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)

ADP-ribosylation reactions play a key role at several points in cellular regulation and repair of DNA damage. The use of polyclonal or monoclonal antisera to poly(ADP-ribose) as probes to localize the site(s) of action of the polymer offers a promising tool for these studies. We report here a simple, sensitive method for detection and titration of these antisera to poly(ADP-ribose) using nitrocellulose membrane (NC) as a support for a dot-blot analysis. We take advantage of the fact that a highly labeled poly(ADP-ribose) preparation can be obtained by incubation of a 0.3 M KCl extract prepared from calf thymus nuclei with 32P-NAD. Such a preparation of labeled antigen is used as a reagent to detect the positive antibody spots on the NC with negligible background. Subsequent titration of the antisera and their semi-quantitative evaluation are also feasible using the dot-blot method. The sensitivity of the assay is only limited by the specific activity that can be achieved for the labeled polymer prepared as the antigen probe. The advantage of this method is that it eliminates the need to prepare pure, highly radiolabeled polymer as well as the fact that several samples can be handled on the membrane simultaneously. We demonstrate application of this technique for screening sera from patients with systemic lupus erythematosus (SLE) for anti-poly(ADP-ribose) antibodies. Further, we also extend the use of these sera for immunoquantitation of ADP-ribosylated proteins in six human tumor cells in tissue culture.
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PMID:A dot-blot method for screening polyclonal and monoclonal antisera to poly(ADP-ribose). 249 84

Monoclonal and polyclonal anti-DNA antibodies from autoimmune mice, and experimentally induced rabbit anti-nucleic acid polyclonal antibodies were tested for stability of binding to nucleic acids in the presence of various concentrations of NaCl by an enzyme-linked immunosorbent assay (ELISA). Murine monoclonal antibodies 2C10 (IgG2b) and 1A2 (IgG2a), which are known to react specifically with double-stranded (ds) DNA, dissociated completely from their complexes with DNA when washed with a neutral 0.5 M NaCl solution. Another monoclonal antibody (MoAb) (IgM,kappa), polyreactive with single-stranded (ss) DNA, cardiolipin, and trinitrophenylhapten (TNP), was also dissociated from its complexes with ss DNA, but not from its complexes with TNP, by 0.3-0.5 M NaCl. Similar differences were observed in the binding stability of serum antibodies from autoimmune mice to DNA and TNP. In contrast, anti-nucleic acid polyclonal antibodies induced in rabbits by immunization with poly(I), poly(dT) or poly(ADP-ribose) were not significantly dissociated from their immune complexes with relevant antigens or DNA by 0.5 M NaCl. The finding that nucleic acid antigens were not detached from a solid phase by washing with 0.5 M NaCl solution indicated that the reduction of binding of anti-DNA antibodies in both MoAbs and naturally occurring antibodies was really due to dissociation of the antibodies from immune complexes. This is the first demonstration that DNA epitopes recognized by naturally occurring antibodies in both SLE and its mouse models are sensitive to neutral NaCl concentrations. This novel trait of naturally occurring antibodies will be very useful in studies on the nature of immune complexes in sera and kidneys of cases of systemic lupus erythematosus (SLE).
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PMID:A novel trait of naturally occurring anti-DNA antibodies: dissociation from immune complexes in neutral 0.3-0.5 M NaCl. 262 87

Anti-poly(ADP-ribose) antibodies were measured by an enzyme-linked immunosorbent assay (ELISA) in 6 pregnant women with systemic lupus erythematosus (SLE), 11 normal pregnant women and 6 randomly selected female SLE patients. Four pregnant SLE patients who had either an abortion after 13 weeks of gestation or a premature delivery showed very high titers of anti-poly(ADP-ribose) antibodies in week 8 of pregnancy. However, the titers of anti-poly(ADP-ribose) antibodies of all the normal pregnant women were similar to those of non-pregnant female SLE patients, being slightly higher than those of normal non-pregnant women. The isotype of anti-poly(ADP-ribose) antibodies in pregnant SLE patients was IgG, which did not crossreact with either DNA or cardiolipin. The number of pregnant SLE patients tested was small, but the coincidence of abortion with high titers of anti-poly (ADP-ribose) antibody was very close. Therefore, a high titer of anti-poly(ADP-ribose) antibody in pregnant SLE patients seems useful as an indicator of abortion or fetal distress.
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PMID:Antibody to poly(ADP-ribose) is an indicator of obstetric complications in pregnant patients with systemic lupus erythematosus. 276 23

Antibodies which bind to poly(ADP-ribose) have been described in Systemic Lupus Erythematosus (SLE) and a variety of infectious diseases. Two IgM kappa human monoclonal antibodies (MAbs), TH3 and PR4, produced from the fusion of peripheral blood lymphocytes of leprosy patients with the GM4672 lymphoblastoid cell line, were found to bind to poly(ADP-ribose) in direct binding and inhibition ELISAs. Significant inhibition of binding of these MAbs to poly(ADP-ribose) occurred with phenolic glycolipid-1, the M. leprae specific glycolipid, ssDNA, dsDNA, poly(dT), as well as poly(ADP-ribose) itself. Up to 80% of binding of TH3, and 90% of binding of PR4, to poly(ADP-ribose) was inhibited by 10 mcg of ssDNA suggesting that there may be sharing of some conformational determinants. Although the serological binding profiles of TH3 and PR4 are similar, only PR4 was found to bind to basal keratinocytes of normal human interfollicular epidermis and astrocyte cytoplasm in normal brain tissue. These results support the concept that an antibody binding site may accommodate more than one epitope. Furthermore, small differences in antigen binding potential may distinguish relatively innocuous antibodies from those which may be more pathogenic.
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PMID:Human monoclonal antibodies to phenolic glycolipid-1 from leprosy patients cross react with poly(ADP-ribose), polynucleotides and tissue bound antigens. 297 17

In order to determine whether environmental influence per se might influence autoantibody production, sera from the spouses of 20 SLE patients were examined. No antibodies to cardiolipin, poly (ADP-ribose), or ENA were detected and none had detectable rheumatoid factor. One weakly positive ANA reaction was noted, one had anti-DNA antibodies (by RIA and ELISA) and in two sera the common DNA antibody idiotype 16/6 was found. The idiotype was not, however, present on either anti-DNA or anti-K30 antibodies. Although long-term analyses are required, it is evident that sharing the same environment with patients who commonly express a wide range of autoantibodies and common idiotypes rarely leads to their expression in non-autoimmune subjects.
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PMID:A comparison of autoantibodies and common DNA antibody idiotypes in SLE patients and their spouses. 326 16

Human monoclonal antibodies (mAb) were produced by hybridomas derived from fusion of the GM4672 lymphoblastoid cell line and peripheral blood mononuclear cells from leprosy patients. Hybridoma supernatants were screened for immunoglobulin (Ig) secretion, binding to Mycobacterium leprae, phenolic glycolipid-I (Phen GL-I), the unique M. leprae glycolipid and single-stranded(ss)DNA by ELISA. On the basis of direct-binding ELISAs, two IgMk mAb (PR4 and TH3) were selected for characterization. PR4 and TH3 bound to M. leprae, Phen GL-I and ssDNA; PR4 also bound to M. avium and M. kansasii and TH3 to M. kansasii. Inhibition assays demonstrated that these antibodies did not bind to the terminal disaccharide of Phen GL-I. In addition, both PR4 and TH3 bound to several autoantigens: ssDNA, double-stranded(ds)DNA and poly(ADP-ribose) but not RNA. PR4 and TH3 were used for preparation of rabbit anti-idiotype antisera. Inhibition studies demonstrated that the affinity purified rabbit anti-idiotype antisera were specific for their respective idiotype and that both Phen GL-I and ssDNA inhibited binding of idiotype to its anti-idiotype. PR4, but not TH3, was found to be similar but not identical to the 16/6 idiotype originally identified on a human monoclonal anti-DNA antibody derived from a patient with systemic lupus erythematosus (SLE).
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PMID:Human monoclonal antibodies to phenolic glycolipid-I derived from patients with leprosy, and production of specific anti-idiotypes. 329 9

In pregnant autoimmune MRL/Mp-lpr/lpr (MRL/l) mice with many fetuses the level of anti-poly(ADP-ribose) antibodies was found to be the same as that of age-matched non-pregnant female mice, whereas in mice with few fetuses the level of anti-poly(ADP-ribose) antibodies was high in the early period of pregnancy and rapidly returned to control level at puerperium. The anti-poly(ADP-ribose) antibody that increased during pregnancy seemed to be mono-specific for its antigen, whereas the antibody that increased with age was polyspecific. The isotype/subclass of the former was mainly IgG2a. The marked increase in anti-poly(ADP-ribose) antibodies in the early period of pregnancy suggests endogenous sensitization to poly(ADP-ribose), which may be synthesized abnormally or stored during pregnancy, and is a predictive sign in pregnant lupus mice of a low litter size. This finding is applicable to pregnant patients with systemic lupus erythematosus (SLE); that is, it is a predictive sign of fetal loss and/or maternal risk. This was confirmed in the human cases examined so far.
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PMID:Antibody to poly(ADP-ribose) as a predictor of obstetric complications in autoimmune MRL/Mp-lpr/lpr mice: basis for its application to pregnant patients with systemic lupus erythematosus. 337 31

The genetic background of systemic lupus erythematosus (SLE) has been reexamined in a study of the serum of 31 lupus patients and 80 asymptomatic first degree relatives by measuring a common, cross reacting anti-DNA antibody idiotype designated 134, antibodies to poly(ADP-ribose), serum C3, circulating immune complexes, and antinuclear antibodies (ANA). Over 30% of the relatives had raised 134 and anti-poly(ADP-ribose) levels, and 9% had ANA titres greater than 1/20. In contrast, only one relative had a low serum C3 level. These results confirm that immunogenetic abnormalities associated with the production of autoantibodies and particular idiotypes must exist amongst lupus relatives as well as the patients. The production of autoantibodies, however, is not necessarily matched to the clinical expression of SLE.
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PMID:A study of anti-poly (ADP-ribose) antibodies and an anti-DNA antibody idiotype and other immunological abnormalities in lupus family members. 348 36

Anti-double stranded (ds) DNA antibodies in the sera of lupus-prone MRL/Mp-lpr/lpr (MRL/l) mice were determined by an enzyme-linked immunosorbent assay in parallel with anti-single stranded (ss) DNA, anti-left-handed Z-DNA and anti-poly(ADP-ribose) antibodies. The serum levels of these antibodies in these mice increased with age, and in particular anti-dsDNA antibodies appeared in mice more than 14 weeks old, along with progressive lymphadenopathy. We therefore established a hybridoma producing monoclonal anti-dsDNA antibody (2C10) from an 8-month-old MRL/l mouse. Monoclonal antibody 2C10 did not react with either poly(dT) or poly(I), which are major cross-reactants with previously reported monoclonal MRL mouse autoantibodies. Antibody 2C10 showed preference for phi X-174 replicative form DNA and calf thymus dsDNA over ssDNA. 2C10 idiotype (Id) was present in the sera of MRL/l mice, but only occasionally at high levels even in the aged mice tested. This result suggested that many Ids with anti-dsDNA antibody activity may contribute to lupus pathogenesis in this strain of mouse.
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PMID:A monoclonal anti-double stranded DNA antibody from an autoimmune MRL/Mp-lpr/lpr mouse: specificity and idiotype in serum immunoglobulins. 349 43

(C57BL/6 X DBA/2)F1 mice undergoing the graft-vs-host reaction (GVHR) produce autoantibodies after the injection of DBA/2 lymphoid cells. The anti-nuclear antibodies, including anti-poly (ADP-ribose) and anti-extractable nuclear antigens (ENA), in the sera of the autoimmune GVH F1 mice were investigated. Antibodies to double-stranded DNA, single-stranded DNA and ENA were predominantly IgG. In contrast, the autoantibodies to poly(ADP-ribose) were both IgG and IgM, although the former was predominant. These autoantibodies induced by the GVHR showed similar cross-reactivities with a number of nucleic acids to the monoclonal and some serum antinuclear antibodies derived from mice or humans with systemic lupus erythematosus (SLE). These results support the idea that GVH F1 mice are a good model of human SLE.
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PMID:Specificity of anti-nuclear antibodies induced in F1 mice undergoing the graft-vs-host reaction: isotypes and cross-reactivities. 349 93


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