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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study of patients with systemic lupus erythematosus revealed the close association of the disease with measles--or a related virus. High titres of antibodies to measles virus were found in patients that correlated with the course of the disease. Immunofluorescence tests revealed measles virus or a related antigen in lupus-affected tissues. Inclusion bodies consisting of paramyxovirus-like ribonucleoprotein structures were regularly detected in both affected tissues and leukocytes. Molecular hybridization of measles virus RNA with DNA from the affected tissues showed that DNA transcripts of measles or a closely related virus are integrated in the cellular nuclear DNA. Possible pathogenetic mechanisms of the disease are discussed.
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PMID:Molecular pathogenesis of systemic lupus erythematosus. 109 Dec 37

Human lysosomes were isolated from normal peripheral blood leukoyctes and characterized by electron microscopy, enzyme analysis, and assays for DNA and RNA. Stored sera from 37 unselected patients with systemic lupus erythematosus (SLE), including active and inactive, treated and untreated cases, were tested in complement fixation (CF) reactions with these lysosome preparations. 23 SLE sera exhibited positive CR reactions, as did sera from two patients with "lupoid" hepatitis. The seven SLE sera with strongest CF reactivity also demonstrated gel precipitin reactions with lysosomes. Neither CF nor precipitin reactions with lysosomes were observed with normal sera or with sera of patients with drug-induced lupus syndrome, rheumatoid arthritis (RA), polymyositis, or autoimmune hemolytic anemia. By several criteria the antilysosome CF and precipitin reactions of SLE sera cound not be attributed to antibody to DNA, RNA, or other intracellular organelles. The lysosomal component reactive with SLE sera in CF assays was sedimentable at high speed and is presumably membrane associated. The CF activity of two representative SLE sera was associated with IgG globulins by Sephadex filtration. A search for lysosomal antigen in SLE and related disorders was also made. By employing rabbit antiserum to human lysosomes in immunodiffusion, a soluble lysosomal component, apparently distinct from the sedimentable (membrane-associated) antigen described above, was identified in serum, synovial fluid, or pleural fluid from patients with SLE, RA, ankylosing spondylitis, and leukemoid reaction. An antigenically identical soluble component reactive with the rabbit antiserum could be released in vitro from intact lysosomes by repeated freeze-thaw cycles..
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PMID:Studies with human leukocyte lysosomes. Evidence for antilysosome antibodies in lupus erythematosus and for the presence of lysosomal antigen in inflammatory diseases. 109 14

In 50 to 60 percent of patients with systemic lupus erythematosus (SLE), a band of immunoglobulins beneath the epidermis of visibly normal skin. This highly specific finding has been used as a diagnostic test (Lupus Band Test) for SLE. Similar immunoglobulin deposits are found in an inbred strain of New Zealand mice which spontaneously develop an autoimmune disease with many features of SLE. Subepidermal immunoglobulin deposits are found most frequently in SLE patients with proliferative glomerulonephritis, hypocomplementemia, and serum antibodies to native DNA (anti-nDNA). When anti-nDNA levels are suppressed by cyclophosphamide, these deposits disappear. The subepidermal accumulation of immunoglobulin in SLE patients and in the mouse model apparently depends on the presence of antibody to native DNA. It is proposed that serum anti-nDNA precipitates with nDNA which is released locally from epidermal nuclear breakdown.
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PMID:The significance of cutaneous immunoglobulin deposits in lupus erythematosus and NZB/NZW F1 hybrid mice. 109 41

A prospective, randomized drug trial compared prednisone (60 mg per day initially) to azathioprine (3 to 4 mg/kg of body weight - day initially) plus prednisone in 24 patients with life-threatening systemic lupus erythematosus. Each group contained patients matched for age, sex, disease duration, previous therapy, and clinical and laboratory features of lupus erythematosus. During a mean follow-up period of 18 to 24 months, there were no significant differences between the two groups in number of deaths, renal or extrarenal manifestations of disease, serum complement levels, DNA antibodies, antinuclear antibody titers, lupus erythematosus cells, or Coombs' antibodies. There was no convincing evidence of a steroid-sparing effect of azathioprine. Side effects attributable to steroids were equally common in both groups; infections were not increased in the combination therapy group. Azathioprine was hepatotoxic in doses of 200 mg daily or more. Azathioprine was not a useful adjunct to corticosterolds in short-term therapy of a small number of patients with severe systemic lupus.
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PMID:Azathioprine plus prednisone compared with prednisone alone in the treatment of systemic lupus erythematosus. Report of a prospective controlled trial in 24 patients. 110 77

A technique is described for using radiolabeled RNA complementary to human DNA as a probe for the specific identification of submicrogram concentrations of human DNA by formation of RNA-DNA hybrids. An example is given of its application to the semiquantitation of human DNA in human plasma, a substance that is ordinarily difficult to examine because materials are present that interfere with the usual colorimetric or fluorometric assays. An example is also given of the use of an analogous approach to analyzing rabbit serum for circulating bacterial DNA. Unique to the hybridization technique is a degree of specificity sufficient to identify specific base sequences and hence the origin of the DNA being detected, a point that may be important in the examination of circulating DNA reported to occur in patients with systemic lupus erythematosis. This technique may also be of value in clarifying the presently conflicting data regarding the occurrence of free DNA in the normal human circulation.
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PMID:Use of nucleic acid hybridization for specific detection of submicrogram quantities of DNA, and its application to human plasma. 111 52

This study demonstrates that in systemic lupus erythematosus (SLE), the presence of immune complexes on the glomerular basement membrane (GEM) does not invariabley result in histological and/or functional lesions of the kidney. Among a group of 29 lupus patients, six subjects were selected for thorough investigation, because their renal function was normal or only slightly altered though they had suffered from SLE for 20 months to 18 years. All patients had antinuclear factor, anti-native-DNA antibody and a low level of complement; 3 had anti-denatured-DNA antibody, 2 had denatured DNA-anti-denatured-DNA circulating complexes and 3 had anti-RNA-protein antibody. Kidney biopsies disclosed either no histological lesion or minimal changes in five of them and diffuse proliferative glomerulonephritis in one. By contrast, using the immunofluorescent technique, granular deposits containing the third component of complement (C3) were found on the GBM of all patients; IgG was present in 5 cases, IgM in 3, fibrinogen in two cases and around the tubules of one. Electron microscopy confirmed the presence of subendothelial and mesangial deposits. Our results also showed a good correlation between the importance of deposits and the presence of denatured DNA-anti-denatured-DNA circulating complexes. From the data obtained in these 6 cases as well as in the 23 other patients of the group, 3 categories of lupus patients could be distinguished with regard to kidney involvement: 1) patients with insignificant histological lesions, no immune deposits and essentially normal function; 2) patients with definite histological lesions, immune deposits and renal insufficiency and 3) patients with few if any histological lesions and little functional impairment contrasting with important immune deposits. The resistance of some patients to the mephrotoxic effects of immune deposits shows that lupus nephritis depends on intricate pathogenic mechanisms and suggests that these are possible antagonized by "protective" factors.
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PMID:Immune complex deposits in systemic lupus erythematosus kidney without histological or functional alterations. 114 88

An autoimmune response to certain nuclear antigens frequently develops in patients receiving prolonged therapy with procainamide. In order to define events involved in the initiation of this immune response, patients with myocardial infarction were studied early after starting procainamide and at later times. Polynucleotide antibodies and circulating polynucleotide antigens were sought by sensitive assay techniques in the sera of these patients. Very high titers of antiribonucleoprotein developed selectively in the majority of these patients after short-term therapy with procainamide. Such antibodies were infrequent in the long-term therapy group, most of whose members exhibited anti-single-strand DNA and were symptomatic with overt procainamide-induced lupus. Patients with acute myocardial infarction who did not receive procainamide did not develop anti-polynucleotide antibodies, but rather had high levels of free ribonucleoprotein antigen in their serum. Various interpretations of these data are discussed.
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PMID:Development of antibodies to ribonucleoprotein following short-term therapy with procainamide. 120 Nov 4

The time course of DNA binding capacity (DNA-bc) was found to correlate with the clinical course in a group of 21 patients who had biopsy-proven lupus glomerulonephritis and were treated with immunosuppressive agents. Eight patients showed a sequential DNA-bc pattern in which a high titre of anti-DNA antibody was present for a prolonged period of time all having an unfavourable clinical course. Persistently high values of DNA-bc preceded by as much as 10 months evidence of renal deterioration obtained by conventional renal function tests. Thirteen patients showed a low titre of anti-DNA antibody throughout most of their course, 12 having a favourable outcome. An initially high value of DNA-bc had no prognostic significance. These results suggest that the persistence of a high titre of anti-DNA antibody in patients with lupus glomerulonephritis is a poor prognostic sign.
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PMID:Prognostic significance of DNA-binding capacity patterns in patients with lupus nephritis. 122 25

Virtually all preparations of DNA used to detect antibody to native DNA (nDNA) by binding assays have been found to be subtly contaminated by single stranded DNA. Because recent DNA binding data have directly challenged the unique role previously attributed to these antibodies in systemic lupus erythematosus (SLE), resolution of the consequent ambiguity is of theoretical and practical importance. It is proposed that a synthetic nDNA molecule (dAT) might circumvent this difficulty by being antigenically equivalent to nDNA while, on theoretical grounds, lacking significant contamination with single stranded DNA or other cellular antigens. These expectations were generally confirmed by biochemical and immunological analyses. In clinical studies, sera from 124 pateints with SLE and from controls were examined for their ability to bind dAT. In contrast to results with KB binding, patients with non-SLE rheumatologic disorders were indistinguishable from normals by dAT binding. dAT binding was elevated in 85% of sera from SLE patients with clinically-judged active nephritis but in only 9% of those with inactive renal disease. Active non-renal disease, including cerebritis, was not associated with increased dAT binding. Individual non-lupus sera which bound increased amounts of KB DNA, failed to bind dAT. It is suggested that such binding resulted from contaminating non-nDNA antigens. When elevated, dAT binding, like KB binding, varied with disease activity and might thus be useful as a parameter thereof. In several patients elevated dAT binding led to the finding, on biopsy, of clinically silent, active, diffuse proliferative nephritis. It is concluded that use of synthetic nDNA antigens such as dAT may offer theoretical and practical advantages over naturally-derived preparations in detecting anti-nDNA, both clinically and for investigational purposes. Also, caution is urged in interpreting DNA binding data derived from incompletely characterized systems, particularly with regard to the occurrence of anti-nDNA antibodies in serum.
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PMID:Detection of anti-DNA antibody using synthetic antigens. Characterization and clinical significance of binding of poly (deoxyadenylate-deoxythymidylate) by serum. 126 74

The frequency and the specificities of antinuclear antibodies (ANAb) were studied in dogs with systemic lupus erythematosus (SLE) and compared to those found in normal dogs and in dogs with various infectious diseases. Whole ANAb were detected by immunofluorescence. Anti-double-stranded DNA Ab were found in only 2% of SLE dogs, whereas anti-single-stranded DNA Ab were present in 21.4% of SLE dogs and in 26.8% of dogs with infectious disease. Antihistone Ab were frequently observed in SLE dogs (71%) and are essentially directed against trypsin-resistant epitopes of H3, H4 and H2A. The Western blots of nuclear extracts of HeLa cells were recognized mainly by type 1 Ab (30%, reacting with bands of 43, 36, 35, 34, 30 and 27 kDa) and by anti-Sm Ab (12%) associated with anti-RNP Ab. Anti-SSA and anti-SSB Ab were rare.
Lupus 1992 Oct
PMID:Canine systemic lupus erythematosus. II: Antinuclear antibodies. 128 31


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