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)

A simple and practical microhemagglutination test that detects two antibodies, one showing reactivity to the DNA moiety of soluble nucleoprotein (sNP) and the other to the DNA-histone complex of sNP, is described. The method incorporates human erythrocytes formalinized at 30 C., tanned, and coated with sNP at 37 C. Antibody specificity was determined by inhibition experiments performed on sera with added DNA or sNP antigen. With the indirect LE cell technic, evidence that the anti-sNP antibody detected in this work is related to the serum LE factor commonly associated with the LE cell phenomenon was obtained. The hemagglutination test is helpful in establishing the specific diagnosis of systemic lupus erythematosus (SLE) and may be used to follow the course of the disease and response to therapy in SLE patients, as this is a semiquantitative technic and rise or fall in titer or antibody can be determined.
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PMID:Microhemagglutination test for the detection of nucleoprotein antibody in systemic lupus erythematosus. 5 Jul 28

It was attempted to evaluate passive haemagglutination of antigen coated, tanned erythrocytes as a test by which to demonstrate anti-DNA in systemic lupus erythematosus. The antigens was prepared using a minimum of procedures in order to produce a native preparation. The resulting material had most of the criteria applying to native DNA, but the protein content was about 9%. It contained a thymocyte specific component, but no demonstrable trace of bovine species antigen. The reactions between the antigen and an anti-DNA serum from a patient with suspected SLE were inhibited by DNA and DNA-histone, but not appreciably by ENA, RNA or desoxyribonucleosides. Passive haemagglutination reactions against the antigen were positively correlated to a homogeneous immunofluorescence nuclear pattern and negatively correlated to a speckled pattern. Passive haemagglutination titres against ENA and DNA antigen were not correlated. Seventy-three per cent of randomly selected sera gave either purely DNase sensitive reactions (19%) or reactions of combined sensitivity to DNase and other enzymes. Twenty-eight out of 53 sera reacting in the passive haemagglutination test reacted also in the immunofluorescence test against Chrithidia luciliae kinetoplasts. The latter reactions were DNase sensitive. It applies to both tests that DNase sensitive, but RNase resistant, reactions were well correlated, irrespective of their sensitivity to trypsin while DNase resistant or DNase and RNase sensitive reactions were not correlated. The passive haemagglutination test using a native but relatively crude DNA-preparation coated on tanned sheep erythrocytes supplemented by specificity tests with DNase and RNase treated antigen gives about the same information as the indirect immunofluorescence test against Chrithidia luciliae kinetoplasts. Furthermore, the results show that patients' sera reacting with a homogeneous nuclear pattern in the indirect immunofluorescence test may contain not only anti-DNA and anti-nucleohistone antibodies, but also antibodies to a number of non-histone chromatin associated proteins some of which contain RNA.
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PMID:Antigenic properties of a DNA-preparation from calf thymus used for the demonstration of anti-DNA. 6 25

When tissue sections are extracted with 0.1 N HCl, cellular nuclear proteins, including histones, are removed but nuclear DNA is retained. Histones can be reconstituted back to nuclear DNA in acid-extracted tissue sections so that the resulting nuclear substrate is composed only of DNA and histones and does not contain acidic nuclear protein antigens. The resulting DNA-histone tissue substrate can be used in the immunofluorescent method for specific detention of antibodies to histones. Sera from 23 patients with drug-induced lupus erythematosus (procainamide 19, isoniazid 2, nitrofurantoin 2) and 20 patients with idiopathic (not drug-induced) systemic lupus erythematosus (SLE) were studied. All 23 patients with drug-induced lupus erythematosus (LE) lost nuclear staining on acid-extracted sections. In contrast, only 12 of 20 with idiopathic SLE lost nuclear staining on acid-extracted tissues, and in the remaining 8, there was no significant fall in titer. In the drug-induced LE group, loss of nuclear staining was due to the absence of histones on the substrate because with histone-reconstituted sections, 22 of 23 again became positive for nuclear staining at titers equal to or at one doubling dilution below titers on unextracted tissues. In contrast, of the 12 idiopathic SLE sera which lost nuclear staining, only 5 regained nuclear staining on histone-reconstituted tissue sections. In idiopathic SLE, antinuclear antibodies are heterogeneous in specificities and may consist of antibodies to native DNA, histones, or nonhistone proteins. In contrast, antinuclear antibodies in drug-induced LE are less heterogeneous and mainly consist of antibodies to histones.
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PMID:Antibodies to histones in drug-induced and idiopathic lupus erythematosus. 35 49

Antibodies to histones were investigated in the serum of forty-five patients with spontaneously occurring systemic lupus erythematosus (SLE) who were not receiving any form of treatment. Twenty-three had active and twenty-two had inactive disease. Thos with active disease were also studied after the initiation of corticosteroid treatment to determine the effect of treatment on anti-histone antibodies. Both a complement fixation method and indirect immunofluorescence of acid-eluted histone-reconstituted tissue sections were used, with excellent correlation between these two methods. Eleven of the forty-five SLE patients, but none of forty-five normal controls had antibodies to histone. Untreated patients with active and inactive disease had a similar incidence of antibodies to histone. They disappeared, however, soon after the initiation of treatment in the patients with active disease. Patients with antibodies to histones had a higher prevalence of cutaneous vasculitis, anaemia, lupus nephropathy and Raynaud's phenomenon, but a lower prevalence of lupus brain involvement than those without such antibodies. Only the latter, however, reached statistical significance.
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PMID:Antibodies to histones in systemic lupus erythematosus. 38 Aug 54

A high prevalence of antibodies to double-stranded DNA (AbDNAds) has been recently reported in serum of patients with autoimmune thyroid disorders, but the specificity of this finding has been questioned. For this reason, the prevalence of several antibodies to DNA-related nuclear antigens (AbDRENA) has been evaluated in sera of patients with autoimmune and non-autoimmune thyroid disease. The study group included: 46 Graves' disease patients, 28 Hashimoto's thyroiditis patients, 25 patients with toxic nodular goitre and 11 with non-toxic nodular goitre. Twenty-eight Graves' patients were retested during methimazole (MMI) therapy, and 5 after radioiodine administration. Twenty-two patients with systemic lupus erythematosus and 28 normal subjects served as positive and negative controls, respectively. AbDRENA included: AbDNAds by RIA or immunofluorescence (IF); antibodies to single-stranded DNA (AbDNAss) and antibodies to histone (AbHist) by ELISA methods; antibodies to nuclear antigens (ANA) by immunofluorescence. RIA values were considered to be abnormal when 2 SD above the mean of normal controls. In our study 13% of Graves' patients were positive for AbDNAds by RIA: all of them had negative tests by IF; 11% were positive for AbDNAss, 2% for AbHist and 7% for ANA. A comparable prevalence of positive results for AbDNAds by RIA, with negative IF tests, was found in Hashimoto's thyroiditis patients. No significant changes of antibody levels were observed in Graves' patients during MMI treatment or after radioiodine administration. A positivity for AbDNAds or AbDNAss was found in 8% of patients with toxic nodular goitre, but in none of those with non-toxic goitre.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Circulating antibodies to DNA-related antigens in patients with autoimmune thyroid disorders. 129 45

Systemic lupus erythematosus (SLE) is the archetypic non-organ specific autoimmune disease in which polyclonal B-cell activation is reflected by the wide range of auto-antibody specificities. Among these, anti-ds DNA antibodies bear special significance since they are disease specific, tend to occur at high titers in an active clinical state and are considered to be pathogenic through immune complex formation. However, data accumulated in the last few years have led to a somewhat more complex view of anti-DNA autoantibodies and SLE pathogenesis. For instance, the definition of pathogenic subpopulations of anti-DNA antibodies is an important question which has been addressed in terms of isotypes, idiotypes and DNA sequences of antibodies. Also, some of the cross reactivities described with monoclonal anti-DNA antibodies appear to be due to the formation of immune complexes with DNA, histones or nucleosomes. In addition, anti-DNA-nucleosome immune complexes can react with the cell membrane. These findings indicate that not only DNA but also the nucleosome as a multimolecular complex or its non-DNA component, i.e. histone, may be viewed as relevant target autoantigens in SLE. This review will focus on experimental data supporting this new representation of this set of autoantibodies directed against DNA, histone and the nucleosome, and their possible intervention in SLE pathogenesis.
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PMID:Anti-DNA antibodies and their relationships with anti-histone and anti-nucleosome specificities. 134 83

MRL/Mp(-)+/+ mice produce antinuclear antibodies and develop a spontaneous autoimmune syndrome with lupus-like nephritis. We obtained a panel of seven histone-reactive IgG mAb from a single MRL/Mp(-)+/+ mouse. These antibodies do not react significantly with DNA or individual histones, but bind strongly to the histone H2A-H2B dimer and even more strongly to the H2A-H2B-DNA complex. These antibodies also bind to whole nuclei when tested by immunofluorescence, indicating that they recognize an epitope accessible in chromatin. The V region sequences of these antibodies have been determined. The H chain third complementarity-determining regions of these antibodies are similar to those found in anti-DNA antibodies even though the antibodies in our panel do not react with DNA in the absence of histones, suggesting that DNA is part of the subnucleosome epitope. Several of these antibodies are clonally related, supporting the hypothesis that the activation of these clones is Ag-driven. Analysis of the sequences of these antibodies indicates that they derive from autoreactive B cells that were clonally expanded and whose V region genes have undergone numerous somatic mutations.
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PMID:Monoclonal autoantibodies to subnucleosomes from a MRL/Mp(-)+/+ mouse. Oligoclonality of the antibody response and recognition of a determinant composed of histones H2A, H2B, and DNA. 137 30

IgG reactivity with the (H2A-H2B)-DNA complex, a subunit of the nucleosome, has been detected in many patients with lupus induced by procainamide and quinidine, but the similarity among the epitopes targeted by these antibodies in this heterogeneous patient group as well as the prevalence of this specificity in lupus induced by other drugs is unknown. Studies with histone-DNA complexes formed by sequential addition on a solid phase demonstrated that complexes containing single histones had negligible antigenicity, indicating that DNA stabilizes a protein epitope in the H2A-H2B dimer or that the complete epitope is generated by a surface feature involving H2A-H2B and DNA. F(ab')2 isolated from a patient with procainamide-induced lupus blocked greater than 90% of the anti-[(H2A-H2B)-DNA] reactivity in six of six sera from patients with lupus induced by procainamide, four of four quinidine-induced patients and in sera from patients with lupus induced by acebutolol, penicillamine, and isoniazid, but not methyldopa or auto-antibodies to the component macromolecules. Fab fragments purified from the IgG of two quinidine-induced lupus patients and patients with isoniazid- and procainamide-induced lupus retained 39% +/- 8% of their original IgG reactivity compared to 34 +/- 28% of the original anti-tetanus toxoid activity of Fab fragments in two of the same sera and two normal sera. These results indicate that anti-[(H2A-H2B)-DNA] does not require divalent antigen-antibody complexes for stability, and that the complete epitope is created by the monomeric, trimolecular histone-DNA complex. We conclude that despite their pharmacologic and chemical heterogeneity, many lupus-inducing drugs elicit near identical autoantibodies.
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PMID:Autoantibodies associated with lupus induced by diverse drugs target a similar epitope in the (H2A-H2B)-DNA complex. 137 52

Genetic regulation of the spontaneous anti-histone antibody production in systemic lupus erythematosus (SLE) was studied using the H-2-congenic and T cell receptor beta chain gene complex (TCR beta)-congenic NZB and NZW strains and their crosses. We found that the original, parental H-2d/d NZB mice produced significantly higher titers of serum IgM class anti-histone antibodies than did the congenic H-2d/z or H-2z/z NZB mice. However, none of these three NZB strains produced IgG antibodies. The NZW strain of any H-2 haplotype did not produce IgM and IgG anti-histone antibodies. The IgG anti-histone antibodies were produced only by H-2d/z heterozygous NZB x NZW F1, but not by homozygous H-2z/z or H-2d/d NZB x NZW F1 mice. In studies using (NZB x NZW) F1 x NZB backcross mice, only the progeny having both H-2d/z and NZW-type TCR beta genotypes produced high amounts of IgG antibodies. There was a tight linkage between the NZW-type TCR beta and the production of IgG anti-histone antibodies in TCR beta-congenic NZB x NZW F1 mice. All these findings were in keeping with our preceding observations on the genetic regulation of anti-DNA antibodies in these mice and suggest that certain common mechanisms such as super-antigen-mediated or common idiotope-mediated regulations may underlie the production of these two distinct autoantibodies in NZB x NZW F1 mice.
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PMID:Genetic association between natural autoantibody responses to histones and DNA in murine lupus. 139 98

The rate of clearance of extracellular plasma DNA in man has important implications for pathogenetic mechanisms in systemic lupus erythematosus (SLE), as well as for certain other clinical states. Present knowledge of this parameter is derived exclusively from studies of injected, naked DNA in animals. Recent information indicates that the physiologic form of plasma DNA in SLE is that of oligonucleosome-like molecules rather than of naked DNA and consists of multimeric complexes of DNA bound to histone, probably arising from an apoptotic process. In order to study the rate at which these oligonucleosome-like complexes are removed from plasma and to do so in man rather than experimental animals, we exploited the observation that during haemodialysis large amounts of DNA are released, apparently within the dialysis coil, into the patient's plasma. Since this release appears to cease promptly with termination of the procedure, it offered the potential for estimating the rate of removal of such DNA from human plasma. Moreover, if that DNA, as postulated, were shown to possess an oligonucleosome-like structure resembling that found endogenously in human SLE, the relevance of such information to the human disease state would be further enhanced. The present results support the conclusion that DNA released into plasma during haemodialysis possesses such an oligonucleosome-like structure. The plasma half-life of that DNA in man was found not to exceed 4 min. The highly dynamic state thus implied for extracellular endogenous plasma DNA in man has important implications for pathogenetic mechanisms dependent on dsDNA in SLE. Moreover, individuals undergoing chronic haemodialysis, who are thereby exposed to a very large cumulative amount of such DNA, might serve as models for studying its long-term sequelae.
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PMID:Haemodialysis as a model for studying endogenous plasma DNA: oligonucleosome-like structure and clearance. 139 1


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