inhibition ELISA with synthetic peptides of the major human H1b variant. Antibody WRI-170 was shown to bind to both the N- and C-terminal peptides encompassing residues 1-16 and 204-218 of H1b whereas BEN-27 reacted only with peptide 204-218. To analyse the genetic origin of these autoantibodies, we determined the nucleotide sequence of the heavy (H) and light (L) chain variable regions of these two hybridomas. BEN-27 and WRI-170 MAbs were found to use VH1-DN1-JH4/V lambda 3-J lambda 2 and VH3-DIR2-D21/9-JH1/V lambda 2-J lambda 2 gene segment combinations respectively. Between 70 and 95% homology was demonstrated when the mRNA sequences for BEN-27 and WRI-170 were compared with published VH and V lambda germline sequences. This finding suggests that BEN-27 heavy and light chains and WRI-170 light chain use unidentified VH and V lambda germline gene segments whereas WRI-170 heavy chain derives from a VH gene segment recently identified. It is noteworthy that the CDRs of the two MAbs contain several negatively charged amino acids which are assumed to be of critical importance in antigen binding. Moreover, striking similarities are observed between BEN-27 heavy chain CDR2 and a previously described murine anti-H1 Ab heavy chain CDR2.
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PMID:Sequence analysis and fine specificity of two human monoclonal antibodies to histone H1. 751 Dec 11

The prescription drugs procainamide (PA) and hydralazine (HYD) are associated with the induction of autoimmunity and a clinical syndrome called drug-induced lupus. Since PA- and HYD-induced autoantibodies are directed primarily against histones and histones are prime acceptors of poly (ADP-ribose) (PADPR), we have investigated the effects of PA and HYD on the activity of poly (ADP-ribose) polymerase (PADPRP). Control substances, with structures similar to PA and HYD but not known to induce lupus, included N-acetylprocainamide (NAPA) and the amino acids phenylalanine, tryptophan and proline, and their amide derivatives. Wil-2 cells were incubated in 0.5-50 microM PA, NAPA and HYD, which included therapeutic concentrations of these drugs. The mean enhancement of incorporation of [3H]-nicotinamide adenine dinucleotide (NAD) into PADPR was 1.84 (P = 0.005) with PA, with HYD 1.48 (P = 0.029), and with NAPA 1.38 (P = 0.036). This increase was suppressed by 3-aminobenzamide, an inhibitor of PADPRP activity. Little or no increase in [3H]-NAD incorporation was observed with equivalent concentrations of phenylalanine, phenylalaninamide or tryptophan. However, a 1.29-fold increase was noted with 0.5 microM tryptophanamide, a 1.26-fold increase with 0.5 microM prolinamide and a 1.4-fold increase with 50 microM proline. PA increased PADPRP activity in B- and T-cell lines but not in promyelocytic leukemia or epithelial cell lines. Since poly (ADP-ribosylation) is important in the cellular response to various agents, the increased ADP-ribosylation of intracellular molecules may be a key event in the induction of autoantibodies.
Lupus 1993 Jun
PMID:Effect of procainamide and hydralazine on poly (ADP-ribosylation) in cell lines. 769 Feb 94

Poly(ADP-ribose) metabolism is altered in patients with SLE. In order to localize the defect, the levels of poly(ADP-ribose) polymerase-specific mRNA were measured from dot blots of total RNA from peripheral blood lymphocytes. In this preliminary study, eleven patients with SLE and two with antiphospholipid syndrome were compared to three controls. It was found that the mean levels of specific mRNA were ten fold lower in the PBL from SLE patients compared to controls and no overlap of values was seen between the two groups. No such decrease was seen in the PBL from the patients with antiphospholipid syndrome. It is concluded that the defect in poly(ADP-ribose) polymerase metabolism that is seen in SLE patients occurs at the level of transcription or mRNA turnover.
Lupus 1994 Apr
PMID:Decreased mRNA levels coding for poly(ADP-ribose) polymerase in lymphocytes of patients with SLE. 792 Jun 10

Antiphospholipid antibodies (aPL) are associated with neurological diseases such as stroke, migraine, epilepsy and dementia and are thus associated with both vascular and non-vascular neurological disease. We have therefore examined the possibility that these antibodies interact directly with neuronal tissue by studying the electrophysiological effects of aPL on a brain synaptosoneurosome preparation. IgG from patients with high levels of aPL and neurological involvement was purified by protein-G affinity chromatography as was control IgG pooled from ten sera with low levels of aPL. Synaptoneurosomes were purified from perfused rat brain stem. IgG from the patient with the highest level of aPL at a concentration equivalent to 1:5 serum dilution caused significant depolarization of the synaptoneurosomes as determined by accumulation of the lipophylic cation [3H]-tetraphenylphosphonium. IgG from this patient as well as IgG from two elderly patients with high levels of aPL were subsequently shown to permeabilize the synaptosomes to labeled nicotinamide adenine dinucleotide (NAD) and pertussis toxin-ADP-ribose transferase (PTX-A protein) as assayed by labeled ADP-ribosylation of G-proteins in the membranes. No such effects were seen with the control IgG. aPL may thus have the potential to disrupt neuronal function by direct action on nerve terminals. These results may explain some of the non-thromboembolic CNS manifestations of the antiphospholipid syndrome.
Lupus 1999
PMID:Antiphospholipid antibodies permeabilize and depolarize brain synaptoneurosomes. 1019 7


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